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Scala M, Chiera M, Bortolotti B, Rodriguez-Jimenez R, Menchetti M. Aggressive behaviour and diabetes: A clinical case of atypical metabolic improvement during clozapine treatment. JOURNAL OF INTELLECTUAL DISABILITIES : JOID 2024; 28:872-879. [PMID: 39041426 DOI: 10.1177/17446295241266897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/24/2024]
Abstract
Aggressive and violent behaviour is a challenging psychiatric emergency to manage, especially among vulnerable categories such as patients with Intellectual Developmental Disorder. Although there is some evidence that clozapine may be useful as an anti-violence compound, its use is limited by common metabolic complications. An adult patient presented with obesity, type II diabetes mellitus, compulsive food intake, severe Intellectual Developmental Disorder, and a treatment-resistant aggressive behaviour. Clozapine was administered resulting in reduced aggressive behaviour. Unexpectedly, a reduction in the food craving as well as a sustained improvement in both anthropometric parameters and glycemic control were observed during the clozapine treatment. Our case report, describes these findings for the first time, highlighting the need for more clinical research to investigate both the efficacy of clozapine in the Intellectual Developmental Disorder populations and its long-term effects with special regard to the metabolic outcomes in this type of patients.
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Affiliation(s)
- Mauro Scala
- Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum-University of Bologna, Italy
- Institute for Health Research Hospital Universitario 12 de Octubre, (imas12), Madrid, Spain
- Complutense University of Madrid (UCM), Madrid, Spain
| | - Martina Chiera
- Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum-University of Bologna, Italy
| | - Biancamaria Bortolotti
- Department of Mental Health and Pathological Dependencies, Local Health Authority of Bologna, Italy
| | - Roberto Rodriguez-Jimenez
- Institute for Health Research Hospital Universitario 12 de Octubre (imas12), Madrid, Spain
- Complutense University of Madrid (UCM), Madrid, Spain
- CIBERSAM-ISCIII (Biomedical Research Networking Centre in Mental Health), Madrid, Spain
| | - Marco Menchetti
- Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum-University of Bologna, Italy
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Hurley K, O’Brien S, Halleran C, Byrne D, Foley E, Cunningham J, Hoctor F, Sahm LJ. Metabolic Syndrome in Adults Receiving Clozapine; The Need for Pharmacist Support. PHARMACY 2023; 11:pharmacy11010023. [PMID: 36827661 PMCID: PMC9964454 DOI: 10.3390/pharmacy11010023] [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: 11/23/2022] [Revised: 01/20/2023] [Accepted: 01/21/2023] [Indexed: 01/27/2023] Open
Abstract
People who are diagnosed with treatment resistant schizophrenia (TRS) are likely to have clozapine as a therapeutic management option. There is a high prevalence of metabolic syndrome in patients receiving clozapine. To mitigate against this, monitoring of weight, waist circumference, lipid profile, glycated haemoglobin (HbA1c), fasting blood glucose (FBG) and blood pressure (BP) is recommended. The aims of this study were to examine the prevalence of metabolic syndrome and whether any variables were correlated with its development, and to highlight any opportunities for the pharmacist to offer support. This study was conducted in an urban hospital and its associated Clozapine Clinic in Cork, Ireland. A retrospective audit assessed the prevalence of metabolic syndrome using the International Diabetes Federation (IDF) criteria. Patients were eligible for inclusion if they were aged 18 years or more, registered with the Clozapine Clinic, and had the capacity to provide informed consent. All data were entered into Microsoft® Excel ® (Microsoft Corporation) and further statistical analysis was undertaken using R, t-tests, Fisher's Exact Test and Mann-Whitney U tests as appropriate, and p ≤ 0.05 was considered statistically significant. Of 145 patients (32% female; mean age (SD) 45.3 (±11.7) years; 86.2% living independently/in family home), nearly two thirds (n = 86, 59.3%) were diagnosed with metabolic syndrome. The mean age of participants with metabolic syndrome was 44.4 years (SD = 10.8), similar to the 46.6 years (SD = 12.8) for those without. Variables that were identified to be statistically significantly associated with metabolic syndrome included waist circumference, weight, triglycerides, high density lipoprotein-cholesterol (HDL-C), BP, FBG and HbA1c. The high incidence of metabolic syndrome in this patient population highlights the need for continued physical health monitoring of these patients to ameliorate the risk of developing metabolic syndrome.
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Affiliation(s)
- Kathleen Hurley
- Pharmacy Department, Mercy University Hospital, T12 WE28 Cork, Ireland
- Pharmaceutical Care Research Group, School of Pharmacy, University College Cork, T12 K8AF Cork, Ireland
- North Lee Mental Health Services (NLMHS), T12 WE28 Cork, Ireland
| | - Sinead O’Brien
- St Mary’s Health Campus, St Mary’s Campus, Gurranabraher, T23 TH9D Cork, Ireland
| | - Ciaran Halleran
- Pharmacy Department, Mercy University Hospital, T12 WE28 Cork, Ireland
| | - Derina Byrne
- Pharmacy Department, Mercy University Hospital, T12 WE28 Cork, Ireland
| | - Erin Foley
- North Lee Mental Health Services (NLMHS), T12 WE28 Cork, Ireland
| | | | - Fionnuala Hoctor
- Pharmaceutical Care Research Group, School of Pharmacy, University College Cork, T12 K8AF Cork, Ireland
| | - Laura J. Sahm
- Pharmacy Department, Mercy University Hospital, T12 WE28 Cork, Ireland
- Pharmaceutical Care Research Group, School of Pharmacy, University College Cork, T12 K8AF Cork, Ireland
- Correspondence:
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Patil V, Mishra K, John S, Reshamvala A. Clozapine-induced hypertension. ANNALS OF INDIAN PSYCHIATRY 2022. [DOI: 10.4103/aip.aip_99_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Nazir D, Wani ZA, Bukhari F, Dar SA, Kawoosa Y. Socio demographic, clinical, and side effect profile of patients on clozapine in Kashmir, North India. MIDDLE EAST CURRENT PSYCHIATRY 2021. [DOI: 10.1186/s43045-021-00163-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Clozapine is an atypical second-generation antipsychotic belonging to the family of dibenzodiazepines. There is lack of literature on clozapine from this part of the world. So, our aim was to study the socio demographic, clinical and side effect profile of patients on clozapine in Kashmir.
Results
The mean age of the study group was 32.6 ± 8.9 years with majority being males (78.4%), unmarried (78.4%), unemployed (77.2%), and belonging to nuclear families (77.2%). Almost half of them resided in urban localities (51.1%) and studied upto middle school (55.7%). Around three- fourth (75%) of the patients had diagnosis of treatment-resistant schizophrenia. The mean dose of clozapine was 338.92 ± 158.11 mgs. Sedation (76.1%), hypersalivation (69.5%), constipation (46.6%), and weight gain (34.1%) were most common side effects noted in patients. 4.5% cases developed seizures while on clozapine. 2.3% patients developed agranulocytosis while 4.5% patients developed neutropenia on clozapine. The neutropenia was more pronounced in patients of schizophrenia with suicidal tendencies with doses of more than 400 mg.
Conclusions
We have used clozapine in a wide range of indications. Our patients seem to tolerate and respond to higher doses of clozapine and the prevalence of blood dyscrasias in our study sample was much higher than the rest of India.
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Whiskey E, Barnard A, Oloyede E, Dzahini O, Taylor DM, Shergill SS. An evaluation of the variation and underuse of clozapine in the United Kingdom. Acta Psychiatr Scand 2021; 143:339-347. [PMID: 33501659 DOI: 10.1111/acps.13280] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 01/18/2021] [Accepted: 01/19/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND Clozapine is the only licensed treatment for treatment refractory schizophrenia. Despite this, it remains grossly underused relative to the prevalence of refractory schizophrenia. The extent of underuse and the degree of regional variation in prescribing in the United Kingdom is unknown. It is also unclear, how the UK compares with other European countries in rates of clozapine prescribing. METHODS We obtained data relating to all clozapine prescribing in the UK from the relevant clozapine registries. We examined regional variation in clozapine use across England, corrected for the known prevalence of severe mental illness (SMI). We also compared the UK rate of clozapine use per 100,000 population to that described in other European countries. FINDINGS There is substantial variation in clozapine prescribing across different regions of England and only about a third of potentially eligible patients were prescribed the drug in the UK. Clozapine prescribing rate in the UK was lower than in several European countries. INTERPRETATION There is clear regional inequity in access to the most effective treatment in refractory schizophrenia in England. Strategies to increase clozapine use, by overcoming both real and perceived barriers, are urgently necessary to reduce treatment inequity for patients with refractory schizophrenia.
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Affiliation(s)
- Eromona Whiskey
- Pharmacy Department, South London & Maudsley NHS Foundation Trust, London, UK.,Institute of Pharmaceutical Sciences, King's College, London, UK.,Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neurosciences, Kings College, London, UK
| | - Alex Barnard
- Clinical Research Network CRN, National Institute for Health Research NIHR, London, UK
| | - Ebenezer Oloyede
- Pharmacy Department, South London & Maudsley NHS Foundation Trust, London, UK.,Institute of Pharmaceutical Sciences, King's College, London, UK.,Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neurosciences, Kings College, London, UK
| | - Olubanke Dzahini
- Pharmacy Department, South London & Maudsley NHS Foundation Trust, London, UK.,Institute of Pharmaceutical Sciences, King's College, London, UK
| | - David M Taylor
- Pharmacy Department, South London & Maudsley NHS Foundation Trust, London, UK.,Institute of Pharmaceutical Sciences, King's College, London, UK
| | - Sukhwinder S Shergill
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neurosciences, Kings College, London, UK
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Carli M, Kolachalam S, Longoni B, Pintaudi A, Baldini M, Aringhieri S, Fasciani I, Annibale P, Maggio R, Scarselli M. Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences. Pharmaceuticals (Basel) 2021; 14:238. [PMID: 33800403 PMCID: PMC8001502 DOI: 10.3390/ph14030238] [Citation(s) in RCA: 122] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/02/2021] [Accepted: 03/03/2021] [Indexed: 12/15/2022] Open
Abstract
Atypical antipsychotics (AAPs) are commonly prescribed medications to treat schizophrenia, bipolar disorders and other psychotic disorders. However, they might cause metabolic syndrome (MetS) in terms of weight gain, dyslipidemia, type 2 diabetes (T2D), and high blood pressure, which are responsible for reduced life expectancy and poor adherence. Importantly, there is clear evidence that early metabolic disturbances can precede weight gain, even if the latter still remains the hallmark of AAPs use. In fact, AAPs interfere profoundly with glucose and lipid homeostasis acting mostly on hypothalamus, liver, pancreatic β-cells, adipose tissue, and skeletal muscle. Their actions on hypothalamic centers via dopamine, serotonin, acetylcholine, and histamine receptors affect neuropeptides and 5'AMP-activated protein kinase (AMPK) activity, thus producing a supraphysiological sympathetic outflow augmenting levels of glucagon and hepatic glucose production. In addition, altered insulin secretion, dyslipidemia, fat deposition in the liver and adipose tissues, and insulin resistance become aggravating factors for MetS. In clinical practice, among AAPs, olanzapine and clozapine are associated with the highest risk of MetS, whereas quetiapine, risperidone, asenapine and amisulpride cause moderate alterations. The new AAPs such as ziprasidone, lurasidone and the partial agonist aripiprazole seem more tolerable on the metabolic profile. However, these aspects must be considered together with the differences among AAPs in terms of their efficacy, where clozapine still remains the most effective. Intriguingly, there seems to be a correlation between AAP's higher clinical efficacy and increase risk of metabolic alterations. Finally, a multidisciplinary approach combining psychoeducation and therapeutic drug monitoring (TDM) is proposed as a first-line strategy to avoid the MetS. In addition, pharmacological treatments are discussed as well.
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Affiliation(s)
- Marco Carli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (S.K.); (B.L.); (A.P.); (M.B.); (S.A.)
| | - Shivakumar Kolachalam
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (S.K.); (B.L.); (A.P.); (M.B.); (S.A.)
| | - Biancamaria Longoni
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (S.K.); (B.L.); (A.P.); (M.B.); (S.A.)
| | - Anna Pintaudi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (S.K.); (B.L.); (A.P.); (M.B.); (S.A.)
| | - Marco Baldini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (S.K.); (B.L.); (A.P.); (M.B.); (S.A.)
| | - Stefano Aringhieri
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (S.K.); (B.L.); (A.P.); (M.B.); (S.A.)
| | - Irene Fasciani
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (I.F.); (R.M.)
| | - Paolo Annibale
- Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany;
| | - Roberto Maggio
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (I.F.); (R.M.)
| | - Marco Scarselli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (S.K.); (B.L.); (A.P.); (M.B.); (S.A.)
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Martini F, Spangaro M, Buonocore M, Bechi M, Cocchi F, Guglielmino C, Bianchi L, Sapienza J, Agostoni G, Mastromatteo A, Bosia M, Cavallaro R. Clozapine tolerability in Treatment Resistant Schizophrenia: exploring the role of sex. Psychiatry Res 2021; 297:113698. [PMID: 33440269 DOI: 10.1016/j.psychres.2020.113698] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 12/28/2020] [Indexed: 12/20/2022]
Abstract
Clozapine is the only evidence-based drug indicated for Treatment Resistant Schizophrenia but it is largely underprescribed, partially due to its life-threatening adverse effects (AEs). However, clozapine treatment is burdened by other common AEs as constipation, hypersalivation, postural hypotension, tachycardia and metabolic abnormalities. Few studies have investigated sex-related differences in clozapine's tolerability, reporting women to experience more frequently weight gain, hyperglycemia and constipation, while men hypertension and dyslipidemia. Based on these premises, we investigated clinical, psychopathological and metabolic sex-related differences among 147 treatment-resistant patients treated with clozapine, with a specific focus on non-life-threatening AEs. We observed significant higher prevalence of tachycardia in men, and of orthostatic hypotension and constipation in women. Concerning metabolic alterations, we observed significant lower levels of HDL-cholesterol and higher prevalence of hypertriglyceridemia among men, whereas females showed higher prevalence of abdominal obesity. Consistently with previous studies, our data confirm the presence of sex-related differences in clozapine tolerability, with a main effect of sex especially for tachycardia, postural hypotension and constipation. Although non-life-threatening, these common AEs significantly affect patients' quality of life, undermine compliance and cause treatment discontinuation. A better understanding of this topic could contribute to tailor therapeutic approaches, thus improving tolerability, compliance and clinical stability.
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Affiliation(s)
- Francesca Martini
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Marco Spangaro
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Mariachiara Buonocore
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Margherita Bechi
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Federica Cocchi
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carmelo Guglielmino
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Laura Bianchi
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | | | - Antonella Mastromatteo
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Marta Bosia
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Roberto Cavallaro
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
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8
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Li N, Cao T, Wu X, Tang M, Xiang D, Cai H. Progress in Genetic Polymorphisms Related to Lipid Disturbances Induced by Atypical Antipsychotic Drugs. Front Pharmacol 2020; 10:1669. [PMID: 32116676 PMCID: PMC7011106 DOI: 10.3389/fphar.2019.01669] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Accepted: 12/20/2019] [Indexed: 12/11/2022] Open
Abstract
Metabolic side effects such as weight gain and disturbed lipid metabolism are often observed in the treatment of atypical antipsychotic drugs (AAPDs), which contribute to an excessive prevalence of metabolic syndrome among schizophrenic patients. Great individual differences are observed but the underlying mechanisms are still uncertain. Research on pharmacogenomics indicates that gene polymorphisms involved in the pathways controlling food intake and lipid metabolism may play a significant role. In this review, relevant genes (HTR2C, DRD2, LEP, NPY, MC4R, BDNF, MC4R, CNR1, INSIG2, ADRA2A) and genetic polymorphisms related to metabolic side effects of AAPDs especially dyslipidemia were summarized. Apart from clinical studies, in vitro and in vivo evidence is also analyzed to support related theories. The association of central and peripheral mechanisms is emphasized, enabling the possibility of using peripheral gene expression to predict the central status. Novel methodological development of pharmacogenomics is in urgent need, so as to provide references for individualized medication and further to shed some light on the mechanisms underlying AAPD-induced lipid disturbances.
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Affiliation(s)
- Nana Li
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Ting Cao
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Xiangxin Wu
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Mimi Tang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.,Institute of Hospital Pharmacy, Xiangya Hospital, Central South University, Changsha, China
| | - Daxiong Xiang
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
| | - Hualin Cai
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China.,Institute of Clinical Pharmacy, Central South University, Changsha, China
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Grover S, Verma M, Chakrabarti S. Safety of Use of Clozapine in Patients With Schizophrenia With Comorbid Diabetes Mellitus. J Clin Psychopharmacol 2020; 40:276-282. [PMID: 32195772 DOI: 10.1097/jcp.0000000000001192] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
PURPOSE/BACKGROUND To evaluate the outcome of diabetes mellitus among patients of schizophrenia who had diabetes mellitus before starting clozapine. METHODS Clozapine data were screened to detect the patients who had diabetes mellitus before starting clozapine. Those who had diabetes mellitus before starting clozapine were taken up for the study. RESULTS Of the 468 records screened, 28 patients (5.6%) had diabetes mellitus before starting clozapine. Among the 28 patients, 15 (53.6%) were females, and 13 (46.4%) were male. In three-fourths (75%) of the patients, clozapine was started while these patients were admitted to the inpatient unit. Twenty-six patients had type 2 diabetes mellitus and 2 patients had type 1 diabetes mellitus at the time of starting clozapine. Most patients also had deranged blood glucose levels at the time of starting clozapine and required close monitoring of blood glucose levels and also starting/continuation of antidiabetic medications. None of the patients developed diabetic ketoacidosis during the initial part of the treatment. At the mean follow-up duration of 16 months, most patients were on regular follow-up for more than 1 year, and their blood glucose levels were maintained close to the reference range. Majority of these patients showed good response to clozapine. CONCLUSIONS The present study suggests that presence of diabetes mellitus should not stop the clinicians to use clozapine among patients with schizophrenia. However, close monitoring of blood glucose levels must be done.
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Affiliation(s)
- Sandeep Grover
- From the Department of Psychiatry, Postgraduate Institute of Medical Education & Research, Chandigarh, India
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10
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Huang TL, Lin CC, Tsai MC. Decreased serum S100A10 levels in patients with both schizophrenia and metabolic syndrome. TAIWANESE JOURNAL OF PSYCHIATRY 2020. [DOI: 10.4103/tpsy.tpsy_28_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Fernandez-Egea E, Walker R, Ziauddeen H, Cardinal RN, Bullmore ET. Birth weight, family history of diabetes and diabetes onset in schizophrenia. BMJ Open Diabetes Res Care 2020; 8:8/1/e001036. [PMID: 32049635 PMCID: PMC7039608 DOI: 10.1136/bmjdrc-2019-001036] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 01/02/2020] [Accepted: 01/07/2020] [Indexed: 01/09/2023] Open
Abstract
INTRODUCTION The prevalence of diabetes in schizophrenia is twice that in the general population, but there are few reliable predictors of which individuals will develop glucose dysregulation. OBJECTIVE To test if abnormal birth weight (either too low or too high) and parental diabetes, both variables that can be ascertained in the clinic, can predict diabetes onset in patients with schizophrenia. RESEARCH DESIGN AND METHODS Electronic records of a cohort of 190 clozapine-treated patients (37% treated for more than 20 years) and Cox regression survival analysis (with any type of glucose dysregulation as the event) to account for differences in length of treatment before the event and age at clozapine treatment initiation. RESULTS Age at clozapine initiation (Exp(B)=1.098; p<0.001), family history of diabetes (Exp(B)=2.299; p=0.049) and birth weight2 (Exp(B)=0.999; p=0.013) were significant predictors of glucose dysregulation onset, while gender was not (Exp(B)=0.1.350; p=0.517). Among individuals with 10 years of follow-up, 80% of those with both abnormal birth weight and a family history of diabetes developed diabetes compared with 56% with only abnormal birth weight, 40% with only a family history of diabetes and 20% in those with neither. CONCLUSIONS Since 48% of cases had at least one risk factor and 6% had both risk factors, there is a substantial proportion of patients for whom preventive strategies could be implemented.
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Affiliation(s)
- Emilio Fernandez-Egea
- Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
- Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
| | - Ryan Walker
- Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
| | - Hisham Ziauddeen
- Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
- Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
- Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK
| | - Rudolf N Cardinal
- Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
- Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
| | - Edward T Bullmore
- Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
- Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK
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Assessment of Long Term Metabolic Effects of Atypical Antipsychotics in Schizophrenia Patients. ROMANIAN JOURNAL OF DIABETES NUTRITION AND METABOLIC DISEASES 2019. [DOI: 10.2478/rjdnmd-2019-0028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Background and aims. Patients with schizophrenia have a shorter life expectancy than normal population partially due to the metabolic side effects of antipsychotic treatment. The aim of this study is to evaluate the long-term evolution of the metabolic syndrome in chronic schizophrenia patients on fixed second generation antipsychotics (SGA).
Material and method. The components of metabolic syndrome were evaluated repeatedly in a minimum 6 months and maximum 2 years follow-up period. The presence of metabolic syndrome (MetS) and metabolic risk scores (cMetS) according to National Cholesterol Education Program Adult Treatment Panel III were calculated and compared in time. In the prevalence, incidence and normalization logistic regression studies included all the known risk factors together with the follow-up period. Finally, all these rates were compared depending on the type of SGA.
Results. Only cMetS, waist circumference and diastolic blood pressure presented significant increase in the follow-up period which was in average 385.5 days. The prevalence of MetS at base-line was 39.4%, which increased to 48.5% after the follow-up period. The calculated incidence of 30% was associated with a 23.1% rate of normalization. Logistic regression studies revealed as independent risk factors the age and base-line cMetS/weight for incidence and for normalization. In the aripiprazole group the normalization rate exceeded the incidence rate (33.3% vs 20%).
Conclusions. The results emphasize the highly dynamic character of the metabolic syndrome even in chronic schizophrenia patients with fixed SGA regimen. The normalization of MetS is a possibility that should not ignored. The age and weight continue to remain independent risk factors, thus close monitoring in elderly and strict weight control plan are necessary. Aripiprazole showed better safety profile, but more extensive studies are required for definitive conclusions.
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Alberich S, Fernández-Sevillano J, González-Ortega I, Usall J, Sáenz M, González-Fraile E, González-Pinto A. A systematic review of sex-based differences in effectiveness and adverse effects of clozapine. Psychiatry Res 2019; 280:112506. [PMID: 31401291 DOI: 10.1016/j.psychres.2019.112506] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 08/01/2019] [Accepted: 08/02/2019] [Indexed: 12/17/2022]
Abstract
Clozapine is one of the most widely used antipsychotics for treating psychiatric illnesses such as schizophrenia and bipolar disorder. This drug, however, is associated with adverse effects such as weight gain, metabolic syndrome, and blood dyscrasias. The manifestations of mental illness may differ between men and women. Yet, there is little evidence on the influence of sex on treatment response or the occurrence of AEs. To fill this gap of knowledge, we carried out a systematic review of the literature on sex differences in the effectiveness and adverse effects of clozapine. Scant evidence has been published on differences in effectiveness of clozapine between men and women. Indeed, to the best of our knowledge, this issue has only been addressed in a published study. Regarding adverse effects, males have been reported to be more likely to develop metabolic abnormalities such as cholesterol or triglycerides, hypertension, and cardiovascular risk, while females are at a higher risk for gaining weight, developing diabetes, and needing laxatives. Nevertheless, given the scarcity of sex-based studies on this drug, further studies are needed to explore sex-based differences, as the results obtained may be crucial to clinical practice and help improve the quality of life of patients.
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Affiliation(s)
- Susana Alberich
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), BioAraba Research Institute, OSI Araba-University Hospital, Department of Psychiatry, Olaguibel Street 29, 01004, Vitoria, Spain; National Distance Education University Spain (UNED), Vitoria, Spain.
| | - Jessica Fernández-Sevillano
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), BioAraba Research Institute, OSI Araba-University Hospital, Department of Psychiatry, Olaguibel Street 29, 01004, Vitoria, Spain; University of the Basque Country (EHU/UPV), Spain
| | - Itxaso González-Ortega
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), BioAraba Research Institute, OSI Araba-University Hospital, Department of Psychiatry, Olaguibel Street 29, 01004, Vitoria, Spain; National Distance Education University Spain (UNED), Vitoria, Spain
| | - Judith Usall
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), University of Barcelona, Research Unit Parc Sanitari Sant Joan de Déu, Barcelona, Catalonia, Spain
| | - Marga Sáenz
- University of the Basque Country (EHU/UPV), Spain; Hospital Universitario Cruces, Biocruces, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Bilbao, España
| | | | - Ana González-Pinto
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), BioAraba Research Institute, OSI Araba-University Hospital, Department of Psychiatry, Olaguibel Street 29, 01004, Vitoria, Spain; University of the Basque Country (EHU/UPV), Spain
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14
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Cardio-metabolic risk and its management in a cohort of clozapine-treated outpatients. Schizophr Res 2018; 199:367-373. [PMID: 29486959 DOI: 10.1016/j.schres.2018.02.035] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 12/13/2017] [Accepted: 02/19/2018] [Indexed: 01/29/2023]
Abstract
OBJECTIVE To comprehensively assess cardio-metabolic risk factors and their management in a large sample of outpatients treated with clozapine. METHODS Observational cross-sectional study of all clozapine users attending specialized clozapine monitoring outpatient clinics in three public hospitals in Sydney, Australia were approached to participate over the one-year period 01/10/2015-30/09/2016. Cardio-metabolic risk factors including metabolic syndrome, risk for future development of diabetes, smoking, physical activity, nutrition, and prescribed medications were assessed at face-to-face interview and through medical record review. Among patients who had cardio-metabolic risk factors, the proportion receiving appropriate management was assessed. RESULTS Of 451 registered clozapine clinic attenders, 92.2% completed questionnaires and anthropometric measurements. 58.3% met criteria for metabolic syndrome. 79.6% were overweight or obese. 55.9% had blood pressure meeting metabolic syndrome criteria. 46.6% had elevated fasting blood glucose and 55.2% had elevated blood triglycerides. 43.6% were current smokers. Only 10% achieved recommended weekly physical activity levels. Unhealthy food categories were highly consumed. 32.1% were on additional antipsychotics. In the majority of individuals, cardio-metabolic risk factors were untreated or under-treated. CONCLUSIONS Clozapine use was associated with very high rates of cardiovascular and metabolic risk factors, which were frequently under-treated. Management of both physical and mental health should be prioritized. Polypharmacy should be rationalized. Future research should investigate the effectiveness of smoking cessation and lifestyle interventions in this high-risk population.
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Jeong SH, Lee NY, Kim SH, Chung IW, Youn T, Kang UG, Ahn YM, You HY, Kim YS. Long-Term Evolution of Metabolic Status in Patients with Schizophrenia Stably Maintained on Second-Generation Antipsychotics. Psychiatry Investig 2018; 15:628-637. [PMID: 29940717 PMCID: PMC6018140 DOI: 10.30773/pi.2018.01.18.1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 01/18/2018] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE Second-generation antipsychotics (SGAs) increase the risk of metabolic syndrome (MetS). Despite the risk of MetS, SGAs may have to be continued with change in some patients. The aim of this study was to trace the evolution of MetS in these patients. METHODS Patients with schizophrenia who had been maintained on a fixed SGA regimen for more than a year were followed-up without changing the regimen. Metabolic indicators were evaluated at baseline and at follow-up. Prevalence, incidence and spontaneous normalization rate of MetS were estimated. Risk factors that might have influenced the evolution were scrutinized. RESULTS A total of 151 subjects were included. During the mean observation period of 389.9±162.4 days, the prevalence of MetS was increased from 35.1 to 45.0%. The incidence rate was 29.6%, while the normalization rate was 26.4%, risk factors affecting incidence were age (OR=1.09, 95% CI: 1.03-1.17), baseline continuous values of metabolic syndrome risk scores (cMetS, OR=1.77, 95% CI:1.29-2.55) and baseline body weight (OR=1.06, 95% CI: 1.01-1.13). Normalization was influenced by age (OR=0.74, 95% CI: 0.57-0.89) and baseline body weight (OR=0.85, 95% CI: 0.72-0.95). CONCLUSION The prevalence of MetS steadily increased with the continuous use of SGAs. However, individual difference was extensive and about a quarter of the patients were able to recover naturally without specific measurements.
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Affiliation(s)
- Seong Hoon Jeong
- Department of Psychiatry, Eulji University School of Medicine, Eulji University Hospital, Daejeon, Republic of Korea
| | - Nam Young Lee
- Department of Neuropsychiatry and Institute of Clinical Psychopharmacology, Dongguk University International Hospital, Goyang, Republic of Korea
| | - Se Hyun Kim
- Department of Neuropsychiatry and Institute of Clinical Psychopharmacology, Dongguk University International Hospital, Goyang, Republic of Korea
| | - In Won Chung
- Department of Neuropsychiatry and Institute of Clinical Psychopharmacology, Dongguk University International Hospital, Goyang, Republic of Korea
| | - Tak Youn
- Department of Neuropsychiatry and Institute of Clinical Psychopharmacology, Dongguk University International Hospital, Goyang, Republic of Korea
| | - Ung Gu Kang
- Institute of Human Behavioral Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea.,Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yong Min Ahn
- Institute of Human Behavioral Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea.,Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Han Young You
- College of Nursing Science, Ewha Woman's University, Seoul, Republic of Korea
| | - Yong Sik Kim
- Department of Neuropsychiatry and Institute of Clinical Psychopharmacology, Dongguk University International Hospital, Goyang, Republic of Korea
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Wang HY, Huang CLC, Feng IJ, Tsuang HC. Second-generation antipsychotic medications and risk of chronic kidney disease in schizophrenia: population-based nested case-control study. BMJ Open 2018; 8:e019868. [PMID: 29794090 PMCID: PMC5988075 DOI: 10.1136/bmjopen-2017-019868] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVES The study aims to compare the risk of chronic kidney diseases (CKDs) between patients with schizophrenia using first and second-generation antipsychotics. SETTING Datasets of 2000-2013 National Health Insurance in Taiwan were used. PARTICIPANTS The National Health Insurance reimbursement claims data have been transferred to and managed by the National Health Research Institute in Taiwan since 1996. We used the Psychiatric Inpatient Medical Claims database, a subset of the National Health Insurance Research Database, comprising a cohort of patients hospitalised for psychiatric disorders between 2000 and 2013 (n=2 67 807). The database included patients with at least one psychiatric inpatient record and one discharge diagnosis of mental disorders coded by the International Classification of Diseases, Ninth Revision (ICD-9) codes 290-319. The age of patients at first admission was restricted to 18-65 years. PRIMARY OUTCOME CKD (ICD-9 code 582, 583, 585, 586, 588) requiring hospitalisation or three outpatient visits. The diagnosis of CKD follows the criteria of 'Kidney Disease: Improving Global Outcomes' in Taiwan. CKD is defined as a kidney damage as albumin-to-creatinine ratio >30 mg/g in two of three spot urine specimens or glomerular filtration rate <60 mL/min/1.73 m2 for 3 months or more. RESULTS We found that the risks for CKD were higher for those who used second-generation antipsychotics (SGAs) longer cumulatively than those who did not. Using non-users, patients did not have any SGA records, as reference group, the risks for CKD comparing those using SGAs for 90 to 180 days with non-users and those using SGAs for more than 1000 days were 1.42 (1.06-1.91) and 1.30 (1.13-1.51), respectively. CONCLUSIONS The current study suggests the relationship between using SGAs and risk of CKD.
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Affiliation(s)
- Hsien-Yi Wang
- Division of Nephrology, Chi Mei Medical Center, Yung Kang, Taiwan
- Department of Sport Management, College of Leisure and Recreation Management, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Charles Lung-Cheng Huang
- Division of Psychiatry, Chi Mei Medical Center, Yung Kang, Taiwan
- Department of Social Work, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan
| | - I Jung Feng
- Department of Medical Research, Chi Mei Medical Center, Yung Kang, Taiwan
| | - Hui-Chun Tsuang
- Center of General Education, Chang Jung Christian University, Tainan, Taiwan
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Guma E, Rocchetti J, Devenyi GA, Tanti A, Mathieu A, Lerch JP, Elgbeili G, Courcot B, Mechawar N, Chakravarty MM, Giros B. Regional brain volume changes following chronic antipsychotic administration are mediated by the dopamine D2 receptor. Neuroimage 2018; 176:226-238. [PMID: 29704613 DOI: 10.1016/j.neuroimage.2018.04.054] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Revised: 04/17/2018] [Accepted: 04/23/2018] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Neuroanatomical alterations are well established in patients suffering from schizophrenia, however the extent to which these changes are attributable to illness, antipsychotic drugs (APDs), or their interaction is unclear. APDs have been extremely effective for treatment of positive symptoms in major psychotic disorders. Their therapeutic effects are mediated, in part, through blockade of D2-like dopamine (DA) receptors, i.e. the D2, D3 and D4 dopamine receptors. Furthermore, the dependency of neuroanatomical change on DA system function and D2-like receptors has yet to be explored. METHODS We undertook a preclinical longitudinal study to examine the effects of typical (haloperidol (HAL)) and atypical (clozapine (CLZ)) APDs in wild type (WT) and dopamine D2 knockout (D2KO) mice over 9-weeks using structural magnetic resonance imaging (MRI). RESULTS Chronic typical APD administration in WT mice was associated with reductions in total brain (p = 0.009) and prelimbic area (PL) (p = 0.02) volumes following 9-weeks, and an increase in striatal volume (p = 0.04) after six weeks. These APD-induced changes were not present in D2KOs, where, at baseline, we observed significantly smaller overall brain volume (p < 0.01), thinner cortices (q < 0.05), and enlarged striata (q < 0.05). Stereological assessment revealed increased glial density in PL area of HAL treated wild types. Interestingly, in WT and D2KO mice, chronic CLZ administration caused more limited changes in brain structure. CONCLUSIONS Our results present evidence for the role of D2 DA receptors in structural alterations induced by the administration of the typical APD HAL and that chronic administration of CLZ has a limited influence on brain structure.
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Affiliation(s)
- Elisa Guma
- Department of Psychiatry & Integrated Program in Neuroscience, McGill University, 845 Sherbrooke St W, Montreal, QC, H3A 0G4 Canada; Cerebral Imaging Center, Douglas Mental Health University Institute, Verdun, Quebec, H4H 1R3, Canada
| | - Jill Rocchetti
- Department of Psychiatry & Integrated Program in Neuroscience, McGill University, 845 Sherbrooke St W, Montreal, QC, H3A 0G4 Canada
| | - Gabriel A Devenyi
- Cerebral Imaging Center, Douglas Mental Health University Institute, Verdun, Quebec, H4H 1R3, Canada
| | - Arnaud Tanti
- McGill Group for Suicide Studies, Department of Psychiatry, McGill University, Douglas Mental Health University Institute, Montreal, QC, Canada
| | - Axel Mathieu
- Cerebral Imaging Center, Douglas Mental Health University Institute, Verdun, Quebec, H4H 1R3, Canada
| | - Jason P Lerch
- Mouse Imaging Center - Hospital for Sick Children, Department of Medical Biophysics -University of Toronto, Toronto, Ontario, M5T 3H7, Canada
| | - Guillaume Elgbeili
- Department of Psychiatry & Integrated Program in Neuroscience, McGill University, 845 Sherbrooke St W, Montreal, QC, H3A 0G4 Canada
| | - Blandine Courcot
- Cerebral Imaging Center, Douglas Mental Health University Institute, Verdun, Quebec, H4H 1R3, Canada
| | - Naguib Mechawar
- McGill Group for Suicide Studies, Department of Psychiatry, McGill University, Douglas Mental Health University Institute, Montreal, QC, Canada
| | - M Mallar Chakravarty
- Department of Psychiatry & Integrated Program in Neuroscience, McGill University, 845 Sherbrooke St W, Montreal, QC, H3A 0G4 Canada; Cerebral Imaging Center, Douglas Mental Health University Institute, Verdun, Quebec, H4H 1R3, Canada; Department of Biological and Biomedical Engineering, McGill University, 845 Sherbrooke St W, Montreal, QC, H3A 0G4, Canada
| | - Bruno Giros
- Department of Psychiatry & Integrated Program in Neuroscience, McGill University, 845 Sherbrooke St W, Montreal, QC, H3A 0G4 Canada; Sorbonne University, Neuroscience Paris Seine, CNRS UMR 8246, INSERM U 1130, UPMC Univ Paris 06, UM119, 75005, Paris, France.
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Lin YC, Lai CL, Chan HY. The association between rehabilitation programs and metabolic syndrome in chronic inpatients with schizophrenia. Psychiatry Res 2018; 260:227-232. [PMID: 29216485 DOI: 10.1016/j.psychres.2017.11.081] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2017] [Revised: 10/04/2017] [Accepted: 11/26/2017] [Indexed: 11/25/2022]
Abstract
The correlation between different rehabilitation programs and the prevalence of metabolic syndrome in people with schizophrenia is unclear. We tested the association in chronic inpatients with schizophrenia of a psychiatric hospital in Taiwan. Patients with schizophrenia and age from 20 to 65 years old were included. The criteria of metabolic syndrome were according to the adapted Adult Treatment Protocol for Asians. According to different types of rehabilitations, patients were divided into work group, occupational therapy group and daily activities group. A total of 359 chronic inpatients with schizophrenia were recruited. Participants had a mean age of 45.9 years and the prevalence of metabolic syndrome was 37.3%. There was a significantly higher prevalence of metabolic syndrome in the work group than in the daily activity group (adjusted odds ratio (aOR) = 1.91, 95% CI = 1.019-3.564, p < 0.05) after adjusted related confounders. Other factors associated with higher prevalence of metabolic syndrome included old age, female gender, low psychotic symptoms severity and clozapine user. This study identified a high prevalence of metabolic syndrome in chronic inpatients with schizophrenia especially in patients with good occupational function. Further investigation of the relationship between the occupational function and metabolic syndrome is necessary for chronic inpatients with schizophrenia.
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Affiliation(s)
- Yi-Chun Lin
- Department of General Psychiatry, Taoyuan Psychiatric Center, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Chien-Liang Lai
- Department of General Psychiatry, Taoyuan Psychiatric Center, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Hung-Yu Chan
- Department of General Psychiatry, Taoyuan Psychiatric Center, Ministry of Health and Welfare, Taoyuan, Taiwan; Department of Psychiatry, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
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19
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Norman SM, Sullivan KM, Liu F, DiPaula BA, Jose PA, Kitchen CA, Feldman SM, Kelly DL. Blood Pressure and Heart Rate Changes During Clozapine Treatment. Psychiatr Q 2017; 88:545-552. [PMID: 27678498 PMCID: PMC5471124 DOI: 10.1007/s11126-016-9468-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
People with schizophrenia are 3-4 times more likely to die from cardiovascular disease than the general population. Clozapine (CLZ) is the gold standard of treatment for refractory schizophrenia. It has been associated with tachycardia and recent evidence shows individuals prescribed CLZ may develop blood pressure (BP) elevation and hypertension. The purpose of this study was to examine the effects of CLZ on BP and heart rate (HR). This was a retrospective chart review of patients 18-75 years old with a DSM IV diagnosis of Schizophrenia or Schizoaffective disorder. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measured 12 weeks before and 24 weeks during CLZ treatment. Eighteen patient records were included in this study. The mean stabilized CLZ dose was 441.7 ± 171.8 mg/day. DBP (t = 1.02, df = 79.5, = 2.00, 0.049) and HR (t = 1.32, df = 355 = -4.61, < 0.0001) were significantly higher after CLZ initiation. A trend was noted for increase in SBP (p = 0.071). 22 % of patients met criteria for hypertension before CLZ and 67 % during CLZ treatment (Chi Square = 6.25, df = 1, p = 0.0124). No significant changes in weight or renal function occured during CLZ treatment. No patients had evidence of cardiomyopathy. The data suggest CLZ may be associated with a rise in BP and HR. The results of this study support previous literature that found an increase in SBP/DBP regardless of CLZ dose, occurring early in treatment. Due to high risk of cardiovascular morbidity and mortality, more work is needed to determine risk factors and understand the mechanism of action that may cause this side effect.
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Affiliation(s)
- Sarah M Norman
- University of Maryland School of Pharmacy, 20 N. Pine St, Baltimore, MD, 21201, USA
| | - Kelli M Sullivan
- Marsico Lung Institute/Cystic Fibrosis Center, University of North Carolina at Chapel Hill, 7222 Marsico Hall CB #7248, Chapel Hill, NC, 27599, USA
| | - Fang Liu
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, 55 Wade Avenue, Catonsville, MD, 21228, USA
| | - Bethany A DiPaula
- University of Maryland School of Pharmacy, 20 N. Pine St, Baltimore, MD, 21201, USA
| | - Pedro A Jose
- Division of Renal Diseases & Hypertension, The George Washington University School of Medicine and Health Sciences, 2300 I St NW #601, Washington, DC, 20052, USA
| | - Christopher A Kitchen
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, 55 Wade Avenue, Catonsville, MD, 21228, USA
| | - Stephanie M Feldman
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, 55 Wade Avenue, Catonsville, MD, 21228, USA
| | - Deanna L Kelly
- Maryland Psychiatric Research Center, University of Maryland School of Medicine, 55 Wade Avenue, Catonsville, MD, 21228, USA.
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20
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Lin CC, Hung YY, Tsai MC, Huang TL. Increased serum brain-derived neurotrophic factor in male schizophrenic patients with metabolic syndrome. Medicine (Baltimore) 2017; 96:e7089. [PMID: 28562580 PMCID: PMC5459745 DOI: 10.1097/md.0000000000007089] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Increased prevalence of metabolic syndrome was found in patients with schizophrenia. Brain-derived neurotrophic factor (BDNF) was involved in energy metabolism and the pathophysiology of schizophrenia, but differently in males and females. We aimed to investigate the serum BDNF levels in patients with schizophrenia with and without metabolic syndrome.Patients with schizophrenia were recruited. Their demographic data were collected. Metabolic profiles and serum BDNF levels were measured. Clinical symptoms were evaluated with Positive and Negative Syndrome Scale. Metabolic syndrome was determined with the criteria provided by Ministry of Health and Welfare of Taiwan. Framingham Risk Score (FRS) for estimate of 10-year risk for coronary heart disease was provided by National Institutes of Health.Of the 81 participants, 40.7% had metabolic syndrome. Those with metabolic syndrome had higher FRS. Using analysis of covariance adjusted for age and body mass index, male patients with schizophrenia with metabolic syndrome had higher serum BDNF levels than those without (4.6 ± 4.7 vs 3.3 ± 3.8 ng/mL, P = .022). No statistical difference was found between female patients with and without metabolic syndrome.Significant differences of serum BDNF levels were found between male patients with schizophrenia with and without metabolic syndrome, but not in females. This finding suggested the gender difference behind the mechanism of BDNF in metabolic syndrome in schizophrenia.
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Clozapine usage increases the incidence of pneumonia compared with risperidone and the general population: a retrospective comparison of clozapine, risperidone, and the general population in a single hospital over 25 months. Int Clin Psychopharmacol 2017; 32:155-160. [PMID: 28059928 DOI: 10.1097/yic.0000000000000162] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The aim of this study was to determine whether the incidence of pneumonia in patients taking clozapine was more frequent compared with those taking risperidone or no atypical antipsychotics at all before admission to a tertiary care medical center. This was a retrospective, case-matched study of 465 general medicine patients over a 25 month period from 1 July 2010 to 31 July 2012. Detailed electronic medical records were analyzed to explore the association between the use of two atypical antipsychotics and incidence of pneumonia. Of the 155 patients in the clozapine group, 54 (34.8%) had documented pneumonia compared with 22 (14.2%) in the risperidone group and 18 (11.6%) in the general population group. Clozapine, when compared with the untreated general population, was associated with an increased risk of pneumonia (odds ratio=4.07; 95% confidence interval=2.25-7.36). There was, however, no significant increase in the risk of pneumonia associated with the use of risperidone (odds ratio=1.26; 95% confidence interval=0.65-2.45). Clozapine use is associated with increased risk of pneumonia that may be related to immunologic factors or side effects of sedation and drooling that make aspiration more likely, although causative mechanisms require further investigation. These findings suggest that providers should use added caution in choosing candidates for clozapine therapy.
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A Pilot Study of Randomized, Head-to-Head of Metformin Versus Topiramate in Obese People With Schizophrenia. Clin Neuropharmacol 2016; 39:306-310. [DOI: 10.1097/wnf.0000000000000188] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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Zimbron J, Khandaker GM, Toschi C, Jones PB, Fernandez-Egea E. A systematic review and meta-analysis of randomised controlled trials of treatments for clozapine-induced obesity and metabolic syndrome. Eur Neuropsychopharmacol 2016; 26:1353-1365. [PMID: 27496573 DOI: 10.1016/j.euroneuro.2016.07.010] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 07/04/2016] [Accepted: 07/19/2016] [Indexed: 12/20/2022]
Abstract
Metabolic complications are commonly found in people treated with clozapine. Reviews on the management of this problem have generally drawn conclusions by grouping different types of studies involving patients treated with various different antipsychotics. We carried out a systematic review and meta-analysis of pharmacological and non-pharmacological treatments for clozapine-induced obesity or metabolic syndrome. Two researchers independently searched PubMed and Embase for randomised controlled trials (RCTs) of treatments for clozapine-induced obesity or metabolic syndrome. All other types of studies were excluded. We only included RCTs where more than 50% of participants were taking clozapine. We identified 15 RCTs. Effective pharmacological treatments for clozapine-induced obesity and metabolic syndrome include metformin, aripiprazole, and Orlistat (in men only). Meta-analysis of three studies showed a robust effect of metformin in reducing body mass index and waist circumference but no effects on blood glucose, triglyceride levels, or HDL levels. In addition, there is limited evidence for combined calorie restriction and exercise as a non-pharmacological alternative for the treatment of clozapine-induced obesity, but only in an in-patient setting. Rosiglitazone, topiramate, sibutramine, phenylpropanolamine, modafinil, and atomoxetine have not shown to be beneficial, despite reports of efficacy in other populations treated with different antipsychotics. We conclude that randomised-controlled trial data support the use of metformin, aripiprazole, and Orlistat (in men only) for treating clozapine-induced obesity. Calorie restriction in combination with an exercise programme may be effective as a non-pharmacological alternative. Findings from trials in different populations should not be extrapolated to people being treated with clozapine.
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Affiliation(s)
- Jorge Zimbron
- Department of Psychiatry, University of Cambridge, UK; Elizabeth House, Fulbourn Hospital, Fulbourn, Cambridge, CB21 5EF, UK.
| | - Golam M Khandaker
- Department of Psychiatry, University of Cambridge, UK; Elizabeth House, Fulbourn Hospital, Fulbourn, Cambridge, CB21 5EF, UK
| | - Chiara Toschi
- Department of Neuropsychiatry, University College London, Gower Street, London, WC1E 6BT, UK
| | - Peter B Jones
- Department of Psychiatry, University of Cambridge, UK
| | - Emilio Fernandez-Egea
- Department of Psychiatry, University of Cambridge, UK; Elizabeth House, Fulbourn Hospital, Fulbourn, Cambridge, CB21 5EF, UK; Behavioural and Clinical Neuroscience Institute (BCNI), University of Cambridge, UK
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Young SL, Taylor M, Lawrie SM. "First do no harm." A systematic review of the prevalence and management of antipsychotic adverse effects. J Psychopharmacol 2015; 29:353-62. [PMID: 25516373 DOI: 10.1177/0269881114562090] [Citation(s) in RCA: 130] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
AIMS We aim to identify the prevalence and management strategies of nine clinically important categories of antipsychotic adverse effects, namely: extrapyramidal symptoms; sedation; weight gain; type II diabetes; hyperprolactinaemia; metabolic syndrome, dyslipidaemia; sexual dysfunction; and cardiovascular effects. BACKGROUND Antipsychotic drugs are widely prescribed for schizophrenia and other mental disorders. The adverse effects of antipsychotics are common, with a potential negative impact on adherence and engagement. Despite this, the scientific study of the prevalence or management of adverse antipsychotic effects is a neglected area. METHOD A systematic review was undertaken using pre-defined search criteria and three databases, with hand searching of citations and references. Inclusion was agreed on by two independent researchers after review of abstracts or full text. Quality analysis of included studies was conducted using pre-agreed criteria. RESULTS In total, 53 studies met inclusion criteria, revealing the following: (1) antipsychotic polypharmacy was associated with increased frequency of adverse effects, and (2) a longer duration of treatment is associated with greater severity (e.g. higher BMI); (3) clozapine was more strongly associated with metabolic disturbance than other antipsychotics in three studies and olanzapine was associated with the most weight gain in three studies; (4) hyperprolactinaemia was more common in women than men, but 50% men noted sexual dysfunction versus 25-50% in women; (5) despite clinical guideline recommendations there is a low rate of baseline testing for lipids and glucose; and (6) seven studies described adverse effect management strategies, but only two examined their efficacy - one found a significant reduction in weight with non-pharmacological group therapy and the other found a significant reduction in dyslipidaemia with statins. CONCLUSIONS Antipsychotic adverse effects are diverse and frequently experienced, but are not often systematically assessed. There is a need for further scientific study concerning the management of these side effects.
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Abitbol R, Rej S, Segal M, Looper KJ. Diabetes mellitus onset in geriatric patients: does long-term atypical antipsychotic exposure increase risk? Psychogeriatrics 2015; 15:43-50. [PMID: 25369990 DOI: 10.1111/psyg.12081] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 08/10/2014] [Accepted: 09/04/2014] [Indexed: 11/28/2022]
Abstract
BACKGROUND Diabetes mellitus (DM) in common in adults using psychotropic medications. However, it remains largely unknown whether there is an additional risk of diabetes mellitus (DM) in elderly psychiatric outpatients, particularly those with long-term exposure to atypical antipsychotics (AP). METHODS In this retrospective longitudinal study, 61 atypical AP-exposed and 64 atypical AP-unexposed geriatric psychiatric patients were compared to a group of 200 psychotropic-naïve controls. Our main composite outcome was diabetes incidence over a 4-year period, defined by fasting blood glucose ≥ 7.0 mmol/L or a new-onset oral hypoglycaemic or insulin prescription during the 4-year period. RESULTS The 4-year incidence of DM did not differ significantly between groups: 12.3%, 6.7%, and 11.9% in the atypical AP-exposed, atypical AP-unexposed, and control groups, respectively (χ(2) = 1.40, P = 0.50). Depression and antidepressant, cholinesterase inhibitor, and valproate use were independently associated with increases in fasting glucose. However, hyperglycaemia and hypoglycaemic prescriptions were not more common in geriatric psychiatric patients. CONCLUSIONS DM does not appear to be more common in geriatric psychiatric patients than similarly aged controls and is not more common in atypical AP users. However, depression and antidepressant, cholinesterase inhibitor, and valproate use may increase fasting glucose levels, and the clinical significance of this warrants further investigation. Nonetheless, given the rates of untreated and undertreated fasting hyperglycaemia in both our geriatric psychiatric and control samples (>10% of all patients), we recommend regular screening for DM in these populations.
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Affiliation(s)
- Roza Abitbol
- Faculty of Medicine, Laval University, Laval, Quebec, Canada
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A naturalistic comparison of the long-term metabolic adverse effects of clozapine versus other antipsychotics for patients with psychotic illnesses. J Clin Psychopharmacol 2014; 34:441-5. [PMID: 24943389 DOI: 10.1097/jcp.0000000000000159] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Clozapine, an evidence-based treatment of refractory schizophrenia, is associated with increased weight gain and metabolic dysregulation compared with most antipsychotics in short-term clinical trials. However, there are limited data describing comparative long-term metabolic risks. In this report, we examined whether short-term differences persist with long-term exposure to clozapine. METHODS The data of all patients in a university-based clinic with a psychotic illness or a mood disorder with psychotic features, based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis, and treated with an antipsychotic in calendar year 2012 were examined. A total of 307 patients met the criteria; 96 patients were treated with clozapine and the remaining 211 patients were treated with 1 or more non-clozapine antipsychotics. Body mass index, type 2 diabetes, hypertension, dyslipidemia, and obesity were compared. RESULTS The mean duration of the clozapine treatment was 7.6 years (range, 2 months to 21 y). On all metabolic measures, there were no statistically significant differences between the clozapine and non-clozapine groups (mean body mass index, 31 vs 32; type 2 diabetes, 17% vs 18%; dyslipidemia, 35% vs 38%; hypertension, 32% vs 39%; and obesity, 48% vs 54%). Removing the olanzapine-treated patients (n = 51) from the non-clozapine group did not change the findings. CONCLUSIONS In this university-based clinic sample with a large number of clozapine-treated patients, we found no evidence of increased risk in any individual measure for those receiving clozapine. Although speculative, the relative contribution of the increased short-term metabolic risk associated with clozapine may be diminished over time because multiple other variables likely also impact metabolic risk during the life span. Although speculative, the relative contribution of the increased short-term metabolic risk associated with clozapine may be diminished over time due to the accumulated impact of other variables that also impact metabolic risk across the life span.
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Bai YM, Su TP, Chen MH, Chen TJ, Chang WH. Risk of developing diabetes mellitus and hyperlipidemia among patients with bipolar disorder, major depressive disorder, and schizophrenia: a 10-year nationwide population-based prospective cohort study. J Affect Disord 2013; 150:57-62. [PMID: 23510547 DOI: 10.1016/j.jad.2013.02.019] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2012] [Revised: 02/07/2013] [Accepted: 02/07/2013] [Indexed: 12/20/2022]
Abstract
BACKGROUND The high comorbidity of metabolic side effects with severe mental disorders (SMDs), including bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia, had gained much attention, because the excess mortality of these patients is mainly due to physical illness. However, most of these studies were with cross-sectional study design, the time course of metabolic side effects and SMD cannot be elucidated without a cohort study. METHOD Using a nationwide database with a large sample size and a matched control cohort study design, we enrolled patients with SMDs but without diagnoses of and medications for DM and hyperlipidemia from 1996 to 2000, and followed them to the end of 2010. We compared them with age and gender-matched controls (1:4) for the incidence of DM and hyperlipidemia. RESULTS The identified cases were 367 patients with BD, 417 patients with MDD, and 1993 patients with schizophrenia, with average age of 45.3 ± 14.0, 46.5 ± 13.7, and 45.9 ± 12.3, respectively. The patients with BD and schizophrenia had increased risk of initiation of anti-diabetic medications (10.1% vs. 6.3%, p=0.012; 13.3% vs. 7.2% p<0.001; respectively), and anti-hyperlipidemia medications (15.8% vs.10.5%, p=0.004; 14.2% vs.12.1%, p=0.005; respectively) than the controls. After controlling age, gender, urbanization, and income, the Cox regression model showed significantly increased risk of initiation of anti-diabetic medications among patients with BD (hazard ratio (HR) of 1.702, 95% confidence interval (CI): 1.155-2.507) and schizophrenia (HR of1.793, 95% CI: 1.532-2.098). Increased risk of initiation of anti-hyperlipidemia medications was also noted among patients with BD (HR of 1.506, 95% CI: 1.107-2.047) and schizophrenia (HR of 1.154, 95% CI: 1.002-1.329). The patients with MDD did not show increased risk of initiation of these medications than the controls. CONCLUSIONS This first 10-year nationwide population-based prospective matched control cohort study showed increased risks of initiation of anti-diabetic and anti-hyperlipidemia medications among patients with BD and schizophrenia. No significant increased risk was noted among the patients with MDD.
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Affiliation(s)
- Ya-Mei Bai
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
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Abstract
To review the data with respect to prevalence of metabolic syndrome (MetS) and its correlates in schizophrenia. For this review, electronic search engines PUBMED, Sciencedirect, and Google Scholar were used. Available data suggests that most of the studies have been of cross-sectional design. Prevalence rates of MetS have varied from 11% to 69% in medicated patients, and 4-26% in drug naive patients in cross-sectional evaluations. Longitudinal studies have shown the prevalence rates to range from 0% to 14% at the baseline in drug naive patients, which increase to as high as 52.4% by 3 months of antipsychotic medication treatment. The prevalence rates of MetS in patients with schizophrenia are much higher than that seen in general population or healthy controls. Though there is no causal association with any demographic or clinical variables, the risk increases with increase in age. Among antipsychotics, there seems to be an association between MetS and atypical antipsychotics like clozapine and olanzapine. Therefore, the psychiatrists should be more vigilant regarding the presence of MetS in these high risk groups. Research on biological correlates of MetS in schizophrenia is still in its primitive stage, however, these is some evidence to suggest an association of MetS with adiponectin levels, hematological indices, methylenetetrahydrofolate reductase (MTHFR) and Alpha-1A adrenergic receptor (ADRA1A) gene. These areas hold promise, and targeting these with appropriate interventions may help us to prevent the occurrence of MetS in patients with schizophrenia in future.
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Affiliation(s)
- Nidhi Malhotra
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sandeep Grover
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Subho Chakrabarti
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Parmanand Kulhara
- Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Lee CP, Chen APJ, Juang YY. Weight Gain While Switching from Polypharmacy to Ziprasidone: A Case Report. ACTA ACUST UNITED AC 2013; 9:141-4. [PMID: 23644168 DOI: 10.3371/csrp.lech.043013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Second-generation antipsychotics (SGAs), valproate, and sulpiride are related to significant weight gain and risk of metabolic syndrome (MetS). Among SGAs, olanzapine and clozapine are associated with the highest metabolic risk while ziprasidone is among one of the SGAs with the lowest risk. Several reports suggest that weight loss is observed in switching other antipsychotics to ziprasidone. Here we describe a female patient with chronic paranoid schizophrenia who had an unexpected weight gain and developed MetS during a cross-switch from a polypharmacy of olanzapine, valproate and sulpiride to ziprasidone monotherapy.
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Kuo CJ, Yang SY, Liao YT, Chen WJ, Lee WC, Shau WY, Chang YT, Tsai SY, Chen CC. Second-generation antipsychotic medications and risk of pneumonia in schizophrenia. Schizophr Bull 2013; 39:648-57. [PMID: 22282455 PMCID: PMC3627761 DOI: 10.1093/schbul/sbr202] [Citation(s) in RCA: 107] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
This study assessed the association between second-generation antipsychotic medications and risk of pneumonia requiring hospitalization in patients with schizophrenia because the evidence is limited in the population. We enrolled a nationwide cohort of 33,024 inpatients with schizophrenia ranged in age from 18 to 65 years, who were derived from the National Health Insurance Research Database in Taiwan from 2000 to 2008. Cases (n = 1741) were defined as patients who developed pneumonia after their first psychiatric admissions. Risk set sampling was used to match each case with 4 controls by age, sex, and the year of the first admission based on nested case-control study. Antipsychotic exposure was categorized by type, duration, and daily dose, and the association between exposure and pneumonia was assessed using conditional logistic regression. We found that current use of clozapine (adjusted risk ratio = 3.18, 95% CI: 2.62-3.86, P < .001) was associated with a dose-dependent increase in the risk. Although quetiapine, olanzapine, zotepine, and risperidone were associated with increased risk, there was no clear dose-dependent relationship. Amisulpride was associated with a low risk of pneumonia. The use of clozapine combined with another drug (olanzapine, quetiapine, zotepine, risperidone, or amisulpride), as assessed separately, was associated with increased risk for pneumonia. In addition, with the exception of amisulpride, each drug was associated with increased risk for pneumonia at the beginning of treatment. Clinicians who prescribe clozapine to patients with schizophrenia should closely monitor them for pneumonia, particularly at the start of therapy and when clozapine is combined with other antipsychotics.
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Affiliation(s)
- Chian-Jue Kuo
- Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan,Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan,Department of Psychiatry, School of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Shu-Yu Yang
- Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan,Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ya-Tang Liao
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Wei J. Chen
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Wen-Chung Lee
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | | | - Yao-Tung Chang
- Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan
| | - Shang-Ying Tsai
- Department of Psychiatry, School of Medicine, Taipei Medical University, Taipei, Taiwan,These authors contributed equally to this study
| | - Chiao-Chicy Chen
- Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan,Department of Psychiatry, School of Medicine, Taipei Medical University, Taipei, Taiwan,These authors contributed equally to this study,To whom correspondence should be addressed; Taipei City Psychiatric Center, Taipei City Hospital, 309 Sung-Te Road, Taipei 110, Taiwan; tel: +886-2-2726-3141 ext. 1342, fax: +886-2-2728-5059, e-mail:
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Penckofer SM, Ferrans C, Mumby P, Byrn M, Emanuele MA, Harrison PR, Durazo-Arvizu RA, Lustman P. A psychoeducational intervention (SWEEP) for depressed women with diabetes. Ann Behav Med 2013; 44:192-206. [PMID: 22777878 DOI: 10.1007/s12160-012-9377-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Clinically significant depression is present in 25 % of individuals with type 2 diabetes, its risk being doubled in women. PURPOSE To examine the effectiveness of the Study of Women's Emotions and Evaluation of a Psychoeducational (SWEEP), a group therapy for depression treatment based on cognitive behavioral therapy principles that was developed for women with type 2 diabetes was conducted. METHODS Women with significantly elevated depression symptoms (Center for Epidemiologic Studies Depression Scale ≥16) were randomized to SWEEP (n = 38) or usual care (UC, n = 36). RESULTS Multilevel modeling indicated that SWEEP was more effective than UC in reducing depression (mean difference of -15 vs. -7, p < .01), decreasing trait anxiety (mean difference of -15 vs. -5, p < .01), and improving anger expression (mean difference of -12 vs. -5, p < .05). Although SWEEP and UC had improvements in fasting glucose (mean difference of -24 vs. -1 mg/dl) and HbA1c (mean difference of -0.4 vs. -0.1 %), there were no statistically significant differences between groups. CONCLUSIONS SWEEP was more effective than UC for treating depressed women with type 2 diabetes. Addition of group therapy for depression meaningfully expands the armamentarium of evidence-based treatment options for women with diabetes.
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Affiliation(s)
- Sue M Penckofer
- School of Nursing, Loyola University Chicago, Maywood, IL, USA.
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Hasnain M, Vieweg WVR, Hollett B. Weight gain and glucose dysregulation with second-generation antipsychotics and antidepressants: a review for primary care physicians. Postgrad Med 2012; 124:154-67. [PMID: 22913904 DOI: 10.3810/pgm.2012.07.2577] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Second-generation antipsychotics (SGAPs) and second-generation antidepressants (SGADs) have multiple US Food and Drug Administration-approved indications and are frequently prescribed by primary care physicians. We review the relative potential of these drugs to cause weight gain and glucose dysregulation, and offer clinical guidance to minimize and manage this risk. Among SGAPs, clozapine and olanzapine have a high risk for causing weight gain and glucose dysregulation; iloperidone, paliperidone, quetiapine, and risperidone have a medium risk; and aripiprazole, asenapine, lurasidone, and ziprasidone have a low risk. Young, drug-naïve patients are particularly vulnerable to weight gain associated with SGAPs. With the exception of clozapine, SGAPs have modest differences in their efficacy; however, their side effect profiles may influence selection. Using SGAPs with high metabolic liability conservatively and limiting their off-label use are important means to minimize risk. Patients should be screened before initiating any SGAP (or any antipsychotic medication) and monitored subsequently following standard guidelines, such as those provided by the American Diabetes Association. Healthy lifestyle counseling should be offered to all patients. Patients showing evidence of significant weight gain should be switched to an SGAP with a lower metabolic liability. Metformin may have some utility in young patients with limited exposure to antipsychotic drugs if lifestyle interventions fail and switching the SGAP is not an option. This option should be tried sooner than later for the best possible result. For SGADs, paroxetine and mirtazapine are associated with weight gain, and bupropion may cause modest weight loss. Other SGADs are mostly weight neutral, but individual variations may occur. Depression is associated with weight change and is a risk factor for glucose dysregulation. Treatment of depression improves glucose metabolism. We recommend that all patients taking SGADs be screened using anthropometric measures and metabolic assessment at baseline. Monitoring should be guided individually based on weight gain and other risk factors.
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Affiliation(s)
- Mehrul Hasnain
- Department of Psychiatry, Memorial University, St John's, Newfoundland, Canada.
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Lin WC, Winkelman JW. Obstructive sleep apnea and severe mental illness: evolution and consequences. Curr Psychiatry Rep 2012; 14:503-10. [PMID: 22872493 DOI: 10.1007/s11920-012-0307-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
Sleep complaints are commonly encountered in psychiatric clinics. Underlying medical disorders or sleep disorders need to be identified and treated to optimize treatment of the mental illness. Excessive daytime sleepiness, which is the main symptom of obstructive sleep apnea (OSA), overlaps with those of many severe mental illnesses. Medication side effects or the disorder itself maybe account for daytime sleepiness but comorbid OSA is a possibility that should not be overlooked. The diagnosis of OSA is straightforward but treatment compliance is problematic in psychiatric patients. This article summarizes studies concerning comorbid OSA in patients with severe mental illness and includes suggestions for future investigations.
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Affiliation(s)
- Wei-Chen Lin
- Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
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Coston AL, Hoffmann P, Equy V, Sergent F, Vidal C. [Fetal heart rate variability and clozapine treatment]. ACTA ACUST UNITED AC 2012; 40:549-52. [PMID: 22920232 DOI: 10.1016/j.gyobfe.2012.07.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2012] [Accepted: 05/16/2012] [Indexed: 10/28/2022]
Abstract
We report the 2 cases of schizophrenic patients with clozapine treatment and particularly, we underlined a reduced variability and low short-term variability, whereas biophysical ultrasound score, Dopplers and perception of fetal movements were acceptable and comfortable concerning the fetal vitality. Our aim is to show the limits of the analyzed fetal heart rate under clozapine. So, we may change our observation of fetus in chronic suffering that is usually mainly made with an informatics analysis of pregnants under clozapine.
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Affiliation(s)
- A-L Coston
- Service de gynécologie-obstétrique et médecine de la reproduction, hôpital Couple Enfant, université Joseph-Fourrier Grenoble 1, CHU de Grenoble, BP 217, 38043 Grenoble cedex 9, France.
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Pons i Villanueva A, Romero A, Goti J, Fernandez-Egea E, Undurraga J, Carne X, Bernardo M. Should obesity be a limiting factor for clozapine treatment? REVISTA DE PSIQUIATRIA Y SALUD MENTAL 2012; 6:75-9. [PMID: 23084801 DOI: 10.1016/j.rpsm.2012.05.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2012] [Revised: 05/23/2012] [Accepted: 05/24/2012] [Indexed: 10/28/2022]
Abstract
OBJECTIVE Clozapine is the first choice in drug-resistant schizophrenia but also causes important weight changes. This might discourage clinicians concerned about the risk of developing health problems. To assess this issue we measured change in body mass index (cBMI) induced by clozapine at 18 and 56 weeks. METHODS Baseline body weight and height were measured and weight weekly thereafter during the first 18 weeks of treatment. After that, measurements were made monthly. Steady clozapine dose, clozapine and norclozapine blood concentrations, concomitant medication, gender and age were recorded. RESULTS At 18 weeks (n=76) mean cBMI was 1.83 kg/m(2). Baseline BMI was inversely correlated with cBMI. At 56 weeks (n=57) cBMI was 2.67 kg/m(2) and was inversely correlated with basal BMI. Multiple regression analysis replicated the results. When split with BMI categories, obese patients had lesser risk for further weight gain. CONCLUSIONS Obesity should not discourage clinicians from starting clozapine in drug-resistant patients.
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Affiliation(s)
- Alexandre Pons i Villanueva
- Programa Esquizofrènia Clínic, Servei de Psiquiatria, Institut de Neurociències, Hospital Clínic de Barcelona. Barcelona, España
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Overturf MD, Overturf CL, Baxter D, Hala DN, Constantine L, Venables B, Huggett DB. Early life-stage toxicity of eight pharmaceuticals to the fathead minnow, Pimephales promelas. ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY 2012; 62:455-64. [PMID: 22048524 DOI: 10.1007/s00244-011-9723-6] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2011] [Accepted: 10/17/2011] [Indexed: 05/13/2023]
Abstract
Human pharmaceuticals are routinely being detected in the environment, and there is growing concern about whether these drugs could elicit effects on aquatic organisms. Regulatory paradigms have shifted accordingly, with a greater emphasis on chronic toxicity data compared with acute data. The Organisation for Economic Co-operation and Development 210 Early Life Stage Test has been proposed as a good measure of the potential for pharmaceuticals to elicit chronic toxicity. To begin building a data set regarding the early life-stage toxicity of pharmaceuticals to fish, fathead minnows (FHM) were exposed to amiodarone, carbamazepine, clozapine, dexamethasone, fenofibrate, ibuprofen, norethindrone, or verapamil. Survival and growth were used to assess chronic toxicity in FHM at 28 days posthatch. Exposure of FHM to carbamazepine, fenofibrate, and ibuprofen resulted in no significant adverse effects at the concentrations tested. FHM survival was not impacted by verapamil exposure; however, growth was significantly decreased at 600 μg/L. Dexamethasone-exposed FHM showed a significant decrease in survival at a concentration of 577 μg/L; however, growth was not impacted at the concentration tested. Norethindrone exposure resulted in a significant decrease in survival and dry weight at 14.8 and 0.74 μg/L, respectively. Exposure to amiodarone and clozapine resulted in a significant decrease in survival and a significant increase in growth at concentrations of 1020 and 30.8 μg/L, respectively. Although the effect levels derived in this study are greater then concentrations observed in the environment, these data suggest that synthetic progestins may require additional research.
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Affiliation(s)
- M D Overturf
- Department of Biology, University of North Texas, Denton, TX 76203, USA
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McEachin RC, Cavalcoli JD. Overlap of genetic influences in phenotypes classically categorized as psychiatric vs medical disorders. World J Med Genet 2011; 1:4-10. [DOI: 10.5496/wjmg.v1.i1.4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Psychiatric disorders have traditionally been segregated from medical disorders in terms of drugs, treatment, insurance coverage and training of clinicians. This segregation is consistent with the long-standing observation that there are inherent differences between psychiatric disorders (diseases relating to thoughts, feelings and behavior) and medical disorders (diseases relating to physical processes). However, these differences are growing less distinct as we improve our understanding of the roles of epistasis and pleiotropy in medical genetics. Both psychiatric and medical disorders are predisposed in part by genetic variation, and psychiatric disorders tend to be comorbid with medical disorders. One hypothesis on this interaction posits that certain combinations of genetic variants (epistasis) influence psychiatric disorders due to their impact on the brain, but the associated genes are also expressed in other tissues so the same groups of variants influence medical disorders (pleiotropy). The observation that psychiatric and medical disorders may interact is not novel. Equally, both epistasis and pleiotropy are fundamental concepts in medical genetics. However, we are just beginning to understand how genetic variation can influence both psychiatric and medical disorders. In our recent work, we have discovered gene networks significantly associated with psychiatric and substance use disorders. Invariably, these networks are also significantly associated with medical disorders. Recognizing how genetic variation can influence both psychiatric and medical disorders will help us to understand the etiology of the individual and comorbid disease phenotypes, predict and minimize side effects in drug and other treatments, and help to reduce stigma associated with psychiatric disorders.
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