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Sadlonova M, Beach SR, Funk MC, Rosen JH, Ramirez Gamero AF, Karlson RA, Huffman JC, Celano CM. Risk Stratification of QTc Prolongation in Critically Ill Patients Receiving Antipsychotics for the Management of Delirium Symptoms. J Intensive Care Med 2025; 40:355-371. [PMID: 38130132 DOI: 10.1177/08850666231222470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]
Abstract
BackgroundPatients experiencing significant agitation or perceptual disturbances related to delirium in an intensive care setting may benefit from short-term treatment with an antipsychotic medication. Some antipsychotic medications may prolong the QTc interval, which increases the risk of potentially fatal ventricular arrhythmias. In this targeted review, we describe the evidence regarding the relationships between antipsychotic medications and QTc prolongation and practical methods for monitoring the QTc interval and mitigating arrhythmia risk.MethodsSearches of PubMed and Cochrane Library were performed to identify studies, published before February 2023, investigating the relationships between antipsychotic medications and QTc prolongation or arrhythmias.ResultsMost antipsychotic medications commonly used for the management of delirium symptoms (eg, intravenous haloperidol, olanzapine, quetiapine) cause a moderate degree of QTc prolongation. Among other antipsychotics, those most likely to cause QTc prolongation are iloperidone and ziprasidone, while aripiprazole and lurasidone appear to have minimal risk for QTc prolongation. Genetic vulnerabilities, female sex, older age, pre-existing cardiovascular disease, electrolyte abnormalities, and non-psychiatric medications also increase the risk of QTc prolongation. For individuals at risk of QTc prolongation, it is essential to measure the QTc interval accurately and consistently and consider medication adjustments if needed.ConclusionsAntipsychotic medications are one of many risk factors for QTc prolongation. When managing agitation related to delirium, it is imperative to assess an individual patient's risk for QTc prolongation and to choose a medication and monitoring strategy commensurate to the risks. In intensive care settings, we recommend regular ECG monitoring, using a linear regression formula to correct for heart rate. If substantial QTc prolongation (eg, QTc > 500 msec) is present, a change in pharmacologic treatment can be considered, though a particular medication may still be warranted if the risks of discontinuation (eg, extreme agitation, removal of invasive monitoring devices) outweigh the risks of arrhythmias.AimsThis review aims to summarize the current literature on relationships between antipsychotic medications and QTc prolongation and to make practical clinical recommendations towards the approach of antipsychotic medication use for the management of delirium-related agitation and perceptual disturbances in intensive care settings.
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Affiliation(s)
- Monika Sadlonova
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
- Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen Medical Center, Göttingen, Germany
- Department of Cardiovascular and Thoracic Surgery, University of Göttingen Medical Center, Göttingen, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany
| | - Scott R Beach
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Margo C Funk
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
- Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA
| | - Jordan H Rosen
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
- Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA
| | - Andres F Ramirez Gamero
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Rebecca A Karlson
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
| | - Jeff C Huffman
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Christopher M Celano
- Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
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Gerentes M, Lajnef M, Szöke A, Aouizerate B, Berna F, Cléry M, Chéreau I, Coulon N, Clauss-Kobayashi J, Fakra E, Dorey JM, Dubertret C, Fond G, Godin O, Goze T, Lançon C, Leboyer M, Leignier S, Llorca PM, Mallet J, Misdrahi D, Oriol N, Rey R, Roux P, Schorr B, Urbach M, Véry E, Schürhoff F, Pignon B. QT Interval, Antipsychotics and Correlates Among Patients with Schizophrenia: Cross-Sectional Data from the Multicentric Real-World FACE-SZ. Drug Saf 2025:10.1007/s40264-025-01526-9. [PMID: 40088341 DOI: 10.1007/s40264-025-01526-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/09/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND The life expectancy of patients with schizophrenia is reduced, partly due to cardiovascular diseases. Antipsychotics are associated with QT interval prolongation, which is a risk factor for arrhythmia and cardiac arrest. The differences between antipsychotic with regard to QT interval prolongation are not well understood. OBJECTIVE The aim was to compare the QT values associated with different antipsychotics within a real-world population of subjects with clinically stable forms of schizophrenia. METHODS The FACE-SZ cohort comprises subjects with psychotic disorders, referred to schizophrenia expert cents. QT interval was measured, as well as all treatments (psychotropic and others). The following maintenance treatment for schizophrenia was analysed cross-sectionally: aripiprazole, clozapine, haloperidol, amisulpride, olanzapine, quetiapine, risperidone. Age, sex, smoking status, body mass index, blood potassium levels, and the co-prescription of another QT-prolonging treatment were used as adjustment factors in multivariable linear regression analyses. RESULTS Among 792 patients, the mean corrected QT (QTc) interval in the sample of patients under monotherapy was 407 ms. The mean age was 31.7 years, and the majority were male (73.3 %). In comparison to the rest of the sample, clozapine was associated with a longer QTc interval (β = 0.012, 95% CI [0.006-0.018]), while aripiprazole was significantly associated with a shorter QTc interval (β = - 0.010, 95% CI [- 0.016 to - 0.005]). Other antipsychotics were not associated with significant variations of the QTc. CONCLUSIONS The prescription of antipsychotics should always be accompanied by close monitoring of the QTc interval to prevent the risk of severe cardiac arrhythmia, particularly concerning clozapine.
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Affiliation(s)
- Mona Gerentes
- FondaMental Foundation, 94010, Créteil, France
- Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires "H. Mondor", DMU IMPACT, INSERM, IMRB, Translational Neuropsychiatry, Créteil, France
| | - Mohamed Lajnef
- FondaMental Foundation, 94010, Créteil, France
- Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires "H. Mondor", DMU IMPACT, INSERM, IMRB, Translational Neuropsychiatry, Créteil, France
| | - Andrei Szöke
- FondaMental Foundation, 94010, Créteil, France
- Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires "H. Mondor", DMU IMPACT, INSERM, IMRB, Translational Neuropsychiatry, Créteil, France
| | - Bruno Aouizerate
- FondaMental Foundation, 94010, Créteil, France
- General and University Psychiatry Department, Charles Perrens Hospital, 33076, Bordeaux, France
- Univ. Bordeaux, CNRS, INCIA, UMR 5287, 33000, Bordeaux, France
| | - Fabrice Berna
- FondaMental Foundation, 94010, Créteil, France
- Department of Psychiatry, University Hospitals of Strasbourg, University of Strasbourg, Inserm U1114, Strasbourg, France
| | - Maud Cléry
- FondaMental Foundation, 94010, Créteil, France
- Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires "H. Mondor", DMU IMPACT, INSERM, IMRB, Translational Neuropsychiatry, Créteil, France
| | - Isabelle Chéreau
- FondaMental Foundation, 94010, Créteil, France
- CHU Clermont-Ferrand, Service of Psychiatry B, University of Clermont Auvergne, Clermont-Ferrand, France
| | - Nathalie Coulon
- FondaMental Foundation, 94010, Créteil, France
- Grenoble Alpes University, Inserm U1216, CHU Grenoble Alpes, Grenoble Institute of Neurosciences, Grenoble, France
| | - Julia Clauss-Kobayashi
- FondaMental Foundation, 94010, Créteil, France
- Department of Psychiatry, University Hospitals of Strasbourg, University of Strasbourg, Inserm U1114, Strasbourg, France
| | - Eric Fakra
- FondaMental Foundation, 94010, Créteil, France
- Department of Psychiatry, University Hospital of Saint-Etienne, Saint-Etienne, France
| | - Jean-Michel Dorey
- FondaMental Foundation, 94010, Créteil, France
- Le Vinatier Hospital, Schizophrenia Expert Centre, 69500, Bron, France
- INSERM, U1028, CNRS, UMR5292, University Lyon 1, Lyon Neuroscience Research Center, PSYR2 Team, 69000, Lyon, France
| | - Caroline Dubertret
- FondaMental Foundation, 94010, Créteil, France
- AP-HP, Department of Psychiatry, Louis Mourier Hospital, Colombes, France
- Inserm UMR1266, Institute of Psychiatry and Neuroscience of Paris, University Paris Descartes, Paris, France
- Université Paris Diderot, Sorbonne Paris Cité, Faculté de médecine, Paris, France
| | - Guillaume Fond
- FondaMental Foundation, 94010, Créteil, France
- APHM, Service de psychiatrie universitaire, Aix-Marseille université, Marseille, France
| | - Ophélia Godin
- FondaMental Foundation, 94010, Créteil, France
- Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires "H. Mondor", DMU IMPACT, INSERM, IMRB, Translational Neuropsychiatry, Créteil, France
| | - Tudi Goze
- FondaMental Foundation, 94010, Créteil, France
- Department of Psychiatry, Psychotherapies, Art-therapy, Toulouse University HospitalEquipe de Recherche sur les Rationalités Philosophiques et les Savoirs-EA3051, Université de Toulouse-Jean Jaurès, Toulouse, France
| | - Christophe Lançon
- FondaMental Foundation, 94010, Créteil, France
- APHM, Service de psychiatrie universitaire, Aix-Marseille université, Marseille, France
| | - Marion Leboyer
- FondaMental Foundation, 94010, Créteil, France
- Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires "H. Mondor", DMU IMPACT, INSERM, IMRB, Translational Neuropsychiatry, Créteil, France
| | - Sylvain Leignier
- FondaMental Foundation, 94010, Créteil, France
- Grenoble Alpes University, Inserm U1216, CHU Grenoble Alpes, Grenoble Institute of Neurosciences, Grenoble, France
| | - Pierre-Michel Llorca
- FondaMental Foundation, 94010, Créteil, France
- CHU Clermont-Ferrand, Service of Psychiatry B, University of Clermont Auvergne, Clermont-Ferrand, France
| | - Jasmina Mallet
- FondaMental Foundation, 94010, Créteil, France
- AP-HP, Department of Psychiatry, Louis Mourier Hospital, Colombes, France
- Inserm UMR1266, Institute of Psychiatry and Neuroscience of Paris, University Paris Descartes, Paris, France
- Université Paris Diderot, Sorbonne Paris Cité, Faculté de médecine, Paris, France
- Department of Psychiatry, Centre Hospitalier Universitaire d'Orléans, EPSM du Loiret, University of Orléans, Centre Hospitalier Universitaire d'Orléans, Orléans, France
| | - David Misdrahi
- FondaMental Foundation, 94010, Créteil, France
- General and University Psychiatry Department, Charles Perrens Hospital, 33076, Bordeaux, France
- Univ. Bordeaux, CNRS, INCIA, UMR 5287, 33000, Bordeaux, France
| | - Nicolas Oriol
- FondaMental Foundation, 94010, Créteil, France
- Department of Psychiatry, University Hospital of Saint-Etienne, Saint-Etienne, France
| | - Romain Rey
- FondaMental Foundation, 94010, Créteil, France
- Le Vinatier Hospital, Schizophrenia Expert Centre, 69500, Bron, France
- INSERM, U1028, CNRS, UMR5292, University Lyon 1, Lyon Neuroscience Research Center, PSYR2 Team, 69000, Lyon, France
| | - Paul Roux
- FondaMental Foundation, 94010, Créteil, France
- Versailles Hospital, Department of Adult Psychiatry and Addictology, Centre Hospitalier de Versailles, Service universitaire de psychiatrie d'adultes et d'addictologie, Le Chesnay, Université Paris-Saclay, Université de Versailles Saint-Quentin-En-Yvelines, DisAP-DevPsy-CESP, INSERM UMR1018, Villejuif, France
| | - Benoit Schorr
- Department of Psychiatry, Psychotherapies, Art-therapy, Toulouse University HospitalEquipe de Recherche sur les Rationalités Philosophiques et les Savoirs-EA3051, Université de Toulouse-Jean Jaurès, Toulouse, France
| | - Mathieu Urbach
- FondaMental Foundation, 94010, Créteil, France
- Versailles Hospital, Department of Adult Psychiatry and Addictology, Centre Hospitalier de Versailles, Service universitaire de psychiatrie d'adultes et d'addictologie, Le Chesnay, Université Paris-Saclay, Université de Versailles Saint-Quentin-En-Yvelines, DisAP-DevPsy-CESP, INSERM UMR1018, Villejuif, France
| | - Etienne Véry
- FondaMental Foundation, 94010, Créteil, France
- Department of Psychiatry, Psychotherapies, Art-therapy, Toulouse University Hospital, ToNIC, Toulouse Neuroimaging Center, INSERM UMR 1214, Toulouse, France
| | - Franck Schürhoff
- FondaMental Foundation, 94010, Créteil, France
- Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires "H. Mondor", DMU IMPACT, INSERM, IMRB, Translational Neuropsychiatry, Créteil, France
| | - Baptiste Pignon
- FondaMental Foundation, 94010, Créteil, France.
- Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires "H. Mondor", DMU IMPACT, INSERM, IMRB, Translational Neuropsychiatry, Créteil, France.
- Hôpital Albert Chenevier, Groupe hospitalier Henri-Mondor, CHU de Créteil, Assistance Publique-Hôpitaux de Paris (AP-HP), 40 rue de Mesly, 94000, Créteil, France.
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He L, Yu W, Song H, Li L, Shen Y, Zhang L, Li H. Comparative risk of QTc prolongation induced by second-generation antipsychotics in the real world: retrospective cohort study based on a hospital information system. BJPsych Open 2025; 11:e42. [PMID: 40059385 PMCID: PMC12001931 DOI: 10.1192/bjo.2024.871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 12/21/2024] [Accepted: 12/24/2024] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Second-generation antipsychotics (SGAs) can cause corrected QT interval (QTc) prolongation as a side-effect. This may limit their clinical use and pose safety concerns for patients. AIMS To analyse the risk of QTc prolongation associated with eight second-generation antipsychotics and observe the timing characteristics of QTc prolongation events and subsequent changes in medication strategies. METHODS Using data from the hospital information system of a large mental health centre, this retrospective cohort study included 5130 patients (median follow-up: 141.2 days) treated between 2007 and 2019. A marginal structural Cox model was used to compare the hazard ratios for QTc prolongation associated with various SGAs. RESULTS The mean age of the cohort was 35.54 years (s.d. = 14.22), and 47.8% (N = 2454) were male. Ziprasidone, amisulpride and olanzapine were the only SGAs associated with QTc prolongation. Ziprasidone presented the highest risk (hazard ratio 1.72, 95% CI: 1.03-2.85, adjusted P = 0.03), followed by amisulpride (hazard ratio 1.56, 95% CI: 1.04-2.34, adjusted P = 0.03) and olanzapine (hazard ratio 1.40, 95% CI: 1.02-1.94, adjusted P = 0.04). CONCLUSION Ziprasidone, amisulpride and olanzapine are associated with increased risk of QTc prolongation. Regular electrocardiogram monitoring is recommended when clinicians prescribe such drugs.
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Affiliation(s)
- Luyao He
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China
| | - Wenjuan Yu
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China
| | - Huiqing Song
- Shanghai Null Hypothesis Information Technology Co. Ltd, Shanghai, China
| | - Lujin Li
- Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yifeng Shen
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China
| | - Lei Zhang
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China
| | - Huafang Li
- Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China
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Guo Z, Zhang Z, Huang W, Xia H, Huang S, Lan X, Ning Y, Zhou Y, Shang D. Interpretation of the pathogenesis and therapeutic mechanisms of first-episode major depressive disorder based on multiple amino acid metabolic pathways: a metabolomics study. Metab Brain Dis 2024; 40:37. [PMID: 39576355 DOI: 10.1007/s11011-024-01427-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 11/01/2024] [Indexed: 11/24/2024]
Abstract
OBJECTIVES Given the unclear etiology and treatment mechanisms of depression, we aim to explore the metabolic differences between patients with major depressive disorder (MDD) and the healthy population, as well as before and after treatment with escitalopram (ESC). METHODS Recruit first-episode drug-naïve MDD (DN-MDD) patients and healthy controls (HCs). Clinical data and serum samples from all subjects were collected at baseline and patients' samples were collected again after ESC monotherapy for four weeks. Perform non-targeted metabolomic analysis and apply MetaboAnalyst 5.0 to identify differential metabolites and execute KEGG pathway enrichment. RESULTS Through metabolomic analysis of serum samples, 904 differential metabolites were identified in the DN-MDD group compared to the HCs, and 455 metabolites in treated patients compared to DN-MDD patients. In the pathway analysis, DN-MDD state regulated functions of histidine, beta-alanine, aspartate, and tryptophan metabolism, while ESC treatment produced an influence on the biological process of aspartate and sphingolipid. CONCLUSION We respectively depicted metabolism-related biomolecular changes in the serum of patients suffering from MDD and undergoing ESC treatment. Multiple amino acid metabolism pathways were adjusted in MDD patients, and levels of aspartate, arginine and sphingolipids were regulated after ESC monotherapy. These biomolecular changes may bring new insights into the biology and treatment of MDD from the perspective of the serum metabolites.
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Affiliation(s)
- Zhihao Guo
- The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou, 510370, China
- Guangzhou Medical University, 1 Xinzao Road, Guangzhou, China
| | - Zi Zhang
- The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou, 510370, China
- Guangzhou Medical University, 1 Xinzao Road, Guangzhou, China
| | - Wanting Huang
- The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou, 510370, China
- Guangzhou Medical University, 1 Xinzao Road, Guangzhou, China
| | - Hui Xia
- The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou, 510370, China
- Guangzhou Medical University, 1 Xinzao Road, Guangzhou, China
| | - Shanqing Huang
- The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou, 510370, China
- Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China
| | - Xiaofeng Lan
- The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou, 510370, China
- Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China
| | - Yuping Ning
- The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou, 510370, China.
- Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China.
| | - Yanling Zhou
- The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou, 510370, China.
- Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China.
| | - Dewei Shang
- The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou, 510370, China.
- Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, China.
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Liu Q, Yuan X, Sheng C, Cai W, Geng X, Liu H, Song S. Effect of long-term use of antipsychotics on the ventricular repolarization index. BMC Psychiatry 2024; 24:505. [PMID: 39014414 PMCID: PMC11250928 DOI: 10.1186/s12888-024-05947-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 07/04/2024] [Indexed: 07/18/2024] Open
Abstract
BACKGROUND The risk of arrhythmia is usually assessed by the length of the corrected QT interval (QTc) when patients use antipsychotics. Prolonged QTc intervals are thought to increase the probability of malignant ventricular arrhythmias, and if we focus only on the QTc interval, we may be influenced by a single factor and make decisions that are not conducive to effective treatment. The index of cardiac electrophysiological balance (iCEB) is considered more valuable than the QTc for predicting drug-induced arrhythmias. It has been used in clinical practice, but no studies have observed changes in this index after the use of antipsychotics. OBJECTIVE To investigate the changes in ventricular repolarization indices and the occurrence of arrhythmias in patients who have been using antipsychotic drugs for a long time, to compare the changes in iCEBc and QTc and to predict abnormal iCEBc values. METHODS Patients with schizophrenia who had been hospitalized for more than 4 years and who were receiving atypical antipsychotics underwent a 12-lead synchronized electrocardiogram (ECG) every 2-4 weeks. The baseline data were measured at admission, defined as the baseline (time0), and the most obvious abnormal changes in ventricular depolarization and repolarization measured every 12 months were one-year follow-up (time1), two-year follow-up (time2), three-year follow-up (time3), and four-year follow-up (time4). Repeated measures analysis of variance was used for comparisons. The types and doses of drugs taken at 5 time points were recorded and converted into chlorpromazine equivalents for comparison. The incidence of arrhythmia during the observation cycle was recorded. RESULTS The patients had been treated with antipsychotic medication for 4 years, and the duration of the QRS wave was longer in males than in females. TpTe, TpTe/QRS, TpTe/QT, TpTe/QTc, iCEB, and iCEBc increased significantly with hospital stay, while TpTe, TpTe/QRS, TpTe/QT, and TpTe/QTc exhibited more obvious changes in these indicators in female patients (P < 0.01). The changes in iCEB and iCEBc were more significant in males (P < 0.01). The incidences of arrhythmia (arrhythmic events included premature ventricular beats and premature atrial beats) within 5 time points were 2.5%, 6.25%, 6.25%, 6.25% and 5%, respectively. More than 90% of patients treated with antipsychotics did not have any arrhythmias. No TdP syncope or other cardiovascular symptoms were found in any of the patients. CONCLUSION After long-term use of antipsychotics, the ventricular repolarization index gradually increased with time. The new ventricular repolarization indices iCEB and iCEBc were more sensitive than the QTc at predicting arrhythmia. According to the abnormal QTc values in men and women, we predict that the abnormal value of the iCEBc in males is 4.528 and that in females is 5.315.
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Affiliation(s)
- Qiong Liu
- Department of ECG Room, Chaohu Hospital of Anhui Medical University, 64 North Chaohu Road, Hefei, 238000, China
| | - Xiaoping Yuan
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, 64 North Chaohu Road, Hefei, 238000, China
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China
| | - Chengdong Sheng
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, 64 North Chaohu Road, Hefei, 238000, China
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China
| | - Weixun Cai
- Heart Center, Department of Electrocardiographic & Cardiac Examination, Zhejiang Provincial People's Hospital(Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, 310000, Zhejiang, China
| | - Xuhong Geng
- Department of Function, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China
| | - Huanzhong Liu
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, 64 North Chaohu Road, Hefei, 238000, China.
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China.
| | - Suqi Song
- Department of Psychiatry, Chaohu Hospital of Anhui Medical University, 64 North Chaohu Road, Hefei, 238000, China.
- Anhui Psychiatric Center, Anhui Medical University, Hefei, 238000, China.
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Sharif AF, Sobh ZK, Abdo SAEF, Alahmadi OM, Alharbi HA, Awaji MS, Alabdullatif FA, Baghlaf AM, Alanazi AF, Fayed MM. Evaluation of Global Dystonia Rating Scale as a predictor of unfavorable outcomes among acute antipsychotics poisoned patients. Drug Chem Toxicol 2024; 47:386-403. [PMID: 38348658 DOI: 10.1080/01480545.2024.2313561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 01/25/2024] [Indexed: 07/02/2024]
Abstract
Worldwide, acute antipsychotic poisoning results in high morbidities and mortalities. Though extrapyramidal syndromes are commonly associated, the extent of extrapyramidal syndromes in relation to the severity of antipsychotic poisoning has not been addressed yet. Thus, this study aimed to assess the Global Dystonia Rating Scale (GDRS) as an unfavorable outcomes predictive tool in acute antipsychotic poisoning. A cross-sectional study included 506 antipsychotic-poisoned patients admitted to Tanta University Poison Control Center, Egypt, over three years was conducted. The mean GDRS was 9.1 ± 16.7 in typical antipsychotic poisoning, which was significantly higher than that of atypical antipsychotics (4.2 ± 11.5) (p = 0.003). Patients with GDRS> 20 showed significantly higher liability for all adverse outcomes (p < 0.05). However, poisoning with typical antipsychotics was associated with significantly more cardiotoxicity (p = 0.042), particularly prolonged QRS (p = 0.005), and intensive care unit (ICU) admission (p = 0.000). In contrary to the PSS, which failed to predict the studied adverse outcomes, GDRS significantly predicted all adverse outcomes (p < 0.000) for all antipsychotic generations. In atypical antipsychotics, GDRS above three accurately predicted cardiotoxicities, prolonged QTc interval, and respiratory failure with Area under curves (AUC) of 0.937, 0.963, and 0.941, respectively. In typical antipsychotic poisoning, at higher cutoffs (7.5, 27.5, 18, and 7.5), cardiotoxicities, prolonged QTc interval, and respiratory failure were accurately predicted (AUC were 0.974, 0.961, and 0.960, respectively). GDRS is an objective, substantially useful tool that quantifies dystonia and can be used as an early reliable predictor of potential toxicity in acute antipsychotic poisoning.
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Affiliation(s)
- Asmaa Fady Sharif
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
- Clinical Medical Sciences Department, College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
| | - Zahraa Khalifa Sobh
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Sanaa Abd El-Fatah Abdo
- Public Health and Community Medicine Department, Faculty of Medicine, Tanta University, Egypt
| | - Osama M Alahmadi
- College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
| | - Hatem A Alharbi
- College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
- Respiratory Care Practitioner, Pediatric Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Mohannad Saif Awaji
- College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
- Emergency Medicine Department, EMS section, King Abdullah Bin Abdulaziz University Hospital, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Faris A Alabdullatif
- College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
- Emergency Operation Center, General Directorate of Health Affairs in Riyadh Region, Ministry of Health, Riyadh, Saudi Arabia
| | | | - Ahmad F Alanazi
- College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
| | - Manar Maher Fayed
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
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Terman SW, Niznik JD, Growdon ME, Gerlach LB, Burke JF. Secular Trends in Central Nervous System-Active Polypharmacy Among Serial Cross-Sections of US Adults, 2009-2020. Drugs Aging 2023; 40:941-951. [PMID: 37695395 PMCID: PMC10629698 DOI: 10.1007/s40266-023-01066-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/27/2023] [Indexed: 09/12/2023]
Abstract
BACKGROUND Data comprehensively examining trends in central nervous system (CNS)-active polypharmacy are limited. The objective of this cross-sectional study was to characterize the composition of and trends in CNS-active medication use in US adults. METHODS We included all participants ≥ 18 years old in the National Health and Nutrition Examination Study (NHANES), 2009-2020. The primary outcome was the percent of adults with CNS-active polypharmacy. This was defined as ≥ 3 medications among antidepressants [tricyclic, selective and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs), opioids, antiepileptics, antipsychotics, benzodiazepines, and nonbenzodiazepine receptor agonists ("Z-drugs")]. Secondary outcomes included prevalence of any CNS-active medication and specific medications and classes over time, and their indications. Percentages were weighted according to NHANES's nationally representative sampling frame. log binomial regressions evaluated the relative risk (RR) for each outcome, comparing the last (2017-2020) versus the first (2010-2011) survey cycle. RESULTS We included 34,189 adults (18.8% at least 65 years old) from five serial cross-sections (survey cycles). The prevalence of CNS-active polypharmacy was 2.1% in 2009-2010 and 2.6% in 2017-2020 [RR 1.18, 95% confidence interval (CI) 0.94-1.47]. The prevalence of CNS-active polypharmacy did not significantly change within any specific age group (e.g., age at least 65 years: RR 1.29, CI 0.74-2.24). The prevalence of any CNS-active medication was 21.0% in 2009 and 24.6% in 2017-2020 (RR] 1.12, 95% CI 1.02-1.25). A substantial increase occurred for antiepileptics (5.1-8.3%), specifically among participants aged 65 years and older (8.3-13.7%). This was largely driven by increasing gabapentin prevalence (1.4-3.6% overall; 3.3-7.9% age 65 years and older). Anticholinergic, SSRIs/SNRIs, antiepileptics, and benzodiazepines were elevated in most cycles for participants at least 65 years old compared with participants less than 65 years, and opioid use was increased in several cycles for older participants as well. Alprazolam was the most common benzodiazepine and third most common medication for anxiety/depression. Gabapentin was the most common CNS-active medication (3.6% of all participants in 2017-2020), followed by sertraline, citalopram, and acetaminophen-hydrocodone (each ~2%). The most common categories were antidepressants (13.7% in 2017-2020), followed by opioids (5.1% in 2017-2020). CONCLUSIONS CNS-active medications are increasingly common, particularly gabapentin, and use of any CNS-active medication increased by 12%. Numerous CNS-active classes also increased in older adults throughout the years. Increasing suboptimal medication use highlight the need for further investigation into causes for potentially inappropriate prescribing, particularly for older adults.
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Affiliation(s)
- Samuel W Terman
- Department of Neurology, University of Michigan, Taubman 1st Floor, Reception C, 1500 E Medical Center Dr, SPC 5316, Ann Arbor, MI, 48109, USA.
| | - Joshua D Niznik
- Division of Geriatric Medicine, Center for Aging and Health, School of Medicine, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA
- Division of Pharmaceutical Outcomes and Policy, Eshelman School of Pharmacy, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA
| | - Matthew E Growdon
- Division of Geriatrics, University of California San Francisco, San Francisco, CA, USA
| | - Lauren B Gerlach
- Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
| | - James F Burke
- Department of Neurology, The Ohio State University, Columbus, OH, USA
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8
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[Effect of the direct healthcare professional communication on citalopram and escitalopram drug utilization for inpatient treatment of anxiety disorders]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2022; 65:1204-1212. [PMID: 36169703 DOI: 10.1007/s00103-022-03594-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 09/05/2022] [Indexed: 11/02/2022]
Abstract
BACKGROUND In 2011, direct healthcare professional communication (DHPC) letters on citalopram and escitalopram were sent out to address the risk of QTc prolongation in the ECG. Healthcare professionals were informed about a reduction of the maximum recommended daily dose. Furthermore, a contraindication for QTc-prolonging co-medication was given. Previous studies noted that these instructions were implemented incompletely. AIM For the first time, this study analyzed how the DHPC affected the prescription of citalopram and escitalopram in patients with anxiety disorders. METHODS Drug utilization data from the project "Arzneimittelsicherheit in der Psychiatrie e. V." (AMSP) was used to examine whether the proportion of patients treated with a higher-than-recommended daily dose ("high dose") and the proportion of patients with QTc-prolonging co-medication would decrease post-DHPC (combined category of citalopram/escitalopram). RESULTS Drug utilization data of n = 364 patients pre- and n = 262 patients post-DHPC were compared. The proportion of patients with high dose declined from 10.7% to 5.4% (p = 0.019). The proportion of patients with QTc-prolonging co-medication did not change significantly from pre- (54.7%) to post-DHPC (51.5%, p = 0.437). DISCUSSION In accordance with previous studies, the proportion of high-dose patients decreased after DHPC publication while the proportion of patients with QTc-prolonging co-medication remained widely unchanged. The specific recommendation on daily dosage seems to have been better implemented than the broadly formulated contraindication of QTc-prolonging co-medication. Hence, DHPCs should be written precisely and give advice for specific clinical situations.
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9
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Cunha AL, Schwartz SE, Cooper JB. Practical Approaches to Antipsychotic-Associated Corrected QT Interval Prolongation in Patients With Serious Mental Illness: A Review of Cases. J Pharm Pract 2022:8971900221078249. [PMID: 35325582 DOI: 10.1177/08971900221078249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND There is no consensus for assessment and management of patients with serious mental illness (SMI) who are at risk for cardiac morbidity and mortality due to antipsychotic-associated QTc prolongation. OBJECTIVE The objective of this review was to assess methods for risk scoring, QT correction calculation, and clinical management in SMI patients with antipsychotic-associated QTc prolongation. METHODS A search was performed in PubMed for case reports that described QTc prolongation in adult patients with schizophrenia or bipolar disorder prescribed an antipsychotic. Reports published in North America between 2000 and 2020 were eligible. The Mayo, Tisdale, and RISQ-PATH scoring tools were applied to cases to categorize risk level. RESULTS Seventeen cases were included. Most patients were prescribed a second-generation antipsychotic for schizophrenia, with baseline and maximum QTc values of 429 milliseconds and 545 milliseconds, respectively. The Mayo scoring tool identified 17 (100%) cases as "high risk," Tisdale identified 9 (53%) cases as "moderate risk" and 7 (41%) cases as "low risk," while RISQ-PATH identified 9 (53%) cases as "not low risk" and 8 (47%) cases as "low risk." Three cases reported the QT correction formula utilized (18%). The most common intervention to address antipsychotic-associated QTc prolongation was switching to a different antipsychotic (35%). Approximately one third of patients experienced Torsades de Pointes. CONCLUSION There is a lack of standardization for antipsychotic-associated QTc prolongation risk assessment and management in patients with SMI. This review provides real-world data representing actual clinical practice.
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Affiliation(s)
- Alexandra L Cunha
- Department of Clinical Sciences, 465018High Point University Fred Wilson School of Pharmacy, High Point, NC, USA
| | - Shaina E Schwartz
- Department of Clinical Sciences, 465018High Point University Fred Wilson School of Pharmacy, High Point, NC, USA
| | - Julie B Cooper
- Department of Clinical Sciences, 465018High Point University Fred Wilson School of Pharmacy, High Point, NC, USA
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10
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Lu Z, Zhang Y, Yan H, Su Y, Guo L, Liao Y, Lu T, Yu H, Wang L, Li J, Li W, Yang Y, Xiao X, Lv L, Tan Y, Zhang D, Yue W. ATAD3B and SKIL polymorphisms associated with antipsychotic-induced QTc interval change in patients with schizophrenia: a genome-wide association study. Transl Psychiatry 2022; 12:56. [PMID: 35136033 PMCID: PMC8825824 DOI: 10.1038/s41398-022-01825-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 01/14/2022] [Accepted: 01/19/2022] [Indexed: 11/26/2022] Open
Abstract
QTc interval prolongation is one of the most common antipsychotic-induced side effects which could lead to ventricular tachycardia or Torsade de Pointes, even cardiac arrest. There is very limited understanding on the genetic factors that associated with antipsychotic-induced QTc interval change. We conducted a genome-wide association study (GWAS) of antipsychotic-induced QTc interval change among patients with schizophrenia. A total of 2040 patients with schizophrenia were randomly assigned to six groups (olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone, and first-generation antipsychotics; first-generation antipsychotics including haloperidol or perphenazine were also assigned randomly) and received 6-week antipsychotic treatment. We identified two novel loci (rs200050752 in ATAD3B and rs186507741 in SKIL) that were associated with antipsychotic-induced QTc interval change at a genome-wide significance level. The combination of polygenic risk score (PRS), based the GWAS of myocardial infarction from BioBank Japan project, and clinical data (sex, heart rate and QTc interval at baseline) could be applied to predict whether patients with schizophrenia have QTc interval prolongation (10 ms was applied as threshold, P < 0.001, area under the curve [AUC] was 0.797), especially for the first episode patients (P < 0.001, AUC was 0.872). We identified two loci located within genes related to mitochondrial function and cell growth and differentiation, which were both associated with schizophrenia and heart function. The combination of PRS and clinical data could predict whether patients with schizophrenia have the side effect of QTc interval prolongation, which could fundamentally guide the choice of antipsychotic in patients with schizophrenia, especially for the first-episode patients.
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Affiliation(s)
- Zhe Lu
- Institute of Mental Health, Peking University Sixth Hospital, Beijing, 100191, China
- National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
- NHC Key Laboratory of Mental Health, & Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder (2018RU006), Chinese Academy of Medical Sciences, Beijing, 100191, China
| | - Yuyanan Zhang
- Institute of Mental Health, Peking University Sixth Hospital, Beijing, 100191, China
- National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
- NHC Key Laboratory of Mental Health, & Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder (2018RU006), Chinese Academy of Medical Sciences, Beijing, 100191, China
| | - Hao Yan
- Institute of Mental Health, Peking University Sixth Hospital, Beijing, 100191, China
- National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
- NHC Key Laboratory of Mental Health, & Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder (2018RU006), Chinese Academy of Medical Sciences, Beijing, 100191, China
| | - Yi Su
- Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, 100096, China
| | - Liangkun Guo
- Institute of Mental Health, Peking University Sixth Hospital, Beijing, 100191, China
- National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
- NHC Key Laboratory of Mental Health, & Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder (2018RU006), Chinese Academy of Medical Sciences, Beijing, 100191, China
| | - Yundan Liao
- Institute of Mental Health, Peking University Sixth Hospital, Beijing, 100191, China
- National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
- NHC Key Laboratory of Mental Health, & Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder (2018RU006), Chinese Academy of Medical Sciences, Beijing, 100191, China
| | - Tianlan Lu
- Institute of Mental Health, Peking University Sixth Hospital, Beijing, 100191, China
- National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
- NHC Key Laboratory of Mental Health, & Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder (2018RU006), Chinese Academy of Medical Sciences, Beijing, 100191, China
| | - Hao Yu
- Department of Psychiatry, Jining Medical University, Jining, Shandong, 272067, China
| | - Lifang Wang
- Institute of Mental Health, Peking University Sixth Hospital, Beijing, 100191, China
- National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
- NHC Key Laboratory of Mental Health, & Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder (2018RU006), Chinese Academy of Medical Sciences, Beijing, 100191, China
| | - Jun Li
- Institute of Mental Health, Peking University Sixth Hospital, Beijing, 100191, China
- National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
- NHC Key Laboratory of Mental Health, & Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder (2018RU006), Chinese Academy of Medical Sciences, Beijing, 100191, China
| | - Wenqiang Li
- Henan Key Lab of Biological Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 435001, China
| | - Yongfeng Yang
- Henan Key Lab of Biological Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 435001, China
| | - Xiao Xiao
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China
| | - Luxian Lv
- Henan Key Lab of Biological Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 435001, China
| | - Yunlong Tan
- Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, 100096, China
| | - Dai Zhang
- Institute of Mental Health, Peking University Sixth Hospital, Beijing, 100191, China
- National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China
- NHC Key Laboratory of Mental Health, & Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder (2018RU006), Chinese Academy of Medical Sciences, Beijing, 100191, China
- PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China
- Chinese Institute for Brain Research, Beijing, 102206, China
| | - Weihua Yue
- Institute of Mental Health, Peking University Sixth Hospital, Beijing, 100191, China.
- National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191, China.
- NHC Key Laboratory of Mental Health, & Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder (2018RU006), Chinese Academy of Medical Sciences, Beijing, 100191, China.
- PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
- Chinese Institute for Brain Research, Beijing, 102206, China.
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Ricci G, Busardò F, Gibelli F, Sirignano A, Brunetti P. Evaluating the risk of toxicity and adverse drug interactions involving recreational GHB use and prescribed drugs. Expert Opin Drug Metab Toxicol 2022; 17:1445-1454. [DOI: 10.1080/17425255.2021.2029404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Giovanna Ricci
- Section of Legal Medicine, School of Law, University of Camerino, Via Andrea D’Accorso 16, 62032 Camerino, Italy
| | - Francesco Busardò
- Unit of Forensic Toxicology, Section of Legal Medicine, Department of Excellence of Biomedical Sciences and Public Health, Marche Polytechnic University of Ancona, Via Tronto 10, 60126 Ancona, Italy
| | - Filippo Gibelli
- Department of Diagnostics and Public Health, Section of Forensic Medicine, University of Verona, Verona, Italy
| | - Ascanio Sirignano
- Section of Legal Medicine, School of Law, University of Camerino, Via Andrea D’Accorso 16, 62032 Camerino, Italy
| | - Pietro Brunetti
- Unit of Forensic Toxicology, Section of Legal Medicine, Department of Excellence of Biomedical Sciences and Public Health, Marche Polytechnic University of Ancona, Via Tronto 10, 60126 Ancona, Italy
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12
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Kahl KG, Stapel B, Correll CU. Psychological and Psychopharmacological Interventions in Psychocardiology. Front Psychiatry 2022; 13:831359. [PMID: 35370809 PMCID: PMC8966219 DOI: 10.3389/fpsyt.2022.831359] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 02/18/2022] [Indexed: 01/08/2023] Open
Abstract
Patients with mental disorders have an increased risk to develop cardiovascular disease (CVD), and CVD are frequently comorbid with especially adjustment, anxiety and depressive disorders. Therefore, clinicians need to be aware of effective and safe psychological and pharmacological treatment strategies for patients with comorbid CVD and mental disorders. Cognitive behavioral therapy and third-wave of cognitive-behavioral therapy are effective for patients with CVD and mental disorders. Internet-based psychological treatments may also be considered. In more severe cases, psychopharmacological drugs are frequently used. Although generally well tolerated and efficacious, drug- and dose-dependent side effects require consideration. Among antidepressants, selective serotonin reuptake inhibitors, selective serotonin and noradrenalin reuptake inhibitors, and newer antidepressants, such as mirtazapine, bupropion, agomelatine, and vortioxetine, can be considered, while tricyclic antidepressants should be avoided due to their cardiac side effects. Mood stabilizers have been associated with arrhythmias, and some first- and second-generation antipsychotics can increase QTc and metabolic side effects, although substantial differences exist between drugs. Benzodiazepines are generally safe in patients with CVD when administered short-term, and may mitigate symptoms of acute coronary syndrome. Laboratory and ECG monitoring is always recommended in psychopharmacological drug-treated patients with CVD. Presence of a heart disease should not exclude patients from necessary interventions, but may require careful risk-benefit evaluations. Effectively and safely addressing mental disorders in patients with CVD helps to improve both conditions. Since CVD increase the risk for mental disorders and vice versa, care providers need to screen for these common comorbidities to comprehensively address the patients' needs.
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Affiliation(s)
- Kai G Kahl
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hanover, Germany
| | - Britta Stapel
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hanover, Germany
| | - Christoph U Correll
- Department of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, United States.,Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States.,Department of Child and Adolescent Psychiatry, Charité - Universitätsmedizin Berlin, Berlin, Germany
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13
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A Real-World Study of Risk Factors for QTc Prolongation in Schizophrenia Patients Receiving Atypical Antipsychotics. J Clin Psychopharmacol 2022; 42:71-74. [PMID: 34928562 DOI: 10.1097/jcp.0000000000001501] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE The risk of sudden cardiac death in patients receiving atypical antipsychotics may be related to QTc prolongation. The aim of this study was to investigate the risk factors for QTc prolongation to prevent QTc prolongation and guide clinical practice. METHODS All electrocardiogram recordings of 913 schizophrenia patients who were receiving atypical antipsychotics were reviewed for prolonged QTc and associated conditions. Binary logistic regression analysis was used to investigate risk factors for QTc prolongation. RESULTS Logistic regression analysis demonstrated that sex (odds ratio [OR], 0.386; P = 0.010), age (OR, 1.047; P = 0.000), high-density lipoprotein (OR, 0.257; P = 0.014), and antipsychotics dose (OR, 1.040; P = 0.036) were significantly associated with QTc prolongation. CONCLUSIONS In patients with male sex, elder age, low high-density lipoprotein, or large antipsychotics dose, QTc should be monitored more frequently.
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14
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Hommers L, Scherf-Clavel M, Stempel R, Roth J, Falter M, Deckert J, Mattheisen M, Unterecker S, Gawlik M. Antipsychotics in routine treatment are minor contributors to QT prolongation compared to genetics and age. J Psychopharmacol 2021; 35:1127-1133. [PMID: 33779379 PMCID: PMC8436313 DOI: 10.1177/02698811211003477] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Drug-induced prolongation of cardiac repolarization limits the treatment with many psychotropic drugs. Recently, the contribution of polygenic variation to the individual duration of the QT interval was identified. AIMS To explore the interaction between antipsychotic drugs and the individual polygenic influence on the QT interval. METHODS Retrospective analysis of clinical and genotype data of 804 psychiatric inpatients diagnosed with a psychotic disorder. The individual polygenic influence on the QT interval was calculated according to the method of Arking et al. RESULTS Linear regression modelling showed a significant association of the individual polygenic QT interval score (ßstd = 0.176, p < 0.001) and age (ßstd = 0.139, p < 0.001) with the QTc interval corrected according to Fridericia's formula. Sex showed a nominal trend towards significance (ßstd = 0.064, p = 0.064). No association was observed for the number of QT prolonging drugs according to AZCERT taken. Subsample analysis (n = 588) showed a significant association of potassium serum concentrations with the QTc interval (ßstd = -0.104, p = 0.010). Haloperidol serum concentrations were associated with the QTc interval only in single medication analysis (n = 26, ßstd = 0.101, p = 0.004), but not in multivariate regression analysis. No association was observed for aripiprazole, clozapine, quetiapine and perazine, while olanzapine and the sum of risperidone and its metabolite showed a negative association. CONCLUSIONS Individual genetic factors and age are main determinants of the QT interval. Antipsychotic drug serum concentrations within the therapeutic range contribute to QTc prolongation on an individual level.
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Affiliation(s)
- Leif Hommers
- Center for Mental Health, University Hospital of Würzburg, Würzburg, Germany
- Interdisciplinary Center for Clinical Research, University Hospital of Würzburg, Würzburg, Germany
- Comprehensive Heart Failure Center (CHFC), University Hospital of Würzburg, Würzburg, Germany
- Leif Hommers, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Margarete-Höppel-Platz 1, Würzburg, 97080, Germany.
| | - Maike Scherf-Clavel
- Center for Mental Health, University Hospital of Würzburg, Würzburg, Germany
| | - Roberta Stempel
- Center for Mental Health, University Hospital of Würzburg, Würzburg, Germany
| | - Julian Roth
- Center for Mental Health, University Hospital of Würzburg, Würzburg, Germany
| | - Matthias Falter
- Center for Mental Health, University Hospital of Würzburg, Würzburg, Germany
| | - Jürgen Deckert
- Center for Mental Health, University Hospital of Würzburg, Würzburg, Germany
| | - Manuel Mattheisen
- Center for Mental Health, University Hospital of Würzburg, Würzburg, Germany
| | - Stefan Unterecker
- Center for Mental Health, University Hospital of Würzburg, Würzburg, Germany
| | - Micha Gawlik
- Center for Mental Health, University Hospital of Würzburg, Würzburg, Germany
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Cao H, Zhou Y, Li T, Yao C, Yang W, Kong S, Wang Y, Yu B, Jiao Q, Sun Y, Jia X, Wang Y, Wang Z, Zhang X, Li J. The Prevalence, Risk Factors and Clinical Correlates of QTc Prolongation in Chinese Hospitalized Patients With Chronic Schizophrenia. Front Psychiatry 2021; 12:704045. [PMID: 34483996 PMCID: PMC8416174 DOI: 10.3389/fpsyt.2021.704045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 07/22/2021] [Indexed: 12/02/2022] Open
Abstract
Background: The QTc interval may be significantly prolonged in schizophrenia patients taking antipsychotics. Few studies have addressed QTc prolongation (QTP) in Chinese patients. Objectives: This study was designed to evaluate the prevalence of QTP and its clinical correlates in Chinese hospitalized patients with chronic schizophrenia. Methods: A total of 436 inpatients and 291 normal controls matched with age and sex were included. QTc prolongation was defined as 2 standard deviations (SD) above the mean value of normal controls. Positive and Negative Syndrome Scale (PANSS) and its five-factor model were used to evaluate psychopathological symptoms. Results: QTc interval was significantly longer in patients than in normal controls. The prevalence of QTP is 8.26% in Chinese hospitalized patients with chronic schizophrenia. More women than men displayed QTP. Compared with patients without QTP, the patients with QTP had significantly higher concrete/disorganized subscore, lower low density lipoprotein (LDL) and lower total protein (TP). Furthermore, binary logistic regression analysis showed that higher number of hospitalizations, higher concrete/disorganized subscore and lower LDL were risk factors for QTP. Correlation analysis indicated significant association between QTc interval and the following variables: sex, age, duration of illness, the number of hospitalizations, PANSS total score, fasting blood glucose (FPG). Finally, a multiple regression analysis showed that older age, antipsychotic polypharmacy, higher PANSS total score, and lower LDL were risk factors for QTP. Among them, LDL seemed to be a protective factor for QTP. Conclusions: QTc interval was longer in schizophrenia patients than in normal controls. The prevalence of QTP is 8.26% in Chinese hospitalized patients with chronic schizophrenia. Some clinical characteristics were risk factors for QTP. And LDL seemed to be a protective factor for QTP.
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Affiliation(s)
- Haiyan Cao
- Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
| | - Yongjie Zhou
- Department of Psychiatric Rehabilitation, Shenzhen Kangning Hospital, Shenzhen, China
| | - Tao Li
- Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
| | - Cong Yao
- Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
| | - Weiliang Yang
- Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
| | - Siying Kong
- Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
| | - Yanyan Wang
- Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
| | - Baoping Yu
- Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
| | - Qingyan Jiao
- Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
| | - Yun Sun
- Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
| | - Xiaoju Jia
- Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
| | - Yuting Wang
- Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
| | - Zhonggang Wang
- Department of Psychiatry, Jining Psychiatric Hospital, Jining, China
| | - Xiangyang Zhang
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
| | - Jie Li
- Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
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16
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Wolff J, Reißner P, Hefner G, Normann C, Kaier K, Binder H, Hiemke C, Toto S, Domschke K, Marschollek M, Klimke A. Pharmacotherapy, drug-drug interactions and potentially inappropriate medication in depressive disorders. PLoS One 2021; 16:e0255192. [PMID: 34293068 PMCID: PMC8297778 DOI: 10.1371/journal.pone.0255192] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 07/11/2021] [Indexed: 12/24/2022] Open
Abstract
Introduction The aim of this study was to describe the number and type of drugs used to treat depressive disorders in inpatient psychiatry and to analyse the determinants of potential drug-drug interactions (pDDI) and potentially inappropriate medication (PIM). Methods Our study was part of a larger pharmacovigilance project funded by the German Innovation Funds. It included all inpatients with a main diagnosis in the group of depressive episodes (F32, ICD-10) or recurrent depressive disorders (F33) discharged from eight psychiatric hospitals in Germany between 1 October 2017 and 30 September 2018 or between 1 January and 31 December 2019. Results The study included 14,418 inpatient cases. The mean number of drugs per day was 3.7 (psychotropic drugs = 1.7; others = 2.0). Thirty-one percent of cases received at least five drugs simultaneously (polypharmacy). Almost one half of all cases received a combination of multiple antidepressant drugs (24.8%, 95% CI 24.1%–25.5%) or a treatment with antidepressant drugs augmented by antipsychotic drugs (21.9%, 95% CI 21.3%–22.6%). The most frequently used antidepressants were selective serotonin reuptake inhibitors, followed by serotonin and norepinephrine reuptake inhibitors and tetracyclic antidepressants. In multivariate analyses, cases with recurrent depressive disorders and cases with severe depression were more likely to receive a combination of multiple antidepressant drugs (Odds ratio recurrent depressive disorder: 1.56, 95% CI 1.41–1.70, severe depression 1.33, 95% CI 1.18–1.48). The risk of any pDDI and PIM in elderly patients increased substantially with each additional drug (Odds Ratio: pDDI 1.32, 95% CI: 1.27–1.38, PIM 1.18, 95% CI: 1.14–1.22) and severity of disease (Odds Ratio per point on CGI-Scale: pDDI 1.29, 95% CI: 1.11–1.46, PIM 1.27, 95% CI: 1.11–1.44), respectively. Conclusion This study identified potential sources and determinants of safety risks in pharmacotherapy of depressive disorders and provided additional data which were previously unavailable. Most inpatients with depressive disorders receive multiple psychotropic and non-psychotropic drugs and pDDI and PIM are relatively frequent. Patients with a high number of different drugs must be intensively monitored in the management of their individual drug-related risk-benefit profiles.
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Affiliation(s)
- Jan Wolff
- Peter L. Reichertz Institute for Medical Informatics of TU Braunschweig and Hannover Medical School, Hannover, Germany
- Faculty of Medicine, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany
- Evangelical Foundation Neuerkerode, Braunschweig, Germany
- * E-mail: ,
| | | | - Gudrun Hefner
- Vitos Clinic for Forensic Psychiatry, Eltville, Germany
| | - Claus Normann
- Faculty of Medicine, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany
| | - Klaus Kaier
- Faculty of Medicine, Institute of Medical Biometry and Statistics, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany
| | - Harald Binder
- Faculty of Medicine, Institute of Medical Biometry and Statistics, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany
| | - Christoph Hiemke
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany
| | - Sermin Toto
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany
| | - Katharina Domschke
- Faculty of Medicine, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany
| | - Michael Marschollek
- Peter L. Reichertz Institute for Medical Informatics of TU Braunschweig and Hannover Medical School, Hannover, Germany
| | - Ansgar Klimke
- Vitos Hochtaunus, Friedrichsdorf, Germany
- Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
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17
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Wolff J, Hefner G, Normann C, Kaier K, Binder H, Hiemke C, Toto S, Domschke K, Marschollek M, Klimke A. Polypharmacy and the risk of drug-drug interactions and potentially inappropriate medications in hospital psychiatry. Pharmacoepidemiol Drug Saf 2021; 30:1258-1268. [PMID: 34146372 DOI: 10.1002/pds.5310] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 05/27/2021] [Accepted: 06/09/2021] [Indexed: 12/28/2022]
Abstract
PURPOSE The aim of this study was to analyze the epidemiology of polypharmacy in hospital psychiatry. Another aim was to investigate predictors of the number of drugs taken and the associated risks of drug-drug interactions and potentially inappropriate medications in the elderly. METHODS Daily prescription data were obtained from a pharmacovigilance project sponsored by the Innovations Funds of the German Federal Joint Committee. RESULTS The study included 47 071 inpatient hospital cases from eight different study centers. The mean number of different drugs during the entire stay was 6.1 (psychotropic drugs = 2.7; others = 3.4). The mean number of drugs per day was 3.8 (psychotropic drugs = 1.6; others = 2.2). One third of cases received at least five different drugs per day on average during their hospital stay (polypharmacy). Fifty-one percent of patients received more than one psychotropic drug simultaneously. Hospital cases with polypharmacy were 18 years older (p < 0.001), more likely to be female (52% vs. 40%, p < 0.001) and had more comorbidities (5 vs. 2, p < 0.001) than hospital cases without polypharmacy. The risks of drug-drug interactions (OR = 3.7; 95% CI = 3.5-3.9) and potentially inappropriate medication use in the elderly (OR = 2.2; CI = 1.9-2.5) substantially increased in patients that received polypharmacy. CONCLUSION Polypharmacy is frequent in clinical care. The number of used drugs is a proven risk factor of adverse drug reactions due to drug-drug interactions and potentially inappropriate medication use in the elderly. The potential interactions and the specific pharmacokinetics and -dynamics of older patients should always be considered when multiple drugs are used.
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Affiliation(s)
- Jan Wolff
- Peter L. Reichertz Institute for Medical Informatics of TU Braunschweig and Hannover Medical School, Hannover, Germany.,Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Evangelical Foundation Neuerkerode, Braunschweig, Germany
| | - Gudrun Hefner
- Vitos Clinic for Forensic Psychiatry, Eltville, Germany
| | - Claus Normann
- Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Klaus Kaier
- Institute of Medical Biometry and Statistics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Harald Binder
- Institute of Medical Biometry and Statistics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Christoph Hiemke
- Department of Psychiatry and Psychotherapy, University Medical Center, Mainz, Germany
| | - Sermin Toto
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany
| | - Katharina Domschke
- Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Michael Marschollek
- Peter L. Reichertz Institute for Medical Informatics of TU Braunschweig and Hannover Medical School, Hannover, Germany
| | - Ansgar Klimke
- Vitos Hochtaunus gemeinnutzige GmbH, Friedrichsdorf, Germany.,Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
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18
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Wolff J, Hefner G, Normann C, Kaier K, Binder H, Domschke K, Hiemke C, Marschollek M, Klimke A. Predicting the risk of drug-drug interactions in psychiatric hospitals: a retrospective longitudinal pharmacovigilance study. BMJ Open 2021; 11:e045276. [PMID: 33837103 PMCID: PMC8043005 DOI: 10.1136/bmjopen-2020-045276] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVES The aim was to use routine data available at a patient's admission to the hospital to predict polypharmacy and drug-drug interactions (DDI) and to evaluate the prediction performance with regard to its usefulness to support the efficient management of benefits and risks of drug prescriptions. DESIGN Retrospective, longitudinal study. SETTING We used data from a large multicentred pharmacovigilance project carried out in eight psychiatric hospitals in Hesse, Germany. PARTICIPANTS Inpatient episodes consecutively discharged between 1 October 2017 and 30 September 2018 (year 1) or 1 January 2019 and 31 December 2019 (year 2). OUTCOME MEASURES The proportion of rightly classified hospital episodes. METHODS We used gradient boosting to predict respective outcomes. We tested the performance of our final models in unseen patients from another calendar year and separated the study sites used for training from the study sites used for performance testing. RESULTS A total of 53 909 episodes were included in the study. The models' performance, as measured by the area under the receiver operating characteristic, was 'excellent' (0.83) and 'acceptable' (0.72) compared with common benchmarks for the prediction of polypharmacy and DDI, respectively. Both models were substantially better than a naive prediction based solely on basic diagnostic grouping. CONCLUSION This study has shown that polypharmacy and DDI can be predicted from routine data at patient admission. These predictions could support an efficient management of benefits and risks of hospital prescriptions, for instance by including pharmaceutical supervision early after admission for patients at risk before pharmacological treatment is established.
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Affiliation(s)
- Jan Wolff
- Peter L. Reichertz Institute for Medical Informatics, Hannover Medical School, Hannover, Germany
- Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Freiburg, Germany
| | - Gudrun Hefner
- Vitos Clinic for Forensic Psychiatry, Vitos Rheingau, Eltville, Germany
| | - Claus Normann
- Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Freiburg, Germany
| | - Klaus Kaier
- Institute for Medical Biometry and Statistics, Medical Center-University of Freiburg, Freiburg, Germany
| | - Harald Binder
- Institute for Medical Biometry and Statistics, Medical Center-University of Freiburg, Freiburg, Germany
| | - Katharina Domschke
- Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Freiburg, Germany
| | - Christoph Hiemke
- Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany
| | - Michael Marschollek
- Peter L. Reichertz Institute for Medical Informatics, Hannover Medical School, Hannover, Germany
| | - Ansgar Klimke
- Waldkrankenhaus Köppern, Vitos Hospital Hochtaunus, Friedrichsdorf, Germany
- Department of Psychiatry and Psychotherapy, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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19
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Hallett N, Duxbury J, McKee T, Harrison N, Haines A, Craig E, O'Brien AJ. Taser use on individuals experiencing mental distress: An integrative literature review. J Psychiatr Ment Health Nurs 2021; 28:56-71. [PMID: 31957217 DOI: 10.1111/jpm.12594] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 12/25/2019] [Accepted: 01/13/2020] [Indexed: 11/28/2022]
Abstract
WHAT IS KNOWN ABOUT THE SUBJECT?: People experiencing mental distress have a high rate of contact with police in community crisis events. Police use a continuum of responses when managing situations involving agitation, aggression and behavioural problems. People experiencing mental distress have been subjected to Tasers as part of the police response. Following a number of deaths and numerous reports of injuries, concerns have been raised about the safety of Tasers. WHAT THIS PAPER ADDS?: Police use of Tasers in mental health crises is relatively common. Tasers are used in a range of settings including public places, private residences and healthcare facilities. People experiencing mental distress may be subjected to more use of Tasers than the general population. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health professionals need to work with police towards greater understanding of the needs of people experiencing mental distress and to promote the use of non-coercive interventions in mental health crisis events. Mental health researchers need to explore the qualitative experiences of people who are Tasered, to provide an evidence base for Taser use with people experiencing mental distress. ABSTRACT: Introduction Conducted electrical weapons, or "Tasers," are currently used by over 15,000 law enforcement and military agencies worldwide. There are concerns regarding the effectiveness, potential for harm and overuse with people experiencing mental distress. Aim To explore the literature about police use of Tasers with people experiencing mental distress. Method An integrative review was undertaken, and qualitative and quantitative analytical approaches were used. Results Thirty-one studies were included. Of all recorded usage, overall prevalence of Taser use on people experiencing mental distress was 28%. This population appears to experience higher Taser usage than the general population. Discussion There are substantial gaps in the research literature particularly with respect to the decision-making processes involved in deploying Tasers on this population and the physical and psychological consequences of Taser use in this context. Implications for practice Police use of Tasers in mental health crises is relatively common and occurs in a variety of environments including mental health settings. Mental health professionals need to work with police towards greater understanding of the needs of people with mental illness and to promote the use of non-coercive interventions in mental health crisis events.
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Affiliation(s)
- Nutmeg Hallett
- Department of Nursing, Manchester Metropolitan University, Manchester, UK
| | - Joy Duxbury
- Department of Nursing, Manchester Metropolitan University, Manchester, UK
| | - Tina McKee
- Lancashire School of Law and Social Sciences, University of Central Lancashire, Lancashire, UK
| | - Natalie Harrison
- Department of Psychology, Birmingham City University, Birmingham, UK
| | - Alina Haines
- Department of Nursing, Manchester Metropolitan University, Manchester, UK
| | - Elaine Craig
- Department of Nursing, Manchester Metropolitan University, Manchester, UK
| | - Anthony J O'Brien
- Auckland District Health Board, University of Auckland, Auckland, New Zealand
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20
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Kamath A, Rai KM, Shreyas R, Saxena PUP, Banerjee S. Effect of domperidone, ondansetron, olanzapine-containing antiemetic regimen on QT C interval in patients with malignancy: a prospective, observational, single-group, assessor-blinded study. Sci Rep 2021; 11:445. [PMID: 33431995 PMCID: PMC7801395 DOI: 10.1038/s41598-020-79380-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 12/07/2020] [Indexed: 02/08/2023] Open
Abstract
Domperidone, ondansetron and olanzapine can prolong the QT interval. The clinical use of combinations of these drugs is not uncommon. Our study aimed to determine the presence of any QTc prolonging effect of the combination when used as antiemetic in patients receiving cancer chemotherapy. We carried out a prospective, observational study of patients with malignancy who were to receive domperidone, ondansetron and olanzapine-containing antiemetic regimen. Electrocardiograms were recorded before and during the administration of antiemetics, for three consecutive days. A blinded assessor determined the QTc interval using Bazett and Fridericia formulae. Thirty-six patients completed the study; 23 (63.9%) were females. There was a statistically significant change in QTc with time (Fridericia, χ2(4) = 15.629, p = 0.004; Bazett, χ2(4) = 15.910, p = 0.003); QTc on Day 1 was more than that during baseline (p < 0.001); these differences were significant in females (Fridericia, χ2(4) = 13.753, p = 0.008; Bazett, χ2 (4) = 13.278, p = 0.010) but not in males (Fridericia, χ2 (4) = 4.419, p = 0.352; Bazett, χ2(4) = 4.280, p = 0.369). Two female patients had an absolute QTc prolongation (Bazett correction) of > 500 ms. However, no clinically significant adverse events occurred. The findings show that QTc prolongation is a concern with olanzapine alone and in combination with domperidone and ondansetron, and needs to be investigated further.
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Affiliation(s)
- Ashwin Kamath
- Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, 575001, India
| | - K Maneesh Rai
- Department of Cardiology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, 575001, India
| | - R Shreyas
- Department of Radiation Oncology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, 575001, India
| | - P U Prakash Saxena
- Department of Radiation Oncology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, 575001, India.
| | - Sourjya Banerjee
- Department of Radiation Oncology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka, 575001, India
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21
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Hefner G, Hahn M, Hiemke C, Toto S, Wolff J, Roll SC, Klimke A. Pharmacodynamic Drug-Drug interactions of QT-prolonging drugs in hospitalized psychiatric patients. J Neural Transm (Vienna) 2021; 128:243-252. [PMID: 33417009 DOI: 10.1007/s00702-020-02291-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 12/14/2020] [Indexed: 12/30/2022]
Abstract
At least 170 approved drugs are linked to QT prolongation, which can lead to serious adverse drug reactions (ADRs), such as Torsade de Pointes (TdP). The aim of this study was to analyze the prevalence and type of pharmacodynamic drug-drug interactions (DDIs) between QT-prolonging drugs in psychiatry. The present retrospective analysis used data from a large pharmacovigilance study, conducted in 10 psychiatric hospitals in Germany. Patients medication lists were screened for QT-prolonging drugs, classified according to the Arizona Center for Education and Research on Therapeutics (AZCERT). In total, 27,396 patient cases (46% female) with a mean (± standard deviation) age of 47 ± 18 years were included in the study. Altogether, 83% of the cases received at least one and up to eight QT-prolonging drugs at the same time. Combination of drugs with a known or possible risk for TdP (according to the AZCERT) was detected in 13,670 cases (50%). Most frequently prescribed psychotropic high-risk drugs (n = 48,995) were the antipsychotics pipamperone (n = 6202), quetiapine (n = 5718), prothipendyl (n = 4298), and risperidone (n = 4265). The replacement of high-risk drugs such as tricyclic antidepressants, levomepromazine, melperone, and promethazine with more tolerable drugs could avoid 11% of QT-prolonging drugs and increase the tolerability of psychopharmacological treatment. More than 80% of psychiatric patients receive at least one QT-prolonging drug during their hospital stay, and almost 50% of these drugs are combined in clinical practice. For the prevention of cardiac ADRs, the physician should evaluate the risk for QT prolongation for each drug and patient-specific risk factors before prescribing these drugs or drug combinations.
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Affiliation(s)
- Gudrun Hefner
- Department of Psychiatry and Psychotherapy, Vitos Klinikum Hochtaunus, Emil-Sioli-Weg 1-3, 61081, Friedrichsdorf, Germany.
| | - Martina Hahn
- Psychiatric Hospital, Vitos Klinik Eichberg, Eltville, Germany
| | - Christoph Hiemke
- Department of Psychiatry and Psychotherapy, University Medical Center of Mainz, Mainz, Germany
| | - Sermin Toto
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany
| | - Jan Wolff
- Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Evangelical Foundation Neuerkerode, Braunschweig, Germany
| | - Sibylle C Roll
- Psychiatric Hospital, Vitos Klinik Eichberg, Eltville, Germany
| | - Ansgar Klimke
- Department of Psychiatry and Psychotherapy, Vitos Klinikum Hochtaunus, Emil-Sioli-Weg 1-3, 61081, Friedrichsdorf, Germany.,Heinrich-Heine-University, Duesseldorf, Germany
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22
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Yoshida K, Takeuchi H. Dose-dependent effects of antipsychotics on efficacy and adverse effects in schizophrenia. Behav Brain Res 2021; 402:113098. [PMID: 33417992 DOI: 10.1016/j.bbr.2020.113098] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 12/02/2020] [Accepted: 12/23/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Antipsychotics are a cornerstone of pharmacological treatment of schizophrenia. Improved understanding of the dose-response relationship of antipsychotics in terms of efficacy, adverse effects, and mortality can help to optimize the pharmacological treatment of schizophrenia. METHODS This narrative literature review summarizes current evidence on the relationship of antipsychotic dose with efficacy, adverse effects, and mortality in patients with schizophrenia. RESULTS The efficacy of antipsychotics generally appeared to be highly dose-dependent in the acute phase of schizophrenia, with each antipsychotic having a specific dose-response curve. The presence or absence of dose-dependency and its extent varied according to the type of adverse effect. Parkinsonism, hyperprolactinemia, weight gain, and neurocognitive impairment appeared to be dose-related. The following adverse effects might be at least somewhat dose-dependent: akathisia, tardive dyskinesia, osteoporosis, sexual dysfunction, diabetes mellitus, myocardial infarction, stroke, thromboembolism, QT interval prolongation, anticholinergic adverse effects, somnolence, pneumonia, hip fracture, and neuroleptic malignant syndrome. In contrast, the relationships of antipsychotic dose with dyslipidemia, hypotension, seizure, sialorrhea, and neutropenia and agranulocytosis remained unclear due to mixed findings and/or limited data. Although a higher lifetime cumulative antipsychotic dose might contribute to higher mortality, it is still difficult to conclude whether mortality increases in a dose-dependent manner. CONCLUSION These findings could help clinicians to optimize antipsychotic treatment in patients with schizophrenia by balancing risks and benefits in clinical practice. However, further investigations with larger sample sizes and more robust study designs that focus on each antipsychotic agent are needed.
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Affiliation(s)
- Kazunari Yoshida
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Pharmacogenetics Research Clinic, Centre for Addiction and Mental Health, Toronto, ON, Canada; Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Hiroyoshi Takeuchi
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
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23
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Elgazzar FM, Elgohary MS, Basiouny SM, Lashin HI. Intravenous lipid emulsion as an adjuvant therapy of acute clozapine poisoning. Hum Exp Toxicol 2021; 40:1053-1063. [DOI: 10.1177/0960327120983873] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Introduction: Clozapine is a frequently prescribed atypical antipsychotic drug. Various case reports documented the successful recovery of acute antipsychotics toxicity in association with the administration of intralipid emulsion (ILE). Aim: This study aimed to assess the adjuvant therapeutic role of SMOF Lipid administration on the outcomes of acute clozapine poisoning. Methods: Forty patients with acute clozapine poisoning were randomly allocated into two equal groups. The control group received the standard supportive treatment only, whereas the intervention group received the standard supportive treatment plus SMOF Lipid 20% infusion. All patients were subjected to history taking, full clinical examination, and laboratory investigations. The study outcomes were evaluated. Results: The mean Glasgow Coma Scale (GCS) at 6 hours (13.1 ± 2.3 vs 9.2 ± 2, p < 0.001) and 12 hours (14.3 ± 1.5 vs 9.6 ± 2, p < 0.001) after admission was significantly higher in the intervention group compared to the control group. The intervention group showed a significantly lower frequency of prolonged QTc interval 12 hours after admission (p = 0.003), as well as a significantly shorter hospital stay (p < 0.001). Conclusions: SMOF Lipid infusion seemed to have improved GCS, the prolonged QTc interval, and shortened the length of hospital stay. Furthermore, there were no adverse effects related to its administration.
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Affiliation(s)
- Fatma M Elgazzar
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Mona S Elgohary
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Sara M Basiouny
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Heba I Lashin
- Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
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24
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Abstract
Effective pharmacological and psychotherapeutic treatments are well established for obsessive-compulsive disorder (OCD). Serotonin reuptake inhibitors (SRIs) are first-line treatment and are of benefit to about half of patients. Augmentation of SRI treatment with low-dose neuroleptics is an evidence-based second-line strategy. Specialty psychotherapy is also used as both first-line and second-line treatment and can benefit many. However, a substantial number of patients do not respond to these treatments. New alternatives are urgently needed. This review summarizes evidence for these established pharmacotherapeutic strategies, and for others that have been investigated in refractory disease but are not supported by the same level of evidence. We focus on three neurotransmitter systems in the brain: serotonin, dopamine, and glutamate. We summarize evidence from genetic, neuroimaging, animal model, and other lines of investigation that probe these three systems in patients with OCD. We also review recent work on predictors of response to current treatments. While many studies suggest abnormalities that may provide insight into the pathophysiology of the disorder, most studies have been small, and non-replication of reported findings has been common. Nevertheless, the gradual accrual of evidence for neurotransmitter dysregulation may in time lead the way to new pharmacological strategies.
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25
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Noel JM, Jackson CW. ASHP Therapeutic Position Statement on the Use of Antipsychotic Medications in the Treatment of Adults with Schizophrenia and Schizoaffective Disorder. Am J Health Syst Pharm 2020; 77:2114-2132. [PMID: 32871013 PMCID: PMC7499485 DOI: 10.1093/ajhp/zxaa303] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
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Affiliation(s)
- Jason M Noel
- University of Maryland School of Pharmacy, Baltimore, MD
| | - Cherry W Jackson
- Auburn University Harrison School of Pharmacy, Auburn, AL.,Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, School of Medicine, Birmingham, AL
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26
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Clinically Relevant Interactions between Atypical Antipsychotics and Anti-Infective Agents. Pharmaceuticals (Basel) 2020; 13:ph13120439. [PMID: 33276675 PMCID: PMC7761579 DOI: 10.3390/ph13120439] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 11/23/2020] [Accepted: 11/30/2020] [Indexed: 12/11/2022] Open
Abstract
This is a comprehensive review of the literature on drug interactions (DIs) between atypical antipsychotics and anti-infective agents that focuses on those DIs with the potential to be clinically relevant and classifies them as pharmacokinetic (PK) or pharmacodynamic (PD) DIs. PubMed searches were conducted for each of the atypical antipsychotics and most commonly used anti-infective agents (13 atypical antipsychotics by 61 anti-infective agents/classes leading to 793 individual searches). Additional relevant articles were obtained from citations and from prior review articles written by the authors. Based on prior DI articles and our current understanding of PK and PD mechanism, we developed tables with practical recommendations for clinicians for: antibiotic DIs, antitubercular DIs, antifungal DIs, antiviral DIs, and other anti-infective DIs. Another table reflects that in clinical practice, DIs between atypical antipsychotics and anti-infective agents occur in patients also suffering an infection that may also influence the PK and PD mechanisms of both drugs (the atypical antipsychotic and the anti-infective agent(s)). These tables reflect the currently available literature and our current knowledge of the field and will need to be updated as new DI information becomes available.
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Ostuzzi G, Papola D, Gastaldon C, Schoretsanitis G, Bertolini F, Amaddeo F, Cuomo A, Emsley R, Fagiolini A, Imperadore G, Kishimoto T, Michencigh G, Nosé M, Purgato M, Serdar D, Stubbs B, Taylor D, Thornicroft G, Ward PB, Hiemke C, Correll CU, Barbui C. Safety of Psychotropic Medications in People With COVID-19: Evidence Review and Practical Recommendations. FOCUS: JOURNAL OF LIFE LONG LEARNING IN PSYCHIATRY 2020; 18:466-481. [PMID: 33343260 DOI: 10.1176/appi.focus.18308] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
(Reprinted with permission from the BMC Medicine (2020) 18:215).
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Anmella G, Arbelo N, Fico G, Murru A, Llach CD, Madero S, Gomes-da-Costa S, Imaz ML, López-Pelayo H, Vieta E, Pintor L. COVID-19 inpatients with psychiatric disorders: Real-world clinical recommendations from an expert team in consultation-liaison psychiatry. J Affect Disord 2020; 274:1062-1067. [PMID: 32663933 PMCID: PMC7836977 DOI: 10.1016/j.jad.2020.05.149] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 05/20/2020] [Accepted: 05/22/2020] [Indexed: 01/25/2023]
Abstract
BACKGROUND The management of coronavirus disease 2019 (COVID-19) in patients with comorbid psychiatric disorders poses several challenges, especially regarding drug interactions. METHODS We report three representative case-scenarios on patients with psychiatric disorders and COVID-19 to provide a practical approach based on the existing literature and the clinical experience of an expert team in consultation-liaison psychiatry. CASE-CENTERED RECOMMENDATIONS Psychopharmacological ongoing treatments should be prioritized and most doses should be reduced 25-50% of original dose if the patient receives lopinavir/ritonavir, with some exceptions including quetiapine, asenapine, olanzapine, sertraline, lamotrigine, bupropion, and methadone. If the psychopharmacological usual doses are in the low-to-median range levels, a dose change during COVID-19 drugs co-administration is not recommended, but only ECG and clinical monitoring of adverse effects and drug levels if required. Furthermore, when introducing a psychopharmacological drug, dose titration should be progressive, with ECG monitoring if cardiotoxic interactions are present. (A) In agitated delirium, olanzapine is recommended as first-line antipsychotic and quetiapine should be avoided. (B) In severe mental illness (SMI), essential treatments should be maintained. (C) In non-SMI with depressive/anxiety symptoms, psychological support should be provided and symptoms identified and treated. LIMITATIONS Most recommendations on pharmacological interactions provide only a limited qualitative approach and quantitative recommendations are lacking. CONCLUSIONS Patients with psychiatric disorders and COVID-19 should be managed on a personalized basis considering several clinical criteria and, should not be excluded from receiving COVID-19 treatments. Risks of pharmacological interaction are not absolute and should be contextualized, and most psychopharmacological treatments should include an ECG with special attention to QTc interval.
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Affiliation(s)
- G Anmella
- Consultation Liaison Psychiatry Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain; Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain
| | - N Arbelo
- Consultation Liaison Psychiatry Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain
| | - G Fico
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain
| | - A Murru
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain
| | - C D Llach
- Consultation Liaison Psychiatry Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain
| | - S Madero
- Consultation Liaison Psychiatry Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain
| | - S Gomes-da-Costa
- Consultation Liaison Psychiatry Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain; Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain
| | - M L Imaz
- Consultation Liaison Psychiatry Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain
| | - H López-Pelayo
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain; GRAC, Addictions Unit, Department of Psychiatry, Clinical Institute of Neuroscience, Hospital Clínic, IDIBAPS, RETICS (Red de Trastornos adictivos), University of Barcelona, Villarroel, 170, 08036 Barcelona, Spain
| | - E Vieta
- Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain
| | - L Pintor
- Consultation Liaison Psychiatry Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain.
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Malone K, Hancox JC. QT interval prolongation and Torsades de Pointes with donepezil, rivastigmine and galantamine. Ther Adv Drug Saf 2020; 11:2042098620942416. [PMID: 32874532 PMCID: PMC7436781 DOI: 10.1177/2042098620942416] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 06/19/2020] [Indexed: 01/08/2023] Open
Abstract
Background Acetylcholinesterase inhibitors (AChEis) including donepezil, galantamine and rivastigmine are used to treat Alzheimer's disease (AD). This study aimed to evaluate evidence from the case report literature for an association between these agents and risk of QT interval prolongation and Torsades de Pointes (TdP) arrhythmia. Methods Published literature was mined with predetermined MeSH terms for each of donepezil, galantamine and rivastigmine, to identify cases of QT interval prolongation and TdP. Case reports were analysed using causality scales and a QT interval nomogram. Results A total of 13 case reports were found (10 for donepezil, 2 for galantamine and 1 for rivastigmine) with rate corrected QT interval (QTc) prolongation. Five cases with donepezil exhibited TdP. TdP was not reported in the cases with galantamine and rivastigmine. The use of a QT heart rate nomogram highlighted risk with donepezil compared with the other two drugs and the application of the Naranjo causality scale suggested probable or possible causation for all donepezil cases. All patients had at least two other risk factors for TdP, including modifiable risk factors such as electrolyte disturbances, bradycardia, co-administration of QT prolonging drugs. A number of recent cases involved recent changes in medication. Conclusion Our evaluation of the case report literature suggests that there is evidence for a causal association between donepezil and QTc/TdP risk. Attention to risk factors for QTc prolongation/TdP should be exercised when prescribing donepezil and modifiable risk factors corrected. Owing to the low number of cases with galantamine and rivastigmine, further work is needed to establish whether these drugs may be more suitable than donepezil for patients with other risk factors for TdP.
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Affiliation(s)
- Katie Malone
- School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Bristol, UK
| | - Jules C Hancox
- School of Physiology, Pharmacology and Neuroscience, University of Bristol, University Walk, Biomedical Sciences Building, Bristol, BS8 1TD, UK
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Xiong GL, Pinkhasov A, Mangal JP, Huang H, Rado J, Gagliardi J, Demoss D, Karol D, Suo S, Lang M, Stern M, Spearman EV, Onate J, Annamalai A, Saliba Z, Heinrich T, Fiedorowicz JG. QTc monitoring in adults with medical and psychiatric comorbidities: Expert consensus from the Association of Medicine and Psychiatry. J Psychosom Res 2020; 135:110138. [PMID: 32442893 DOI: 10.1016/j.jpsychores.2020.110138] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 04/30/2020] [Accepted: 05/07/2020] [Indexed: 01/08/2023]
Abstract
OBJECTIVE Several psychiatric medications have the potential to prolong the QTc interval and subsequently increase the risk for ventricular arrhythmias such as torsades de pointes (TdP). There is limited guidance for clinicians to balance the risks and benefits of treatments. METHODS After a review of the existing literature, clinical-educators from the Association of Medicine and Psychiatry developed expert consensus guidelines for ECG monitoring of the QTc interval for patients with medical and psychiatric comorbidities who are prescribed medications with the potential to prolong the QTc interval. A risk score was developed based on risk factors for QTc prolongation to guide clinical decision-making. RESULTS A baseline ECG may not be necessary for individuals at low risk for arrythmia. Those individuals with a risk score of two or more should have an ECG prior to the start of a potentially QTc-prolonging medication or be started on a lower risk agent. Antipsychotics are not equivalent in causing QTc prolongation. A consensus-based algorithm is presented for the management of those identified at high (QTc >500 msec), intermediate (males with QTc 450-499 msec or females with QTc > 470-499 msec), or low risk. CONCLUSIONS The proposed algorithm can help clinicians in determining whether ECG monitoring should be considered for a given patient. These guidelines preserve a role for clinical judgment in selection of treatments that balance the risks and benefits, which may be particularly relevant for complex patients with medical and psychiatric comorbidities. Additional studies are needed to determine whether baseline and serial ECG monitoring reduces mortality.
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Affiliation(s)
- Glen L Xiong
- Department of Psychiatry and Behavioral Sciences, University of California at Davis School of Medicine, Sacramento, CA, United States of America.
| | - Aaron Pinkhasov
- Department of Behavioral Health, NYU Winthrop Hospital, Mineola, NY, United States of America
| | - Jed P Mangal
- Department of Behavioral Health, Martin Army Community Hospital, Ft Benning, GA, United States of America
| | - Heather Huang
- Departments of Psychiatry and Internal Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States of America
| | - Jeffrey Rado
- Psychiatry and General Internal Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
| | - Jane Gagliardi
- Departments of Psychiatry and Behavioral Sciences, and Internal Medicine, Duke University School of Medicine, Durham, NC, United States of America
| | - Dustin Demoss
- Department of Psychiatry, University of North Texas Health Science Center, United States of America
| | - David Karol
- Department of Psychiatry and Behavioral Neuroscience, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America
| | - Shannon Suo
- Department of Psychiatry and Behavioral Sciences, University of California at Davis School of Medicine, Sacramento, CA, United States of America
| | - Michael Lang
- Departments of Psychiatry and Internal Medicine, East Carolina University, Greenville, NC, United States of America
| | - Marsha Stern
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States of America
| | - E Vanessa Spearman
- Departments of Internal Medicine and Psychiatry, Medical College of Georgia at Augusta University Medical Center, Augusta, GA, United States of America
| | - John Onate
- Department of Psychiatry and Behavioral Sciences, University of California at Davis School of Medicine, Sacramento, CA, United States of America
| | - Aniyizhai Annamalai
- Departments of Psychiatry and Internal Medicine, Yale School of Medicine, New Haven, CT, United States of America
| | - Zeina Saliba
- Department of Psychiatry & Behavioral Sciences and Department of Emergency Medicine, The George Washington University, Washington, D.C, Department of Obstetrics & Gynecology, Virginia Commonwealth University, Richmond, VA, United States of America
| | - Thomas Heinrich
- Departments of Psychiatry and Behavioral Medicine, Family and Community Medicine, Medical College of Wisconsin, Milwaukee, WI, United States of America
| | - Jess G Fiedorowicz
- Departments of Psychiatry, Epidemiology, and Internal Medicine, University of Iowa, Iowa City, IA, United States of America
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Ostuzzi G, Papola D, Gastaldon C, Schoretsanitis G, Bertolini F, Amaddeo F, Cuomo A, Emsley R, Fagiolini A, Imperadore G, Kishimoto T, Michencigh G, Nosé M, Purgato M, Dursun S, Stubbs B, Taylor D, Thornicroft G, Ward PB, Hiemke C, Correll CU, Barbui C. Safety of psychotropic medications in people with COVID-19: evidence review and practical recommendations. BMC Med 2020; 18:215. [PMID: 32664944 PMCID: PMC7360478 DOI: 10.1186/s12916-020-01685-9] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 06/28/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The novel coronavirus pandemic calls for a rapid adaptation of conventional medical practices to meet the evolving needs of such vulnerable patients. People with coronavirus disease (COVID-19) may frequently require treatment with psychotropic medications, but are at the same time at higher risk for safety issues because of the complex underlying medical condition and the potential interaction with medical treatments. METHODS In order to produce evidence-based practical recommendations on the optimal management of psychotropic medications in people with COVID-19, an international, multi-disciplinary working group was established. The methodology of the WHO Rapid Advice Guidelines in the context of a public health emergency and the principles of the AGREE statement were followed. Available evidence informing on the risk of respiratory, cardiovascular, infective, hemostatic, and consciousness alterations related to the use of psychotropic medications, and drug-drug interactions between psychotropic and medical treatments used in people with COVID-19, was reviewed and discussed by the working group. RESULTS All classes of psychotropic medications showed potentially relevant safety risks for people with COVID-19. A set of practical recommendations was drawn in order to inform frontline clinicians on the assessment of the anticipated risk of psychotropic-related unfavorable events, and the possible actions to take in order to effectively manage this risk, such as when it is appropriate to avoid, withdraw, switch, or adjust the dose of the medication. CONCLUSIONS The present evidence-based recommendations will improve the quality of psychiatric care in people with COVID-19, allowing an appropriate management of the medical condition without worsening the psychiatric condition and vice versa.
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Affiliation(s)
- Giovanni Ostuzzi
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy.
| | - Davide Papola
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
| | - Chiara Gastaldon
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
| | - Georgios Schoretsanitis
- Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA
| | - Federico Bertolini
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
| | - Francesco Amaddeo
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
| | - Alessandro Cuomo
- Department of Molecular Medicine, University of Siena, Siena, Italy
| | - Robin Emsley
- Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Campus, Cape Town, 8000, South Africa
| | - Andrea Fagiolini
- Department of Molecular Medicine, University of Siena, Siena, Italy
| | | | - Taishiro Kishimoto
- Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
| | - Giulia Michencigh
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
| | - Michela Nosé
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
| | - Marianna Purgato
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
| | - Serdar Dursun
- Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada
| | - Brendon Stubbs
- Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK
- Physiotherapy Department, South London and Maudsley National Health Services Foundation Trust, London, UK
| | - David Taylor
- Pharmacy Department, Maudsley Hospital, London, UK
| | - Graham Thornicroft
- Centre for Global Mental Health and Centre for Implementation Science, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Philip B Ward
- School of Psychiatry, UNSW Sydney and Schizophrenia Research Unit, Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia
| | - Christoph Hiemke
- Department of Psychiatry and Psychotherapy, University Medical Center of Mainz, Mainz, Germany
| | - Christoph U Correll
- Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA
- Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Corrado Barbui
- WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy
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Høimark L, Uhrskov Sørensen L, Vukelic Andersen L. Plasma concentrations of antipsychotics and QTc prolongation: a pilot study. Nord J Psychiatry 2020; 74:374-379. [PMID: 32105154 DOI: 10.1080/08039488.2020.1729857] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Background: Certain antipsychotics are known to cause QTc interval prolongation, which has been associated with increased risk of arrhythmia and sudden death. Previous studies have investigated whether there is an association between oral antipsychotic dose and QTc interval prolongation, however only few have examined the association between antipsychotic plasma concentrations and QTc interval.Material and methods: We performed a cross-sectional study with 22 forensic psychiatric in-patients. We measured the plasma concentration of the prescribed antipsychotics and performed an ECG simultaneously. We used Bazett's formula to calculate QTc and defined QTc as prolonged when: >460 ms for women and >450 ms for men.Results: Seventy-seven percent (n = 17) of the subjects were men (mean age = 40 years) and 91% (n = 20) were diagnosed with schizophrenia. QTc's ranged from 369 to 437 ms. Patients receiving QTc prolonging drugs had significantly greater QTc interval compared to patients receiving non-prolonging drugs. Weak to moderate negative correlations were found between QTc interval and both defined daily dose (DDD) and antipsychotic plasma concentration. There was no statistical difference between the correlations for DDD and plasma concentration versus QTc interval.Conclusion: We did not find a stronger association between antipsychotic plasma concentration and QTc than between antipsychotic dose and QTc. We suggest close monitoring with regular electroencephalogram's until the development of a better marker for predicting the risk of cardiac arrhythmia.
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Affiliation(s)
- Lene Høimark
- Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark
| | - Lisbeth Uhrskov Sørensen
- Department of Forensic Psychiatry, Aarhus University Hospital Psychiatry, Aarhus, Denmark.,Department of Clinical Medicine, Health, Aarhus University, Aarhus, Denmark
| | - Ljubica Vukelic Andersen
- Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.,Department of Biomedicine, Health, Aarhus University, Aarhus, Denmark
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Hardy JR, Bundock D, Cross J, Gibbons K, Pinkerton R, Kindl K, Good P, Philip J. Prevalence of QTc Prolongation in Patients With Advanced Cancer Receiving Palliative Care-A Cause for Concern? J Pain Symptom Manage 2020; 59:856-863. [PMID: 31866486 DOI: 10.1016/j.jpainsymman.2019.12.356] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 12/10/2019] [Accepted: 12/11/2019] [Indexed: 11/18/2022]
Abstract
CONTEXT Medications commonly used for symptom control along with other known risk factors have the potential to prolong ventricular repolarization as measured by the QT interval (the time from the start of the Q wave to the end of the T wave) on a standard electrocardiogram (ECG). OBJECTIVES To document the prevalence of a prolonged QT interval corrected for heart rate (QTc) interval in the palliative/oncology setting, compare automatic ECG QTc measurements with manual readings and identify any correlation between QTc prolongation and the use of drugs or other risk factors. METHODS A convenience sample of consecutive patients with cancer, admitted under or known to the palliative/supportive care teams in two metropolitan hospitals, and willing to provide an ECG recording and basic demographic information including QTc risk factors were included. Both automated and manually calculated QTc intervals were recorded. Multivariable analysis was used to determine risk factors independently associated with prolonged QTc intervals. RESULTS Of the 389 participants, there was a significant difference in mean QTc between sites using automated but not manual calculations. Manual readings were therefore used with predetermined cutoffs of 0.44 seconds (males) and 0.46 seconds (females). Seventy-two (18.5%) of the participants had a prolonged QTc with six (1.5%) having a prolongation of >0.50 seconds. At-risk drugs were being taken by 218 participants (56.0% of total cohort). Factors shown to be associated with QTc prolongation included age, gender, performance status, and hypocalcemia. No specific medication was associated with increased risk. CONCLUSION Although almost 20% of patients receiving palliative care had prolongation of QTc, the possibility of serious consequences appeared to be low despite the frequent occurrence of risk factors.
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Affiliation(s)
- Janet R Hardy
- Department of Palliative and Supportive Care, Mater Misericordiae Ltd, South Brisbane, Queensland, Australia; Mater Research Institute - University of Queensland, South Brisbane, Queensland, Australia.
| | - Daniel Bundock
- Department of Palliative and Supportive Care, Mater Misericordiae Ltd, South Brisbane, Queensland, Australia
| | - Jessica Cross
- Department of Palliative and Supportive Care, Mater Misericordiae Ltd, South Brisbane, Queensland, Australia
| | - Kristen Gibbons
- Mater Research Institute - University of Queensland, South Brisbane, Queensland, Australia
| | - Ross Pinkerton
- Hummingbird House Hospice, Chermside, Queensland, Australia
| | - Korana Kindl
- St Vincent's Private Hospital Brisbane, Kangaroo Point, Queensland, Australia
| | - Phillip Good
- Department of Palliative and Supportive Care, Mater Misericordiae Ltd, South Brisbane, Queensland, Australia; Mater Research Institute - University of Queensland, South Brisbane, Queensland, Australia; St Vincent's Private Hospital Brisbane, Kangaroo Point, Queensland, Australia
| | - Jennifer Philip
- University of Melbourne and St. Vincent's Hospital, Melbourne, Victoria, Australia
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Hancox JC, Kalk NJ, Henderson G. Synthetic cannabinoids and potential cardiac arrhythmia risk: an important message for drug users. Ther Adv Drug Saf 2020; 11:2042098620913416. [PMID: 32269749 PMCID: PMC7093686 DOI: 10.1177/2042098620913416] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
- Jules C Hancox
- The School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol, BS8 1TD, UK
| | - Nicola J Kalk
- National Addictions Centre, Kings College London, UK
| | - Graeme Henderson
- The School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK
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Danielsson B, Collin J, Nyman A, Bergendal A, Borg N, State M, Bergfeldt L, Fastbom J. Drug use and torsades de pointes cardiac arrhythmias in Sweden: a nationwide register-based cohort study. BMJ Open 2020; 10:e034560. [PMID: 32169926 PMCID: PMC7069257 DOI: 10.1136/bmjopen-2019-034560] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE To study the occurrence of torsades de pointes (TdP) ventricular tachycardia in relation to use of drugs labelled with TdP risk, using two nationwide Swedish registers. DESIGN Prospective register-based cohort study. SETTING Entire Sweden. PARTICIPANTS Persons aged ≥18 years prescribed and dispensed any drug classified with TdP risk during 2006-2017, according to CredibleMeds. Persons with a registered TdP diagnosis during the study period, using drugs labelled with known (TdP 1), possible (TdP 2) or conditional (TdP 3) risk at the incident of TdP were examined. PRIMARY OUTCOME MEASURES Occurrence of TdP in relation to exposure rates for individual drugs with TdP risk. SECONDARY OUTCOME MEASURES Concurrent use of more than one TdP-labelled drug in a person with a TdP diagnosis. RESULTS During the study period, 410 TdP cases using drugs with TdP risk labels at the incident were registered; 205 women and 205 men, mean age 74.0 and 71.5 years, respectively. Antidepressants dominated (129/410, 30%), followed by antiarrhythmics (17%). Diuretics and gastric acid-secretion inhibitors, with TdP risk related to induction of hypokalaemia or hypomagnesaemia, were used in 56% and 32% of the 410 TdP cases, respectively. Among the most used antidepressants, citalopram with known TdP 1 risk was associated with both a higher absolute number and incidence of TdP per 100 000 users (two to four times), compared with mirtazapine with possible (TdP 2), and sertraline with conditional (TdP 3) risk. Multiple risk factors, including advanced age, cardiovascular disease and treatment with more than one TdP-classified drug, were frequently observed. CONCLUSIONS Antidepressants followed by antiarrhythmics dominated among TdP risk drugs used by adults with TdP diagnosis, the majority being ≥65 years. TdP risk class and concomitant medication should be considered when prescribing antidepressants to older patients.
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Affiliation(s)
- Bengt Danielsson
- Department of Analysis, Swedish National Board of Health and Welfare, Stockholm, Sweden
| | - Julius Collin
- Department of Analysis, Swedish National Board of Health and Welfare, Stockholm, Sweden
| | - Anastasia Nyman
- Department of Analysis, Swedish National Board of Health and Welfare, Stockholm, Sweden
| | - Annica Bergendal
- Department of Analysis, Swedish National Board of Health and Welfare, Stockholm, Sweden
| | - Natalia Borg
- Department of Analysis, Swedish National Board of Health and Welfare, Stockholm, Sweden
| | - Maria State
- Department of Analysis, Swedish National Board of Health and Welfare, Stockholm, Sweden
| | - Lennart Bergfeldt
- Department of Molecular and Clinical Medicine, University of Gothenburg, Goteborg, Sweden
| | - Johan Fastbom
- Department of Analysis, Swedish National Board of Health and Welfare, Stockholm, Sweden
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Wu C, Wang Y, Yang F, Shi W, Wang Z, He L, He Y, Shen J. Synthesis and Biological Evaluation of Five-Atom-Linker-Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile. ChemMedChem 2019; 14:2042-2051. [PMID: 31746558 DOI: 10.1002/cmdc.201900439] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 10/13/2019] [Indexed: 11/08/2022]
Abstract
Herein we describe a focused set of new arylpiperazine derivatives as potential broad-spectrum antipsychotics. The general structure contains a quinolinone-like moiety, an arylpiperazine moiety, and a five-atom linker. Among them, 7-(5-(4-(benzo[d]isothiazol-4-yl)piperazin-1-yl)pentyl)quinolin-2(1H)-one (S6) shows a promising preclinical profile. Compound S6, characterized by partial D2 R agonism, 5-HT1A R agonism, 5-HT2A R antagonism, and blockade of SERT activities, was found to decrease psychosis- and depressive-like symptoms in rodents. The polypharmacological profile of S6 could provide opportunities for the treatment of various other central nervous system disorders such as anxiety, depression, and psychoses associated with dementia. Furthermore, S6 demonstrated acceptable safety, toxicology, and pharmacokinetic profiles, and has been selected as a preclinical candidate for further evaluation in schizophrenia.
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Affiliation(s)
- Chunhui Wu
- Department of Pharmacology, China Pharmaceutical University, Nanjing, 210009, China.,Department of Druggability Evaluation, Topharman Shanghai Co. Ltd., Shanghai, 201203, China
| | - Yu Wang
- Department of Pharmacology, China Pharmaceutical University, Nanjing, 210009, China.,CAS Key Laboratory of Receptor Research Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China
| | - Feipu Yang
- CAS Key Laboratory of Receptor Research Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China
| | - Wenqiang Shi
- CAS Key Laboratory of Receptor Research Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China
| | - Zhen Wang
- CAS Key Laboratory of Receptor Research Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China
| | - Ling He
- Department of Pharmacology, China Pharmaceutical University, Nanjing, 210009, China
| | - Yang He
- CAS Key Laboratory of Receptor Research Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China
| | - Jingshan Shen
- CAS Key Laboratory of Receptor Research Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China
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Kim EY, Kim SH, Lee HJ, Lee NY, Kim HY, Park CHK, Ahn YM. A randomized, double-blind, 6-week prospective pilot study on the efficacy and safety of dose escalation in non-remitters in comparison to those of the standard dose of escitalopram for major depressive disorder. J Affect Disord 2019; 259:91-97. [PMID: 31445345 DOI: 10.1016/j.jad.2019.08.057] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 07/20/2019] [Accepted: 08/18/2019] [Indexed: 11/16/2022]
Abstract
BACKGROUND Escalating doses of selective serotonin reuptake inhibitors are often used to treat patients with a suboptimal response to the standard dose. This study assessed the efficacy and safety of dose escalation of escitalopram, up to 30 mg, in non-remitters with major depressive disorder (MDD) after treatment with the standard dose. METHOD We recruited 98 patients with MDD (aged 18-65 years). After 4 weeks of open-label treatment with 10-20 mg of escitalopram per day, non-remitters [Montgomery-Åsberg Depression Rating Scale (MADRS) score > 10] were randomized 1:1 for double-blind treatment with either escitalopram (30 mg per day) or escitalopram (20 mg per day) plus placebo for 6 weeks. The primary efficacy outcome was a change in the total MADRS score. RESULTS After 4 weeks of open-label treatment, 12 patients achieved remission, and 36 dropped out, leaving 50 non-remitters, of whom 44 (88%) completed the double-blind study. The primary outcome measure, the least-squares mean (standard error) change in the total MADRS score at week 6 was significantly different (p = 0.046) between the groups [-8.0 (1.2) in the placebo dose-escalation and -11.8 (1.2) in the escitalopram dose-escalation]. The dose escalation of escitalopram was well tolerated. However, the response and remission rates and quality of life showed no significant differences. LIMITATIONS Small sample size and short follow-up period CONCLUSION: This study suggests that dose escalation of escitalopram up to 30 mg per day may be beneficial for the treatment of depressive symptoms in non-remitters after standard (10-20 mg/day) treatment.
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Affiliation(s)
- Eun Young Kim
- Mental Health Center, Seoul National University Health Care Center, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea; Department of Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
| | - Se Hyun Kim
- Department of Psychiatry, Seoul National University Hospital, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea; Department of Psychiatry and Behavioral Science, Institute of Human Behavioral Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
| | - Hyun Jeong Lee
- Mental Health Clinic, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Republic of Korea; Cancer Survivorship Branch, National Cancer Control Institute, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Republic of Korea
| | - Nam Young Lee
- Department of Psychiatry, Dongguk University International Hospital, Dongguk University Medical School, 27 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Republic of Korea
| | - Hye Young Kim
- Department of Psychiatry, Inha University Hospital, 27 Inhang-ro, Jung-gu, Incheon 22332, Republic of Korea
| | - C Hyung Keun Park
- Department of Psychiatry and Behavioral Science, Institute of Human Behavioral Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea; Department of Psychiatry, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea
| | - Yong Min Ahn
- Department of Psychiatry, Seoul National University Hospital, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea; Department of Psychiatry and Behavioral Science, Institute of Human Behavioral Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea.
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Moriarty N, Alam M, Kalus A, O'Connor K. Current Understanding and Approach to Delusional Infestation. Am J Med 2019; 132:1401-1409. [PMID: 31295443 DOI: 10.1016/j.amjmed.2019.06.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 05/31/2019] [Accepted: 06/03/2019] [Indexed: 01/06/2023]
Abstract
Delusional infestation is a psychiatric condition defined by a fixed belief of infestation despite contrary evidence. Diagnosis includes exclusion of organic etiologies. Treatment with antipsychotics is effective and safe in the majority of patients. Patients are characteristically reluctant to pursue psychiatric evaluation and may resist discussing their disease in psychiatric terms. Strategies to strengthen the provider-patient therapeutic alliance facilitate communication around appropriate treatment. Without antipsychotic medications, patients can become heavy utilizers of care and practice self-destructive behaviors in attempts to clear their perceived infestation.
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Mizera L, Klingel K, Gawaz M, Greulich S. [Fatigue, breathlessness and chest pain in a 31-year-old man with schizoaffective disorder]. Internist (Berl) 2019; 60:1209-1214. [PMID: 31501912 DOI: 10.1007/s00108-019-00674-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Clozapine is an alternative antipsychotic medication used to control symptoms of schizophrenia and to reduce risks of suicidal behavior in patients who did not adequately respond to standard medication. Due to severe side effects including cardiomyopathy and myocarditis its clinical use is limited. CASE REPORT A 31-year-old man of east European descent presented to the emergency medical department with fatigue, shortness of breath and chest pain. Due to a schizoaffective disorder he was treated with clozapine and lithium. Echocardiography revealed severely impaired left ventricular systolic function. After exclusion of coronary artery disease by coronary angiography an endomyocardial biopsy was performed according to the guidelines. This confirmed the clinically suspected toxic cardiomyopathy. Therefore, antipsychotic treatment was immediately changed and state of the art heart failure medication was started resulting in a clear improvement of left ventricular function. CONCLUSION In patients treated with clozapine or lithium and clinical signs of heart failure, toxic cardiomyopathy should be considered.
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Affiliation(s)
- L Mizera
- Medizinische Klinik III - Kardiologie und Angiologie, Universitätsklinikum Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Deutschland
| | - K Klingel
- Institut für Pathologie und Neuropathologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - M Gawaz
- Medizinische Klinik III - Kardiologie und Angiologie, Universitätsklinikum Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Deutschland
| | - S Greulich
- Medizinische Klinik III - Kardiologie und Angiologie, Universitätsklinikum Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Deutschland.
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40
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Verdoux H, Pambrun E, Tournier M, Cortaredona S, Verger P. Multi-trajectories of antidepressant and antipsychotic use: a 11-year naturalistic study in a community-based sample. Acta Psychiatr Scand 2019; 139:536-547. [PMID: 30844084 DOI: 10.1111/acps.13020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/04/2019] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To explore the temporal dynamic of antidepressant and antipsychotic co-prescribing in real-life conditions. METHODS The study was performed using reimbursement data from the French Insurance Healthcare system in a cohort of 118 454 persons with at least one dispensing of antidepressants and/or antipsychotics over the period 2006-2016. Latent class analyses were used to identify homogeneous groups of persons following similar multi-trajectories of antidepressant and/or antipsychotic dispensing. Multivariate polynomial logistic regression models were used to explore the characteristics independently associated with distinct trajectories. RESULTS Five multi-trajectories of antidepressant and/or antipsychotic dispensing were identified: more than half of the sample (58%) had very low antidepressant and antipsychotic use; two groups had chronic (12%) or decreasing (11%) antidepressant use with very low antipsychotic use; two groups used both antidepressants and antipsychotics simultaneously either in an increasing (12%) or chronic (7%) way. Persons with chronic antidepressant-antipsychotic use presented with markers of poor social and mental health conditions. CONCLUSIONS Most persons using antipsychotics over the follow-up also used antidepressants over the same period. The benefit/risk ratio of these prescribing practices should be further explored as the long-term efficacy of antidepressant-antipsychotic polypharmacy is poorly documented, while this combination increases the risk of adverse effects.
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Affiliation(s)
- H Verdoux
- U1219, University of Bordeaux, Bordeaux, France.,INSERM, U1219, Bordeaux, France
| | - E Pambrun
- U1219, University of Bordeaux, Bordeaux, France.,INSERM, U1219, Bordeaux, France
| | - M Tournier
- U1219, University of Bordeaux, Bordeaux, France.,INSERM, U1219, Bordeaux, France
| | - S Cortaredona
- IRD, AP-HM, SSA, VITROME, IHU-Méditerranée Infection, Aix-Marseille University, Marseille, France
| | - P Verger
- IRD, AP-HM, SSA, VITROME, IHU-Méditerranée Infection, Aix-Marseille University, Marseille, France.,ORS PACA, Observatoire Régional de la Santé Provence-Alpes-Côte d'Azur, Marseille, France
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A retrospective comparison of inappropriate prescribing of psychotropics in three Norwegian nursing homes in 2000 and 2016 with prescribing quality indicators. BMC Med Inform Decis Mak 2019; 19:102. [PMID: 31142298 PMCID: PMC6542081 DOI: 10.1186/s12911-019-0821-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 05/14/2019] [Indexed: 11/28/2022] Open
Abstract
Background Inappropriate prescribing of psychotropics is a persistent and prevalent problem in nursing homes. The present study compared inappropriate prescribing of psychotropics in nursing homes 16 years apart with prescribing quality indicators. The purpose was to identify any change in inappropriate prescribing of relevance for medical informatics. Methods Three Norwegian nursing homes were audited in 2000 and 2016 with regard to prescribing quality. Psychotropics among 386 patients in 2000, and 416 patients in 2016, included combinations of antidepressants, antipsychotics, anxiolytics-hypnotics, and antiepileptics. Prescribing quality indicators included psychotropic polypharmacy (defined as concurrent use of three or more psychotropics) and potential inappropriate psychotropic substances or combinations. Furthermore, potential clinically relevant psychotropic interactions were classified as pharmacodynamic or pharmacokinetic using an interaction database. The first ranked (most important) interaction in each patient was selected with the following importance of categories in the database; recommended action > documentation > severity. Three levels (from low to high) within each category were used for ranking. Results From 2000 to 2016, psychotropic polypharmacy increased from 6.2 to 29.6%, potential inappropriate psychotropic substances was reduced from 17.9 to 11.3% and potential inappropriate psychotropic combinations increased from 7.8 to 27.9%. Changes in polypharmacy and combinations were predominantly associated with prescribing of anxiolytics-hypnotics. Sixty-three patients (16.3%) had psychotropic interactions in 2000 increasing to 146 patients (35.1%) in 2016. The increase in interactions was associated with prescribing of antidepressants. First ranked interactions, more than 60% of all interactions in both years, were increasingly pharmacodynamic, from 69.9 to 91.0%. Interactions in 2016 were associated with a lower level of recommended action and documentation, but not severity compared to 2000. The inappropriate prescribing of antipsychotics and antiepileptics was reduced in 2016 compared to 2000. Conclusions Using prescribing quality indicators we observed the importance of antidepressants and anxiolytics-hypnotics for inappropriate prescribing in 2016 while the role of antipsychotics and antiepileptics were reduced compared to 2000. A change to mainly pharmacodynamic interactions that lack good documentation was also observed. The present findings can be used for medical informatics-based approaches to address specific problems with prescribing, and prescribing quality indicators, in Norwegian nursing homes.
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Das B, Rawat VS, Ramasubbu SK, Kumar B. Frequency, characteristics and nature of risk factors associated with use of QT interval prolonging medications and related drug-drug interactions in a cohort of psychiatry patients. Therapie 2019; 74:599-609. [PMID: 31053339 DOI: 10.1016/j.therap.2019.03.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Revised: 01/22/2019] [Accepted: 03/11/2019] [Indexed: 01/08/2023]
Abstract
Quite a number of antipsychotic and antidepressant drugs are known to cause significant QT-prolongation. Psychiatric patients constitute a population at notable risk of drug-induced QT-prolongation. The aims were to explore frequency of use of QTc-interval prolonging agents and QT-prolonging drug-drug interactions, and prevalence of risk factors for QTc-interval prolongation in patients reporting to psychiatry out-patient department (OPD) in a tertiary care hospital in India. This prospective cross-sectional study was carried out in the psychiatry OPD at All India Institute of Medical Sciences (AIIMS), Rishikesh, Uttarakhand, India from October 1, 2017 to September 30, 2018 using the relevant prescriptions (i.e., the OPD case record forms and treatment sheets). For each patient, the entire medication list was analyzed for the possibility of interactions, with particular attention on the high-risk QT prolonging ones. Arizona Center for Education and Research on Therapeutics (AZCERT) QT drug lists were used to classify TdP risks of psychotropic and other medications. One thousand three hundred twenty-six (1326) patients attending the psychiatry OPD during the study period were scrutinized. Seven hundred fifty-one 751 patients (56.6%) were males whereas 575 (43.4%) were females in our study. Of the 1326 patients, 636 patients (47.9%) were identified as receiving interacting medications with the ability to induce torsades de pointe (TdP). Nine hundred seventeen (917) interacting medication pairs with torsadogenic risk were encountered. The most frequently interacting medications were from antipsychotic (794), antidepressant (519), antimicrobial (84), proton pump inhibitor (80), anticonvulsant (66), and anti-nausea (25) therapeutic categories. As per AZCERT classification (CredibleMeds TdP risk-stratification lists), 597 (36.8%), 443 (27.3%) and 432 (26.7%) of the interacting medications were associated with known, possible, and conditional risk of TdP, respectively. Concurrent prescriptions of QT-prolonging drugs is frequent in psychiatry OPD setting. Appropriate precautions should be instituted to obviate undesirable outcomes arising out of these interactions. This highlights the pressing need for clear protocols & strategies for implementation to motivate careproviders with clarity in the context of drug use guidelines for rational and safe prescribing in psychiatry.
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Affiliation(s)
- Biswadeep Das
- Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Rishikesh 249 203, Uttarakhand, India.
| | - Vikram Singh Rawat
- Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), Rishikesh 249 203, Uttarakhand, India
| | - Saravana Kumar Ramasubbu
- Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Rishikesh 249 203, Uttarakhand, India
| | - Barun Kumar
- Department of Cardiology, All India Institute of Medical Sciences (AIIMS), Rishikesh 249 203, Uttarakhand, India
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Association between citalopram, escitalopram and QTc prolongation in a real-world geriatric setting. J Affect Disord 2019; 250:341-345. [PMID: 30877856 DOI: 10.1016/j.jad.2019.02.060] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2018] [Revised: 01/17/2019] [Accepted: 02/25/2019] [Indexed: 11/23/2022]
Abstract
BACKGROUND Although the US Food and Drug Administration (FDA) recommended upper limits for citalopram dosing in older adults due to risk of corrected-QT (QTc) prolongation, which was adopted, and extended to escitalopram by Health Canada, the scientific basis is unclear. The objective of this study was to assess the relationship between citalopram/escitalopram dosages and QTc interval in a real-world geriatric setting. METHODS We reviewed electronic health records at a university-affiliated geriatric health care center, over a 7-year period, to identify patients prescribed citalopram and escitalopram, who had an ECG within 90 days of initiation or dosage change. Linear regression analyses were conducted to assess the relationship between antidepressant dosage and QTc interval. RESULTS 137 patients were identified (citalopram=97, escitalopram=40). No association was found between citalopram, escitalopram and QTc, in unadjusted or adjusted analyses. Among covariates, older age was significantly associated with QTc prolongation in the escitalopram group. LIMITATIONS Limitations to the current study include its retrospective design and the small sample size. CONCLUSIONS These data do not support the FDA or Health Canada's recommended maximum dosages of citalopram or escitalopram in the elderly. Therefore, for patients already on higher doses of these medications, the risk of QTc prolongation may not always outweigh the risk of dose lowering, such as relapse. Until larger prospective studies become available, the decision to comply or not with these federal agencies' recommendations should be weighed on an individual basis, taking into consideration all potential risk factors.
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Berling I, Hatten BW, Hoffman RS, Othong R, Roberts DM, Mustafa RA, Yates C, Cormier M, Gosselin S. Guidelines for reporting case studies and series on drug-induced QT interval prolongation and its complications following acute overdose. Clin Toxicol (Phila) 2019; 58:20-28. [DOI: 10.1080/15563650.2019.1605077] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Ingrid Berling
- Department of Emergency Medicine, Calvary Mater Newcastle, Newcastle, Australia
- School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia
| | - Benjamin W. Hatten
- Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Robert S. Hoffman
- Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, NYU School of Medicine, New York, NY, USA
| | - Rittirak Othong
- Department of Emergency Medicine, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
| | - Darren M. Roberts
- Department of Clinical Pharmacology and Toxicology, St Vincent’s Hospital and University of New South Wales, Sydney, Australia
| | - Reem A. Mustafa
- Department of Internal Medicine, The University of Kansas Healthcare System, Kansas City, KS, USA
| | - Christopher Yates
- Emergency Department/Clinical Toxicology Unit, Hospital Universitari Son Espases, Palma de Mallorca, Spain
| | - Monique Cormier
- Clinical Toxicology Recommendations Collaborative, American Academy of Clinical Toxicology, McLean, VA, USA
| | - Sophie Gosselin
- Department of Emergency Medicine, Hôpital Charles-Lemoyne, Greenfield Park, Canada
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Riordan PA, Briscoe J, Uritsky TJ, Jones CA, Webb JA. Top Ten Tips Palliative Care Clinicians Should Know About Psychopharmacology. J Palliat Med 2019; 22:572-579. [PMID: 30925078 DOI: 10.1089/jpm.2019.0106] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Palliative care (PC) providers often prescribe psychotropic medications to address psychological and physical suffering of patients with serious medical illness. Consideration must be given to the significant medical comorbidities of the patient when selecting a medication. This article seeks to provide guidance on how to safely and effectively select a psychotropic agent for depression, anxiety, and other distressing symptoms for patients with serious illness. To do so, we draw upon a team of physicians and a pharmacist with training in psychiatry and PC to highlight the "Top 10" tips for selecting a psychotropic medication to provide relief for patients with serious medical illness.
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Affiliation(s)
- Paul A Riordan
- 1 Section of Palliative Medicine, Duke University School of Medicine, Durham, North Carolina.,2 Department of Medicine, Duke University School of Medicine, Durham, North Carolina
| | - Joshua Briscoe
- 2 Department of Medicine, Duke University School of Medicine, Durham, North Carolina.,3 Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina
| | - Tanya J Uritsky
- 4 Clinical Pharmacy Specialist in Pain Medication Stewardship, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Christopher A Jones
- 5 Perelman School of Medicine and Palliative and Advanced Illness Research Center, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jason A Webb
- 1 Section of Palliative Medicine, Duke University School of Medicine, Durham, North Carolina.,2 Department of Medicine, Duke University School of Medicine, Durham, North Carolina.,3 Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina
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Baldaçara L, Diaz AP, Leite V, Pereira LA, Dos Santos RM, Gomes Júnior VDP, Calfat ELB, Ismael F, Périco CAM, Porto DM, Zacharias CEK, Cordeiro Q, da Silva AG, Tung TC. Brazilian guidelines for the management of psychomotor agitation. Part 2. Pharmacological approach. ACTA ACUST UNITED AC 2019; 41:324-335. [PMID: 30843960 PMCID: PMC6804299 DOI: 10.1590/1516-4446-2018-0177] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 09/18/2018] [Indexed: 01/07/2023]
Abstract
Objective: To present the essential guidelines for pharmacological management of patients with psychomotor agitation in Brazil. Methods: This is a systematic review of articles retrieved from the MEDLINE (PubMed), Cochrane Database of Systematic Reviews, and SciELO databases published from 1997 to 2017. Other relevant articles in the literature were also used to develop these guidelines. The search strategy used structured questions formulated using the PICO model, as recommended by the Guidelines Project of the Brazilian Medical Association. Recommendations were summarized according to their level of evidence, which was determined using the Oxford Centre for Evidence-based Medicine system and critical appraisal tools. Results: Of 5,362 articles retrieved, 1,731 abstracts were selected for further reading. The final sample included 74 articles that met all inclusion criteria. The evidence shows that pharmacologic treatment is indicated only after non-pharmacologic approaches have failed. The cause of the agitation, side effects of the medications, and contraindications must guide the medication choice. The oral route should be preferred for drug administration; IV administration must be avoided. All subjects must be monitored before and after medication administration. Conclusion: If non-pharmacological strategies fail, medications are needed to control agitation and violent behavior. Once medicated, the patient should be monitored until a tranquil state is possible without excessive sedation. Systematic review registry number: CRD42017054440.
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Affiliation(s)
- Leonardo Baldaçara
- Comissão de Emergências Psiquiátricas, Associação Brasileira de Psiquiatria, Rio de Janeiro, RJ, Brazil.,Universidade Federal do Tocantins (UFT), Palmas, TO, Brazil.,Secretaria de Estado de Saúde do Tocantins, Palmas, TO, Brazil
| | - Alexandre P Diaz
- Programa de Pós-Graduação em Ciências da Saúde, Universidade do Sul de Santa Catarina (UNISUL), Palhoça, SC, Brazil
| | - Verônica Leite
- Comissão de Emergências Psiquiátricas, Associação Brasileira de Psiquiatria, Rio de Janeiro, RJ, Brazil.,Secretaria de Estado de Saúde do Tocantins, Palmas, TO, Brazil.,Secretaria de Saúde do Município de Palmas, Palmas, TO, Brazil
| | - Lucas A Pereira
- Comissão de Emergências Psiquiátricas, Associação Brasileira de Psiquiatria, Rio de Janeiro, RJ, Brazil.,Universidade Salvador (UNIFACS), Salvador, BA, Brazil.,Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, BA, Brazil.,Faculdade de Tecnologia e Ciências (FTC), Salvador, BA, Brazil
| | - Roberto M Dos Santos
- Comissão de Emergências Psiquiátricas, Associação Brasileira de Psiquiatria, Rio de Janeiro, RJ, Brazil.,Hospital Universitário Lauro Wanderley, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, Brazil.,Pronto Atendimento em Saúde Mental, João Pessoa, PB, Brazil
| | - Vicente de P Gomes Júnior
- Comissão de Emergências Psiquiátricas, Associação Brasileira de Psiquiatria, Rio de Janeiro, RJ, Brazil.,Associação Psiquiátrica do Piauí (APPI), Teresina, PI, Brazil
| | - Elie L B Calfat
- Comissão de Emergências Psiquiátricas, Associação Brasileira de Psiquiatria, Rio de Janeiro, RJ, Brazil.,Faculdade de Medicina da Santa Casa de São Paulo (FCMSCSP), São Paulo, SP, Brazil.,Centro de Atenção Integrada à Saúde Mental, Franco da Rocha, SP, Brazil
| | - Flávia Ismael
- Comissão de Emergências Psiquiátricas, Associação Brasileira de Psiquiatria, Rio de Janeiro, RJ, Brazil.,Faculdade de Medicina do ABC, Santo André, SP, Brazil.,Coordenadoria de Saúde Mental, São Caetano do Sul, SP, Brazil.,Universidade de São Caetano do Sul, São Caetano do Sul, SP, Brazil
| | - Cintia A M Périco
- Comissão de Emergências Psiquiátricas, Associação Brasileira de Psiquiatria, Rio de Janeiro, RJ, Brazil.,Faculdade de Medicina do ABC, Santo André, SP, Brazil.,Coordenadoria de Saúde Mental, São Bernardo do Campo, SP, Brazil
| | - Deisy M Porto
- Comissão de Emergências Psiquiátricas, Associação Brasileira de Psiquiatria, Rio de Janeiro, RJ, Brazil.,Instituto de Psiquiatria de Santa Catarina, São José, SC, Brazil.,Coordenação Estadual de Saúde Mental, Florianópolis, SC, Brazil
| | - Carlos E K Zacharias
- Comissão de Emergências Psiquiátricas, Associação Brasileira de Psiquiatria, Rio de Janeiro, RJ, Brazil.,Secretaria de Estado da Saúde de São Paulo, São Paulo, SP, Brazil.,Secretaria de Saúde do Município de Sorocaba, São Paulo, SP, Brazil
| | - Quirino Cordeiro
- Comissão de Emergências Psiquiátricas, Associação Brasileira de Psiquiatria, Rio de Janeiro, RJ, Brazil.,Faculdade de Medicina da Santa Casa de São Paulo (FCMSCSP), São Paulo, SP, Brazil.,Coordenação-Geral de Saúde Mental, Álcool e Outras Drogas, Ministério da Saúde, Brazil
| | - Antônio Geraldo da Silva
- Asociación Psiquiátrica de América Latina (APAL)Asociación Psiquiátrica de América Latina (APAL).,ABP, Rio de Janeiro, RJ, Brazil.,Faculdade de Medicina, Universidade do Porto/Conselho Federal de Medicina (CFM), Porto, Portugal
| | - Teng C Tung
- Comissão de Emergências Psiquiátricas, Associação Brasileira de Psiquiatria, Rio de Janeiro, RJ, Brazil.,Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brazil
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Yun JY, Lee JS, Kang SH, Nam B, Lee SJ, Lee SH, Choi J, Kim CH, Chung YC. Korean Treatment Guideline on Pharmacotherapy of Co-existing Symptoms and Antipsychotics-related Side Effects in Patients with Schizophrenia. ACTA ACUST UNITED AC 2019. [DOI: 10.16946/kjsr.2019.22.2.21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Je-Yeon Yun
- Seoul National University Hospital, Seoul, Korea
- Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Korea
| | - Jung Suk Lee
- Department of Psychiatry, National Health Insurance Service Ilsan Hospital, Goyang, Korea
| | - Shi Hyun Kang
- Adult Psychiatry, Division of Medical Services, National Center for Mental Health, Seoul, Korea
| | - Beomwoo Nam
- Department of Psychiatry, School of Medicine, Konkuk University, Chungju, Korea
| | - Seung Jae Lee
- Department of Psychiatry, School of Medicine, Kyoungpook National University, Daegu, Korea
| | - Seung-Hwan Lee
- Department of Psychiatry, Inje University, Ilsan-Paik Hospital, Goyang, Korea
| | - Joonho Choi
- Department of Psychiatry, Hanyang University Guri Hospital, Guri, Korea
| | - Chan-Hyung Kim
- Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Young-Chul Chung
- Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea
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48
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Ansermot N, Bochatay M, Schläpfer J, Gholam M, Gonthier A, Conus P, Eap CB. Prevalence of ECG abnormalities and risk factors for QTc interval prolongation in hospitalized psychiatric patients. Ther Adv Psychopharmacol 2019; 9:2045125319891386. [PMID: 31853363 PMCID: PMC6909271 DOI: 10.1177/2045125319891386] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 10/21/2019] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Psychiatric patients are at risk of cardiovascular diseases, and many psychotropic drugs can prolong QTc interval. Requirements for electrocardiogram (ECG) monitoring have been set up in our psychiatric university hospital. The objective of this study was to determine the proportion of adult patients who had an ECG during their hospitalization, the prevalence of ECG abnormalities, the evolution of the QTc after admission, and the risk factors for QTc prolongation. METHODS Retrospective analysis of ECGs and clinical data of all patients with a complete hospitalization in 2015. Assessment of the influence of covariates on QTc using linear mixed-effects models. RESULTS At least one ECG (n = 600) was performed during 37.6% of the stays (n = 1198) and in 45.5% of the patients (n = 871). Among the patients with an ECG, 17.9% had significant ECG abnormalities, including 7.6% with a prolonged QTc. QTc measured at admission and during hospitalization did not change significantly (n = 46, 419.4 ± 29.7 ms, 417.2 ± 27.6 ms, p = 0.71). In the multivariate model (292 patients, 357 ECGs), the covariates significantly associated with the QTc were gender (+15.9 ms if female, p < 0.0001), age (+0.4 ms/year, p = 0.0001), triglyceride levels (+5.7 ms/mmol/l, p = 0.005), and drugs with known risk of torsades de pointes (+6.2 ms if ⩾1 drug, p = 0.028). CONCLUSIONS The prevalence of hospitalized psychiatric patients with an abnormal ECG indicates that ECGs should be performed systematically in this population. Prescription of psychotropic drugs should be done cautiously, particularly in patients with QTc prolongation risk factors.
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Affiliation(s)
- Nicolas Ansermot
- Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Hospital of Cery, 1008 Prilly, Switzerland
| | - Meredith Bochatay
- Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Prilly, Switzerland
| | - Jürg Schläpfer
- Department of Cardiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Mehdi Gholam
- Centre of Psychiatric Epidemiology and Psychopathology, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Prilly, Switzerland
| | - Ariane Gonthier
- General Internal Medicine Practice, Lausanne, Switzerland; University Institute of Medicine of the Family, University of Lausanne, Lausanne, Switzerland
| | - Philippe Conus
- Service of General Psychiatry, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Prilly, Switzerland
| | - Chin B Eap
- Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Prilly, Switzerland
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49
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Kahl KG. Direct and indirect effects of psychopharmacological treatment on the cardiovascular system. Horm Mol Biol Clin Investig 2018; 36:hmbci-2018-0054. [PMID: 30427780 DOI: 10.1515/hmbci-2018-0054] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 09/27/2018] [Indexed: 12/11/2022]
Abstract
Background Severe mental disorders, i.e. psychotic disorders, unipolar and bipolar disorders are associated with increased morbidity and mortality from cardiovascular and metabolic disorders. The underlying cause of this association is complex and comprises disorder specific alterations such as dysfunctions of immunological and hormonal systems, body-composition changes and health associated behaviors (smoking, sedentary lifestyle, alcohol intake and treatment compliance). Furthermore, some psychopharmacological drugs may exert unwanted side effects that impact the cardiovascular system. Methods This paper reviews studies concerning commonly used antidepressant and antipsychotics drugs with a particular focus on direct and indirect cardiovascular side effects. Results Newer antidepressant drugs have a favorable cardiovascular safety profile compared to tricyclic antidepressants. However, QTc prolongation, increased blood pressure and potentially higher risks of bleeding have been observed in some newer antidepressants. Some second generation (atypical) antipsychotics have raised concern because of indirect cardiovascular, metabolic side effects such as weight gain and disturbances in lipid and glucose metabolism. Conclusions Psychiatrists need to be aware of potential direct and indirect cardiovascular side effects and to include them in the risk/benefit assessment when choosing a specific individualized treatment.
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Affiliation(s)
- Kai G Kahl
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Center of Mental Health, Hannover Medical School (MHH), Carl-Neuberg-Str. 1, 30625 Hannover, Germany, Phone: + 49 511 5322495.,Working Group on Polypharmacy, AGNP, Munich, Germany
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50
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Shafiekhani M, Mirjalili M, Vazin A. Psychotropic drug therapy in patients in the intensive care unit - usage, adverse effects, and drug interactions: a review. Ther Clin Risk Manag 2018; 14:1799-1812. [PMID: 30319262 PMCID: PMC6168070 DOI: 10.2147/tcrm.s176079] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Managing psychological problems in patients admitted to intensive care unit (ICU) is a big challenge, requiring pharmacological interventions. On the other hand, these patients are more prone to side effects and drug interactions associated with psychotropic drugs use. Benzodiazepines (BZDs), antidepressants, and antipsychotics are commonly used in critically ill patients. Therefore, their therapeutic effects and adverse events are discussed in this study. Different studies have shown that non-BZD drugs are preferred to BZDs for agitation and pain management, but antipsychotic agents are not recommended. Also, it is better not to start antidepressants until the patient has fully recovered. However, further investigations are required for the use of psychotropic drugs in ICUs.
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Affiliation(s)
- Mojtaba Shafiekhani
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran,
| | - Mahtabalsadat Mirjalili
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran,
| | - Afsaneh Vazin
- Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran,
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