|
1
|
Anozie IG, James BO, Omoaregba JO, Oriji SO, Erohubie PO, Enebe AC. Correlates of high-dose antipsychotic prescription amongst outpatients with Schizophrenia in a Nigerian Hospital. S Afr J Psychiatr 2022; 28:1791. [PMID: 35547105 PMCID: PMC9082254 DOI: 10.4102/sajpsychiatry.v28i0.1791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 02/22/2022] [Indexed: 11/18/2022] Open
Abstract
Background Treatment guidelines recommend the use of antipsychotic monotherapy at effective doses for the treatment of schizophrenia, although about a third of the sufferers still receive high-dose antipsychotic treatment. Current evidence suggests that high-dose antipsychotic prescription (HDAP) not only fails to improve outcomes but also increases side effects. Aim Our study aimed to determine the prevalence of HDAP and its association with illness severity, medication adherence behaviour and side effects amongst outpatients with schizophrenia. Setting The Federal Neuro-Psychiatric Hospital, Benin-City, Nigeria. Methods A cross-sectional study of 320 attendees with schizophrenia at the outpatient department was undertaken. We administered a sociodemographic and antipsychotic medication questionnaire, Mini-International Neuropsychiatric Interview, Positive and Negative Syndrome Scale, Liverpool University Neuroleptic Side Effects Rating Scales and Medication Adherence Rating Scales. High-dose antipsychotic prescription was determined by the ratio of prescribed daily dose to defined daily dose greater than 1.5. Results The prevalence of HDAP was 38.4%. Greater severity of illness, experiencing more side effects and poor medication adherence were significantly associated with HDAP.The major predictors of HDAP were antipsychotic polypharmacy and concurrent anticholinergic use. Conclusion We conclude that although the use of HDAP amongst patients with schizophrenia remains common, its persistent use should be discouraged.
Collapse
Affiliation(s)
- Ihechiluru G Anozie
- Department of Clinical Sciences, Federal Neuropsychiatric Hospital, Benin City, Nigeria
| | - Bawo O James
- Department of Clinical Sciences, Federal Neuropsychiatric Hospital, Benin City, Nigeria
| | - Joyce O Omoaregba
- Department of Clinical Sciences, Federal Neuropsychiatric Hospital, Benin City, Nigeria
| | - Sunday O Oriji
- Department of Clinical Sciences, Federal Neuropsychiatric Hospital, Benin City, Nigeria
- Department of Mental Health, Nnamdi Azikiwe University, Awka, Nigeria
| | - Paul O Erohubie
- Department of Clinical Sciences, Federal Neuropsychiatric Hospital, Benin City, Nigeria
- Department of Mental Health, Irrua Specialist Teaching Hospital, Irrua, Nigeria
| | - Anthony C Enebe
- Department of Clinical Sciences, Federal Neuropsychiatric Hospital, Benin City, Nigeria
- Department of Mental Health Services, Federal Medical Centre Asaba, Asaba, Nigeria
| |
Collapse
|
|
2
|
Li XQ, Tang XR, Li LL. Antipsychotics cardiotoxicity: What's known and what's next. World J Psychiatry 2021; 11:736-753. [PMID: 34733639 PMCID: PMC8546771 DOI: 10.5498/wjp.v11.i10.736] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 07/08/2021] [Accepted: 09/02/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic use of antipsychotic medications entails a dilemma between the benefit of alleviating psychotic symptoms and the risk of troubling, sometimes life-shortening adverse effects. Antipsychotic-induced cardiotoxicity is one of the most life-threatening adverse effects that raises widespread concerns. These cardiotoxic effects range from arrhythmia to heart failure in the clinic, with myocarditis/cardiomyopathy, ischemic injuries, and unexplained cardiac lesions as the pathological bases. Multiple mechanisms have been proposed to underlie antipsychotic cardiotoxicity. This review aims to summarize the clinical signs and pathological changes of antipsychotic cardiotoxicity and introduce recent progress in understanding the underlying mechanisms at both the subcellular organelle level and the molecular level. We also provide an up-to-date perspective on future clinical monitoring and therapeutic strategies for antipsychotic cardiotoxicity. We propose that third-generation antipsychotics or drug adjuvant therapy, such as cannabinoid receptor modulators that confer dual benefits - i.e., alleviating cardiotoxicity and improving metabolic disorders - deserve further clinical evaluation and marketing.
Collapse
Affiliation(s)
- Xiao-Qing Li
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Xin-Ru Tang
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Li-Liang Li
- Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| |
Collapse
|
|
3
|
Abstract
Healthcare in the twenty-first century has witnessed an increased use of prescription drugs. As a member of a patient's health care team, optometrists should be aware of the pharmaceuticals taken by patients and their potential ocular complications. This paper will discuss the most prescribed medications in Australia today and their effects on the visual system. The paper will review the agents used to treat six common systemic conditions, their frequency of use, mechanism of action, clinical indications, and potential ocular manifestations. Literature has documented both positive and negative associations of systemic medications on the eye's health. Many associations documented here have shown conflicting evidence, thus warranting further investigation. Based on the frequency and severity of the ocular manifestations in the literature, recommendations for clinical care are given. Being familiar with the most common ocular side effects associated with common systemic medications aids in the correct and timely diagnosis of ocular complications to prevent permanent sequelae.
Collapse
Affiliation(s)
- Rachel Williams
- University of Houston College of Optometry, Houston, United States
| | - Alex Hui
- School of Optometry and Vision Science, UNSW, Sydney, Australia
| |
Collapse
|
|
4
|
Late-Onset Cholestatic Liver Injury During Combination Treatment With Chlorpromazine and Olanzapine: A Case Report. J Clin Psychopharmacol 2019; 39:175-176. [PMID: 30640795 DOI: 10.1097/jcp.0000000000000999] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
|
|
5
|
A Population Pharmacokinetic and Pharmacodynamic Analysis of RP5063 Phase 2 Study Data in Patients with Schizophrenia or Schizoaffective Disorder. Eur J Drug Metab Pharmacokinet 2019; 43:573-585. [PMID: 29619682 PMCID: PMC6133081 DOI: 10.1007/s13318-018-0472-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Background and Objective RP5063 is a novel multimodal dopamine (D)–serotonin (5-HT) stabilizer possessing partial agonist activity for D2/3/4 and 5-HT1A/2A, antagonist activity for 5-HT2B/2C/7, and moderate affinity for the serotonin transporter. Phase 2 trial data analysis of RP5063 involving patients with schizophrenia and schizoaffective disorder defined: (1) the pharmacokinetic profile; and (2) the pharmacokinetic/pharmacodynamic relationships. Methods Pharmacokinetic sample data (175 patients on RP5063; 28 doses/patient) were analyzed, utilized one- and two-compartment models, and evaluated the impact of covariates. Pharmacodynamic analysis involved development of an Emax model. Results The pharmacokinetic analysis identified a one-compartment model incorporating body mass index influence on volume as the optimum construct, with fixed-effect parameters: (1) oral clearance (Cl/F), 5.11 ± 0.11 L/h; (2) volume of distribution (Vc/F), 328.00 ± 31.40 L; (3) absorption constant (ka) 0.42 ± 0.17 h−1; (4) lag time (t lag) of 0.41 ± 0.02 h; and (5) a calculated half-life of 44.5 h. Pharmacokinetics were linear related to dose. An Emax model for total Positive and Negative Syndrome Scale (PANSS) scores as the response factor against cumulative area under the curve (AUC) provided fixed-effect estimates: (1) Eo = 87.3 ± 0.71 (PANSS Units; pu); (2) Emax = − 31.60 ± 4.05 (pu); and (3) AUC50 = 89.60 ± 30.10 (µg·h/mL). The predicted PANSS improvement reflected a clinical dose range of 5–30 mg. Conclusions Pharmacokinetics of RP5063 behaved predictably and consistently. Pharmacodynamics were characterized using an Emax model, reflecting total PANSS score as a function of cumulative AUC, that showed high predictability and low variability when correlated with actual observations. Electronic supplementary material The online version of this article (10.1007/s13318-018-0472-z) contains supplementary material, which is available to authorized users.
Collapse
|
|
6
|
Cantillon M, Ings R, Bhat L. Initial Clinical Experience of RP5063 Following Single Doses in Normal Healthy Volunteers and Multiple Doses in Patients with Stable Schizophrenia. Clin Transl Sci 2018; 11:387-396. [PMID: 29637739 PMCID: PMC6039200 DOI: 10.1111/cts.12545] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 01/29/2018] [Indexed: 02/06/2023] Open
Abstract
RP5063 is a multimodal dopamine (D)‐serotonin (5‐HT) stabilizer with a high affinity for D2/3/4 and 5‐HT1A/2A/2B/7 receptors and moderate affinity for the serotonin transporter. Single‐dose (10 and 15 mg fasting, 15 mg fed) safety in healthy volunteers and multiple‐dose (10, 20, 50, and 100 mg fed, 10 days) safety and pharmacodynamics in patients with stable schizophrenia were defined in two phase I studies. In the single‐dose study, 32 treatment‐emergent adverse events (TEAEs) were observed. Orthostatic hypotension (n = 6), nausea (n = 5), and dizziness (n = 4) were the most common. One serious adverse event (SAE), seen in a patient who should not have been in the study due to a history of seizures, involved brief seizure‐like symptoms. In the multiple‐dose study, 75 TEAEs were reported. Akathisia (n = 20) and somnolence (n = 14) were the most frequent. No clinically significant changes were seen in glucose or prolactin levels, lipid profiles, weight, or electrocardiographic recordings. In both studies, all TEAEs resolved and none led to withdrawal from the study or death. A pharmacodynamic evaluation reflected significant improvements with RP5063 (P < 0.05) over placebo in an analysis of patients with a baseline Positive and Negative Syndrome Scale (PANSS) score ≥50 for positive subscale scores. Improvements of the Trail Making A and Trail Making B test results were observed for patients treated in the 50 mg dose group for days 5, 10, and 16. These findings indicate that RP5063 is well‐tolerated up to 100 mg and displays promising preliminary clinical behavioral and cognition activity signals in patients with stable disease over a 10‐day period.
Collapse
Affiliation(s)
- Marc Cantillon
- Reviva Pharmaceuticals, Inc., Sunnyvale, California, USA
| | - Robert Ings
- Reviva Pharmaceuticals, Inc., Sunnyvale, California, USA
| | | |
Collapse
|
|
7
|
Abstract
A wide spectrum of drugs can sometimes give rise to numerous adverse orofacial manifestations, particularly dry mouth, taste disturbances, oral mucosal ulceration, and/or gingival swelling. There are few relevant randomized double-blind controlled studies in this field, and therefore this paper reviews the data from case reports, small series, and non-peer-reviewed reports of adverse drug reactions affecting the orofacial region (available from a MEDLINE search to April, 2003). The more common and significant adverse orofacial consequences of drug therapy are discussed.
Collapse
Affiliation(s)
- C Scully
- Eastman Dental Institute for Oral Health Care Sciences, University College, University of London, 256 Gray's Inn Road, London WC1X 8LD, UK.
| | | |
Collapse
|
|
8
|
He X, Wu J, Jiang Y, Liu L, Ye W, Xue H, Montgomery W. Health care resource utilization and direct medical costs for patients with schizophrenia initiating treatment with atypical versus typical antipsychotics in Tianjin, China. BMC Health Serv Res 2015; 15:149. [PMID: 25880803 PMCID: PMC4419499 DOI: 10.1186/s12913-015-0819-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Accepted: 03/23/2015] [Indexed: 11/10/2022] Open
Abstract
Background It is uncertain whether the extra acquisition costs of atypical antipsychotics over typical antipsychotics are offset by their other reduced resource use especially in hospital services in China. This study compared the psychiatric-related health care resource utilization and direct medical costs for patients with schizophrenia initiating atypical or typical antipsychotics in Tianjin, China. Methods Data were obtained from the Tianjin Urban Employee Basic Medical Insurance database (2008–2010). Adult patients with schizophrenia with ≥1 prescription for antipsychotics after ≥90-day washout and 12-month continuous enrollment after first prescription was included. Psychiatric-related resource utilization and direct medical costs of the atypical and typical cohorts were estimated during the 12-month follow-up period. Logistic regressions, ordinary least square (OLS), and generalized linear models (GLM) were employed to estimate differences of resource utilization and costs between the two cohorts. One-to-one propensity score matching was conducted as a sensitivity analysis. Results 1131 patients initiating either atypical (N = 648) or typical antipsychotics (N = 483) were identified. Compared with the typical cohort, the atypical cohort had a lower likelihood of hospitalization (45.8% vs. 56.7%, P < 0.001; adjusted OR: 0.58, P < 0.001) over the follow-up period. Medication costs for the atypical cohort were higher than the typical cohort ($438 vs. $187, P < 0.001); however, their non-medication medical costs were significantly lower ($1223 vs. $1704, P < 0.001). The total direct medical costs were similar between the atypical and typical cohorts before ($1661 vs. $1892, P = 0.100) and after matching ($1711 vs. 1868, P = 0.341), consistent with the results from OLS and GLM models for matched cohorts. Conclusions The atypical cohort had similar total direct medical costs compared to the typical cohort. Higher medication costs associated with atypical antipsychotics were offset by a reduction in non-medication medical costs, driven by fewer hospitalizations.
Collapse
Affiliation(s)
- Xiaoning He
- School of Pharmaceutical Science and Technology, Tianjin University, No 92 Weijin Road, Nankai District, Tianjin, China.
| | - Jing Wu
- School of Pharmaceutical Science and Technology, Tianjin University, No 92 Weijin Road, Nankai District, Tianjin, China.
| | - Yawen Jiang
- Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, School of Pharmacy, University of Southern California, Los Angeles, CA, USA.
| | - Li Liu
- Lilly Suzhou Pharmaceutical Company, Ltd., Shanghai, China.
| | - Wenyu Ye
- Lilly Suzhou Pharmaceutical Company, Ltd., Shanghai, China.
| | - Haibo Xue
- Lilly Suzhou Pharmaceutical Company, Ltd., Shanghai, China.
| | | |
Collapse
|
|
9
|
Greenbaum L, Lerer B. Pharmacogenetics of antipsychotic-induced movement disorders as a resource for better understanding Parkinson's disease modifier genes. Front Neurol 2015; 6:27. [PMID: 25750634 PMCID: PMC4335175 DOI: 10.3389/fneur.2015.00027] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Accepted: 01/30/2015] [Indexed: 12/05/2022] Open
Abstract
Antipsychotic-induced movement disorders are major side effects of antipsychotic drugs among schizophrenia patients, and include antipsychotic-induced parkinsonism (AIP) and tardive dyskinesia (TD). Substantial pharmacogenetic work has been done in this field, and several susceptibility variants have been suggested. In this paper, the genetics of antipsychotic-induced movement disorders is considered in a broader context. We hypothesize that genetic variants that are risk factors for AIP and TD may provide insights into the pathophysiology of motor symptoms in Parkinson’s disease (PD). Since loss of dopaminergic stimulation (albeit pharmacological in AIP and degenerative in PD) is shared by the two clinical entities, genes associated with susceptibility to AIP may be modifier genes that influence clinical expression of PD motor sub-phenotypes, such as age at onset, disease severity, or rate of progression. This is due to their possible functional influence on compensatory mechanisms for striatal dopamine loss. Better compensatory potential might be beneficial at the early and later stages of the PD course. AIP vulnerability variants could also be related to latent impairment in the nigrostriatal pathway, affecting its functionality, and leading to subclinical dopaminergic deficits in the striatum. Susceptibility of PD patients to early development of l-DOPA induced dyskinesia (LID) is an additional relevant sub-phenotype. LID might share a common genetic background with TD, with which it shares clinical features. Genetic risk variants may predispose to both phenotypes, exerting a pleiotropic effect. According to this hypothesis, elucidating the genetics of antipsychotic-induced movement disorders may advance our understanding of multiple aspects of PD and it clinical course, rendering this a potentially rewarding field of study.
Collapse
Affiliation(s)
- Lior Greenbaum
- Department of Neurology, Sheba Medical Center at Tel Hashomer , Ramat Gan , Israel ; The Joseph Sagol Neuroscience Center, Sheba Medical Center at Tel Hashomer , Ramat Gan , Israel
| | - Bernard Lerer
- Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah - Hebrew University Medical Center , Jerusalem , Israel
| |
Collapse
|
|
10
|
Abstract
There is great concern over cardiovascular disease in the schizophrenic population owing to the high incidence of cardiovascular mortality. Increased cardiovascular mortality is related to lifestyle choices (e.g., smoking and sedentary lifestyle) and a high prevalence of comorbid medical conditions, including dyslipidemia, the metabolic syndrome and Type 2 diabetes. One factor that increases cardiovascular risk is the medications used to treat the core features of schizophrenia. Adverse cardiovascular effects of antipsychotic treatment have been recognized for many decades, especially tachycardia, orthostatic hypotension and rare instances of sudden death; but, since 2000, there has been a significant shift in the focus of risk perception. The older antipsychotic literature is replete with papers primarily concerned with the physiological consequences of muscarinic cholinergic antagonism, alpha(1)-adrenergic antagonism or receptors associated with cardiac conduction, but the current literature recognizes that, for most antipsychotic-exposed patients, the more significant cardiovascular burden of treatment is mediated by metabolic adverse effects such as weight gain, dyslipidemia and diabetes mellitus. The purpose of this review is to examine the cardiovascular risks of treatment with antipsychotic medications, elucidating relevant mechanisms and differences between various agents, especially for metabolic adverse effects seen with atypical antipsychotics.
Collapse
Affiliation(s)
- James W Michelsen
- University of California, San Diego, Department of Medicine, CA, USA.
| | | |
Collapse
|
|
11
|
Donnelly L, Rathbone J, Adams CE, Cochrane Schizophrenia Group. Haloperidol dose for the acute phase of schizophrenia. Cochrane Database Syst Rev 2013; 2013:CD001951. [PMID: 23983042 PMCID: PMC11622733 DOI: 10.1002/14651858.cd001951.pub2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND Haloperidol is a benchmark, accessible antipsychotic drug against which the effects of newer treatments are gauged. OBJECTIVES To determine the best range of doses for haloperidol for the treatment of people acutely ill with schizophrenia. SEARCH METHODS We searched the Cochrane Schizophrenia Group Trials Register (February 2010), which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. SELECTION CRITERIA We selected studies if they involved people being treated for acute schizophrenia, randomised to two or more dose ranges of non-depot haloperidol, and if they reported clinically meaningful outcomes. DATA COLLECTION AND ANALYSIS For this update, we inspected all citations and independently re-inspected a sample of citations in order to ensure reliable selection. We resolved any disagreement by discussion, and where doubt remained, we acquired the full-text article for further inspection. We then ordered papers, and reliably re-inspected and quality assessed the full reports, and extracted data. For homogeneous dichotomous data, we calculated the risk ratio (RR) with 95% confidence intervals (CI) on an intention-to-treat (ITT) basis. We assumed that people who left the study early or were lost to follow-up had a negative outcome. We calculated mean differences (MD) for continuous outcomes that reported ITT, last observation carried forward (LOCF) data. We excluded data if loss to follow-up was greater than 50%. MAIN RESULTS We included 19 trials with 19 different randomised dose comparisons. No studies reported data on relapse rates or quality of life and only one compared low dose (> 1.5 to 3 mg/day) haloperidol to higher dose ranges. Using standard lower dose (> 3 to 7.5 mg/day) did not result in loss of efficacy (no clinically important improvement in global state, versus standard higher dose (> 7.5 to 15 mg/day, n = 48, 1 RCT, RR 1.09, 95% CI 0.7 to 1.8, very-low-quality evidence); versus high dose (> 15 to 35 mg/day, n = 81, 2 RCTs, RR 0.95, 95% CI 0.8 to 1.2, very-low-quality evidence). Doses of haloperidol in the range of > 3 to 7.5 mg/day had a lower rate of development of clinically significant extrapyramidal adverse effects than higher doses (clinically significant extrapyramidal adverse effects, versus standard higher dose, n = 64, 2 RCTs, RR 0.12, 95% CI 0.01 to 2.1, very-low-quality evidence); versus high dose, n = 144, 3 RCTs, RR 0.59, 95% CI 0.5 to 0.8, very-low-quality evidence; versus very high dose (> 35 mg/day, n = 86, 2 RCTs, RR 0.70, 95% CI 0.5 to 1.1, very-low-quality evidence). None of the other comparisons between dose ranges yielded statistically significant differences, but several, particularly with lower dose ranges, were underpowered to detect clinically meaningful differences. AUTHORS' CONCLUSIONS Noresults were conclusive and all were based on small, short studies of limited quality. However, it would be understandable if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the lower dose ranges, especially > 1.5 to 3 mg/day.
Collapse
Affiliation(s)
- Lorna Donnelly
- NHS LothianCambridge Street House5‐7 Cambridge StreetEdinburghLothianUKEH1
| | - John Rathbone
- The University of SheffieldHEDS, ScHARRRegent Court30 Regent StreetSheffieldUKS1 4DA
| | - Clive E Adams
- The University of NottinghamCochrane Schizophrenia GroupInstitute of Mental HealthUniversity of Nottingham Innovation Park, Triumph Road,NottinghamUKNG7 2TU
| | | |
Collapse
|
|
12
|
Baptista PPA, de Senna PN, Paim MF, Saur L, Blank M, do Nascimento P, Ilha J, Vianna MRM, Mestriner RG, Achaval M, Xavier LL. Physical exercise down-regulated locomotor side effects induced by haloperidol treatment in Wistar rats. Pharmacol Biochem Behav 2013; 104:113-8. [DOI: 10.1016/j.pbb.2012.12.020] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Revised: 11/30/2012] [Accepted: 12/23/2012] [Indexed: 11/24/2022]
|
|
13
|
Bushong ME, Nakonezny PA, Byerly MJ. Subjective quality of life and sexual dysfunction in outpatients with schizophrenia or schizoaffective disorder. JOURNAL OF SEX & MARITAL THERAPY 2013; 39:336-346. [PMID: 23421823 DOI: 10.1080/0092623x.2011.606884] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
The objective of this research was to examine the association between sexual dysfunction and subjective quality of life in outpatients with schizophrenia and schizoaffective disorder. The authors evaluated a sample of 238 adult outpatients with diagnoses of schizophrenia or schizoaffective disorder who took quetiapine, olanzapine, or risperidone at study entry with a 1-time rating of the Arizona Sexual Experience Scale and the general life satisfaction scale item of the quality of life index. The authors used multiple linear robust regression and Spearman partial correlation coefficient to examine the relation between subjective quality of life (measured by the general life satisfaction scale item) and sexual functioning (measured by the Arizona sexual experience scale). The authors found a significant negative linear relation between the Arizona Sexual Experience Scale total score and the general life satisfaction scale item for the overall sample (r(s) = -0.16, p = .01), but not separately for men or women. Sexual dysfunction in men and women with schizophrenia and schizoaffective disorder is associated with decreased subjective quality of life, although the magnitude of the effect size was relatively small. Improving clinicians' awareness of the importance of sexual dysfunction in patients may improve tolerability and subsequent treatment outcomes.
Collapse
Affiliation(s)
- Mark E Bushong
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | | | | |
Collapse
|
|
14
|
Fernandes VS, Santos JR, Leão AH, Medeiros AM, Melo TG, Izídio GS, Cabral A, Ribeiro RA, Abílio VC, Ribeiro AM, Silva RH. Repeated treatment with a low dose of reserpine as a progressive model of Parkinson's disease. Behav Brain Res 2012; 231:154-63. [DOI: 10.1016/j.bbr.2012.03.008] [Citation(s) in RCA: 87] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Revised: 03/06/2012] [Accepted: 03/07/2012] [Indexed: 11/26/2022]
|
|
15
|
Greenbaum L, Lifschytz T, Zozulinsky P, Broner EC, Slonimsky A, Kohn Y, Lerer B. Alteration in RGS2 expression level is associated with changes in haloperidol induced extrapyramidal features in a mutant mouse model. Eur Neuropsychopharmacol 2012; 22:379-86. [PMID: 21982117 DOI: 10.1016/j.euroneuro.2011.09.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2011] [Revised: 08/10/2011] [Accepted: 09/10/2011] [Indexed: 11/30/2022]
Abstract
Antipsychotic induced Parkinsonism (AIP) is a common adverse effect of antipsychotic drug treatment among schizophrenia patients. Two previous studies showed association of the rs4606 SNP in the 3' untranslated region of the regulator of G protein signaling 2 gene (RGS2) with susceptibility to AIP. Since rs4606 reportedly influences expression of RGS2, we applied a translational approach and studied the effect of chronic (24 days) exposure to haloperidol on AIP-like features in mice carrying a mutation that causes lower Rgs2 gene expression. Haloperidol and vehicle treated male mice heterozygous (HET) or homozygous (HOM) for the mutation, or wild type (WT), were evaluated for open field locomotion, catalepsy duration, pole test performance and rota-rod latency to fall. We showed that in haloperidol treated mice lower Rgs2 expression is associated with better performance on the open field, catalepsy and rota-rod tests but not the pole test. Results were most consistent for the 0.2 mg/kg/d haloperidol dose. These observations support the possible involvement of RGS2 in mechanisms underlying susceptibility to AIP.
Collapse
Affiliation(s)
- Lior Greenbaum
- Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah – Hebrew University Medical Center, Jerusalem, Israel
| | | | | | | | | | | | | |
Collapse
|
|
16
|
Association of the ZFPM2 gene with antipsychotic-induced parkinsonism in schizophrenia patients. Psychopharmacology (Berl) 2012; 220:519-28. [PMID: 21947317 DOI: 10.1007/s00213-011-2499-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2011] [Accepted: 09/09/2011] [Indexed: 02/06/2023]
Abstract
RATIONALE Antipsychotic-induced parkinsonism (AIP) is a severe adverse affect of antipsychotic drug treatment. Recently, our group performed a genome-wide association study (GWAS) for AIP severity, and identified several potential AIP risk variants. OBJECTIVES The aim of this study was to validate our original AIP-GWAS susceptibility variants and to understand their possible function. METHODS We conducted a validation study of 15 single-nucleotide polymorphisms (SNPs) in an independent sample of 178 US schizophrenia patients treated for at least a month with typical or atypical antipsychotics. Then, a sample of 49 Jewish Israeli Parkinson's disease (PD) patients with available neuroimaging ([(123)I]-FP-CIT-SPECT) data was analyzed, to study association of confirmed AIP SNPs with level of dopaminergic deficits in the putamen. RESULTS Using logistic regression and controlling for possible confounders, we found nominal association of the intronic SNP, rs12678719, in the Zinc Finger Protein Multitype 2 (ZFPM2) gene with AIP (62 affected/116 unaffected), in the whole sample (p = 0.009; P = 5.97 × 10(-5) in the GWAS), and in the African American sub-sample (N = 111; p = 0.002). The same rs12678719-G AIP susceptibility allele was associated with lower levels of dopaminergic neuron related ligand binding in the contralateral putamen of PD patients (p = 0.026). CONCLUSIONS Our preliminary findings support association of the ZFPM2 SNP, rs12678719, with AIP. At the functional level, this variant is associated with deficits in the nigrostriatal pathway in PD patients that may be related to latent subclinical deficits among AIP-prone individuals with schizophrenia. Further validation studies in additional populations are required.
Collapse
|
|
17
|
Sedky K, Nazir R, Joshi A, Kaur G, Lippmann S. Which psychotropic medications induce hepatotoxicity? Gen Hosp Psychiatry 2012; 34:53-61. [PMID: 22133982 DOI: 10.1016/j.genhosppsych.2011.10.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2011] [Revised: 10/15/2011] [Accepted: 10/18/2011] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Safe prescribing practices to minimize pharmaceutically induced liver damage or worsening of preexisting conditions require knowledge about medicines with hepatotoxic potential. This paper reviews psychotropic medications and their effects on the liver. METHODS A MEDLINE search was performed utilizing the phrase "drug-induced liver injury" with various categories of psychiatric drugs. Only articles written in English were utilized. RESULTS Hepatotoxicity can be acute or chronic in nature. Medication discontinuation is necessary in acute forms, while close monitoring is required in milder forms of medication-induced chronic liver damage. Nefazodone, pemoline and/or tacrine are the highest offenders. Carbamazepine and valproate products (e.g., divalproex) can lead to this adverse event and should be avoided in patients with liver disease, persons with alcohol misuse or those consuming high doses of acetaminophen. CONCLUSION Knowing the risk levels associated with various medicines is important; prescribing multiple drugs with hepatotoxic effects should be avoided. One should educate patients about early warning signs of liver injury. Always provide clinical and laboratory monitoring before and during the use of hepatotoxic drugs. Clinical features and laboratory results govern medication prescribing with ongoing risk-to-benefit ratio assessment during pharmacotherapy.
Collapse
Affiliation(s)
- Karim Sedky
- Department of Psychiatry, Drexel University, Philadelphia, PA 19124, USA.
| | | | | | | | | |
Collapse
|
|
18
|
Drago A, Crisafulli C, Serretti A. The genetics of antipsychotic induced tremors: a genome-wide pathway analysis on the STEP-BD SCP sample. Am J Med Genet B Neuropsychiatr Genet 2011; 156B:975-86. [PMID: 21990027 DOI: 10.1002/ajmg.b.31245] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2011] [Accepted: 09/16/2011] [Indexed: 11/08/2022]
Abstract
Extrapyramidal symptoms (EPS) are associated with antipsychotic treatment. The exact definition of the genetic variants that influence the antipsychotic induced EPS would dramatically increase the quality of antipsychotic prescriptions. We investigated this issue in a subsample of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Four hundred nine manic patients were treated with antipsychotics and had complete clinical and genetic data. Outcome was an item of the Clinical Monitoring Form which scored tremors from 0 to 4 at each clinical visit. Visits were scheduled according to clinical issues, based on a naturalistic approach. A genomic inflation factor of 1.017 resulted after genetic quality control. Single SNPs GWAS (Plink) and molecular pathway GWAS were conducted (SNP ratio test, KEGG depository). No single SNP reached GWAS significance level of association. Molecular pathways related to cell survival events and lipid synthesis were significantly associated with antipsychotic induced EPS (P = 0.0009 for Hsa04512, Hsa01031, Hsa00230, Hsa04510, Hsa03320, Hsa04930, and Hsa04115; P = 0.0019 for Hsa04020 and Hsa00561). This finding was consistent with previous GWAS studies.
Collapse
Affiliation(s)
- Antonio Drago
- Institute of Psychiatry, University of Bologna, Bologna, Italy
| | | | | |
Collapse
|
|
19
|
Abstract
Orthostatic hypotension is a common adverse effect of antipsychotics that may delay or prevent titration to a dose necessary to control psychotic symptoms. Complications of orthostatic hypotension include syncope, transient ischaemic attack, stroke, myocardial infarction and death. The risk of orthostatic hypotension associated with antipsychotic therapy is increased in patients with disorders of the autonomic nervous system, fluid imbalance and those taking concomitant drug therapy that affects haemodynamic tone. Prospective monitoring for changes in postural blood pressure is important because patients with psychotic disorders often do not articulate symptoms of orthostasis and the subjective report of dizziness does not correlate well with orthostatic blood pressure changes. Nonpharmacological strategies and patient education, most notably, slowly rising from the supine position, are crucial first steps in the prevention and treatment of both symptomatic and asymptomatic orthostatic hypotension. Pharmacological treatment is only recommended when symptomatic orthostatic hypotension persists despite proper nonpharmacological therapy and there is a compelling indication for antipsychotic treatment. Fludrocortisone is a reasonable first choice for symptomatic orthostatic hypotension. Other agents including desmopressin and midodrine may be considered in patients who do not respond favourably to a trial of fludrocortisone, but safety concerns and lack of evidence limit the utility of these agents.
Collapse
Affiliation(s)
- James J Gugger
- Department of Clinical Pharmacy Practice, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, New York, USA.
| |
Collapse
|
|
20
|
Synergism of theophylline and anticholinergics to inhibit haloperidol-induced catalepsy: a potential treatment for extrapyramidal syndromes. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34:1465-71. [PMID: 20713114 DOI: 10.1016/j.pnpbp.2010.08.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2010] [Revised: 07/20/2010] [Accepted: 08/06/2010] [Indexed: 11/19/2022]
Abstract
Extrapyramidal syndromes (EPS) impose a heavy burden on patients receiving antipsychotic therapy. Anticholinergics are the drugs of choice for preventing EPS, but they also produce many adverse reactions. Using the EPS model of haloperidol-induced catalepsy we evaluated the potential therapeutic value of a mixture of low doses of the non-selective adenosine antagonist theophylline (0.93 and 1.86 mg/kg), and the muscarinic antagonists benztropine (0.134 and 0.268 mg/kg) and ethopropazine (0.116 and 0.232 mg/kg). In rats pretreated with vehicle (distilled water), the cumulative catalepsy time over 5 h was 4199±228 s, and the mean latency was 67.5±7.8 min. Applied separately, neither of the drugs at the doses used caused significant changes of catalepsy intensity vs. control rats. However, the combination of the larger doses of theophylline and benztropine caused a significant reduction of catalepsy intensity (-41±10%) compared with the effects of the vehicle, vs. the lower dose of benztropine, and vs. both doses of theophylline alone. The mixture of the larger doses of theophylline and benztropine also delayed catalepsy onset (156±21 min) as compared with the lower doses of these same drugs applied alone. In the case of theophylline plus ethopropazine, only the association of the larger doses showed a non-significant tendency to inhibit catalepsy (-21±8%) and to prolong its latency (108±13 min). Further, neither catalepsy intensity nor its latency was affected by a combination of the selective A(1)R antagonist DPCPX (1 mg/kg), with the larger doses of both anticholinergics. In contrast, the anticholinergics showed synergism with a subthreshold dose of the selective A(2A)R antagonist ZM 241395 (0.5 mg/kg), causing a significant reduction of catalepsy intensity (ethopropazine, -27±5%; benztropine, -35±9%) and prolonging its latency (ethopropazine, 65±9 min; benztropine, 78±11 min), compared with the effect of their respective vehicle (DMSO plus mineral oil: catalepsy time, 5100±196 s; latency, 17.5±2.5 min). These findings suggest that neuroleptic-induced EPS could be effectively controlled by a combination of lower doses of theophylline and anticholinergics, with the advantage of maximizing their efficacy and minimizing their adverse reactions.
Collapse
|
|
21
|
Neutropenia as a class effect of antipsychotic agents: a case report. J Clin Psychopharmacol 2010; 30:639-40. [PMID: 20841965 DOI: 10.1097/jcp.0b013e3181f100d4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
22
|
Abstract
All psychotropic medications have the potential to induce numerous and diverse unwanted ocular effects. Visual adverse effects can be divided into seven major categories: eyelid and keratoconjunctival disorders; uveal tract disorders; accommodation interference; angle-closure glaucoma; cataract/pigmentary deposits in the lens and cornea; retinopathy; and other disorders. The disorders of the eyelid and of the keratoconjunctiva are mainly related to phenothiazines and lithium. Chlorpromazine, at high dosages, can commonly cause abnormal pigmentation of the eyelids, interpalpebral conjunctiva and cornea. It can also cause a more worrisome but rarer visual impairment, namely corneal oedema. Lithium can rarely lead to a bothersome eye irritation by affecting sodium transport. Uveal tract problems are mainly associated with tricyclic antidepressants (TCAs), typical antipsychotics, topiramate and selective serotonin reuptake inhibitors (SSRIs). TCAs, typical antipsychotics and SSRIs can all cause mydriasis that is often transient and with no major consequences, but that can promote closure of angles in susceptible patients. Topiramate has been frequently associated with a number of significant ocular symptoms including acquired myopia and angle-closure glaucoma. Problems with accommodation are related to TCAs and to low-potency antipsychotics. TCAs cause transient blurred vision in up to one-third of patients. Angle-closure glaucoma is a serious condition that has been mainly associated with TCAs, low-potency antipsychotics, topiramate and, to a lesser extent, SSRIs. When patients with narrow angles are given TCAs, they all appear to experience induction of glaucomatous attacks. Antipsychotics and SSRIs may lead to an added risk of developing angle-closure glaucoma, but only in predisposed eyes. Topiramate can lead to an allergic-type reaction whereby structures of the lens and ciliary body are displaced, which results in angle-closure glaucoma. Cataractous changes can result from antipsychotics, mainly from high dosages of chlorpromazine or thioridazine. These two drugs, when used at high dosages and for prolonged periods, frequently cause lenticular opacifications. Retinopathy has been shown to be related to high dosages of typical antipsychotics, mainly chlorpromazine and thioridazine. The frequency of occurrence of retinal effects seems to be proportional to the total amount of drug used over a long period of time. Other visual problems of special concern are the ocular dystonias, other eye movement disorders, and decreased ability to perceive colours and to discriminate contrast. Ocular dystonias can occur with antipsychotics (especially high-potency ones), carbamazepine (especially in polytherapy), topiramate and, rarely, with SSRIs. Disturbance in various eye movements is frequently seen with benzodiazepines, antiepileptic drugs and lithium. Impairment in the perception of colours and the discrimination of contrasts has been shown to occur not uncommonly with carbamazepine and lorazepam. Thus, typical antipsychotics, TCAs, lithium, benzodiazepines, carbamazepine, topiramate and SSRIs appear to produce most of the currently recognized ocular problems. Psychiatrists, ophthalmologists and patients need to be aware of and prepared for any medication-induced adverse effect. Early prevention and intervention can avoid most of the serious and potentially irreversible ocular toxicities.
Collapse
Affiliation(s)
- Sami Richa
- Department of Psychiatry, Psychiatric Hospital of the Cross, Beirut, Lebanon.
| | | |
Collapse
|
|
23
|
Townsend L, Findling RL. Modifying the risk of atypical antipsychotics in the treatment of juvenile-onset schizophrenia. Expert Opin Pharmacother 2010; 11:195-205. [PMID: 20088741 DOI: 10.1517/14656560903473165] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
IMPORTANCE TO THE FIELD This review summarizes the evidence for use of typical and atypical antipsychotic medications for the treatment of juvenile-onset schizophrenia. We highlight the risks and benefits of antipsychotic agents for youth with this disorder, paying special attention to weight gain and metabolic effects, an area of specific concern within child and adolescent psychiatry. AREAS COVERED IN THIS REVIEW We describe the seriousness of juvenile-onset schizophrenia and its impact on long-term functioning, noting that pharmacological treatment remains the standard of care for this disorder. We focus on weight gain and metabolic effects associated with atypical agents and review strategies to modify risks associated with these agents. WHAT THE READER WILL GAIN We summarize strategies for attenuating the risk of weight gain for youth on atypical antipsychotics, including what is known about nutritional counseling and exercise programs as well as pharmacotherapy with adjunctive weight loss agents. TAKE-HOME MESSAGE Given the negative consequences associated with untreated schizophrenia, it appears that the most effective way to improve the risk:benefit ratio in the treatment of adolescents with schizophrenia is to reduce the risks associated with pharmacological treatment.
Collapse
Affiliation(s)
- Lisa Townsend
- Rutgers University School of Social Work, Center for Education and Research on Mental Health Therapeutics, 536 George Street, New Brunswick, NJ 08901, USA
| | | |
Collapse
|
|
24
|
The association between class of antipsychotic and rates of hospitalization: Results of a retrospective analysis of data from the 2005 medicare current beneficiary survey. Clin Ther 2009; 31:2931-9. [DOI: 10.1016/j.clinthera.2009.12.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2009] [Indexed: 11/19/2022]
|
|
25
|
Genome-wide association study of antipsychotic-induced parkinsonism severity among schizophrenia patients. Psychopharmacology (Berl) 2009; 206:491-9. [PMID: 19680635 DOI: 10.1007/s00213-009-1627-z] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2009] [Accepted: 07/15/2009] [Indexed: 10/20/2022]
Abstract
RATIONALE Antipsychotic-induced parkinsonism (AIP) is a severe adverse affect of neuroleptic treatment. Interindividual heterogeneity in AIP development and severity is associated with risk factors such as antipsychotic drug type, old age, and female gender. There is evidence for genetic predisposition to develop AIP but the variants that confer susceptibility or protection are mostly unknown. OBJECTIVE To identify genes related to AIP susceptibility, we performed a pharmacogenomic genome-wide association study (GWAS) for AIP severity. METHODS Three hundred ninety-seven American schizophrenia patients who participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)-GWAS project were included in our analysis. Patients had been randomized to treatment with antipsychotic monotherapy for periods ranging from 2 weeks to 18 months during phase 1 of the CATIE trial. They were regularly assessed for AIP severity using the modified Simpson-Angus Scale (SAS). For statistical analysis, patients were dichotomized as cases (average SAS mean global score > 0.3 during CATIE phase 1, N = 199) or controls (average SAS mean global score 0, N = 198). RESULTS Using logistic regression and controlling for population stratification, age, gender, SAS score at baseline, and concomitant use of anticholinergic drugs, we identified several single-nucleotide polymorphisms associated with AIP severity. Although none reached the GWAS significance level of P < 4.2 x 10(-7), some promising candidate genes for further research on genetic predisposition to AIP were identified including EPF1, NOVA1, and FIGN. CONCLUSIONS Our finding may contribute to understanding of the pathophysiology of AIP as well as to a priori identification of patients vulnerable for development of AIP.
Collapse
|
|
26
|
van Bruggen M, van Amelsvoort T, Wouters L, Dingemans P, de Haan L, Linszen D. Sexual dysfunction and hormonal changes in first episode psychosis patients on olanzapine or risperidone. Psychoneuroendocrinology 2009; 34:989-95. [PMID: 19264412 DOI: 10.1016/j.psyneuen.2009.01.013] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2008] [Revised: 01/23/2009] [Accepted: 01/28/2009] [Indexed: 11/15/2022]
Abstract
Atypical antipsychotics interfere with central and peripheral neurotransmitter systems and with hormonal production. In this study we compared the effect of olanzapine and risperidone on hormonal state and sexual function (by using the Questionnaire for Sexual Dysfunction, QSD) in 40 patients with a first episode psychosis. Results were compared to those of 34 healthy controls. Patients using risperidone had significant higher prolactin levels than patients using olanzapine. Patients using olanzapine had significantly higher 17beta-estradiol levels than patients using risperidone. Overall satisfaction with sexuality was less in patients compared to controls, but not different between patients using olanzapine and those using risperidone. Problems with sexual arousal were significantly higher in patients using olanzapine compared to patients using risperidone. A significantly higher frequency of problems with ejaculation and problems with insensibility of genitals were found in patients compared to healthy controls. We found no relation between medication, prolactin and 17beta-estradiol levels, frequency of sexual activity, overall satisfaction with sexuality and any of the 18 sexual dysfunctions we investigated. Our results suggests that sexual dysfunction in patients with first episode psychosis might occur despite normal prolactin levels. Also, sexual dysfunction is highly prevalent in healthy controls. Awareness should be raised of potential sexual problems in young adults.
Collapse
Affiliation(s)
- Marion van Bruggen
- Department of Psychiatry, AMC University of Amsterdam, Meibergdreef 5, 1105 AZ Amsterdam, The Netherlands.
| | | | | | | | | | | |
Collapse
|
|
27
|
Abstract
Many patients with skin disorders have psychologic issues associated with their chief complaints. Dermatologists who wish to help their patients with psychodermatologic conditions can greatly enhance their therapeutic armamentarium by becoming familiar with the use of a few selected psychotropic agents. This paper will review the current status and future directions of psychopharmacology for the major types of psychopathologies encountered in a dermatology practice (depression, obsessive-compulsive disorder, anxiety, and delusional disorder) with the intent of guiding dermatologists in the choice of a psychotropic agent for patients with psychologic component to their skin disorder.
Collapse
Affiliation(s)
- Chai Sue Lee
- Department of Dermatology, University of California, Davis School of Medicine, Sacramento, California 95816, USA.
| | | | | | | |
Collapse
|
|
28
|
Luft B, Taylor D. A review of atypical antipsychotic drugs versus conventional medication in schizophrenia. Expert Opin Pharmacother 2007; 7:1739-48. [PMID: 16925501 DOI: 10.1517/14656566.7.13.1739] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Atypical antipsychotics are replacing conventional antipsychotics for the treatment of schizophrenia. They are considered to be at least as effective as conventional agents, with most producing fewer extrapyramidal symptoms. This review presents the evidence from published meta-analyses and describes differences in clinical effectiveness and tolerability between conventional and atypical antipsychotic agents. In addition, it discusses some of the more significant adverse effects including tardive dyskinesia, weight gain, diabetes and sudden death. Results from meta-analyses are conflicting, with some finding no significant advantages on measures of efficacy or tolerability for atypical antipsychotics over moderate daily doses of conventional drugs. Other results have shown that some atypical drugs have at least minor efficacy advantages over conventional comparators. Atypical antipsychotics exhibit a much reduced risk for tardive dyskinesia compared with conventional drugs. However, weight gain is more common with some atypical drugs (especially clozapine and olanzapine). Both conventional and atypical antipsychotics have been associated with diabetes, with most reports implicating both clozapine and olanzapine. Finally, atypical antipsychotics (unlike conventional drugs) have little or no effect on QT and are not associated with sudden death.
Collapse
Affiliation(s)
- Barrat Luft
- Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, G12 OXH, UK.
| | | |
Collapse
|
|
29
|
Delieu JM, Horobin RW, Duguid JK. Formation of immature neutrophil leucocytes in schizophrenic patients treated with various antipsychotic drugs: comparisons and predictions. J Psychopharmacol 2006; 20:824-8. [PMID: 16401649 DOI: 10.1177/0269881106061112] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The neutrophils of schizophrenic patients taking antipsychotic drugs were evaluated. Neutrophil immaturity was assessed by determining mean nuclear lobe number in peripheral blood smears of patients and controls. Subjects were patients medicated with typical (upenthixol (n 6), uphenazine (n 7), haloperidol (n 23), thioridazine (n 15), and triuoperazine (n 6)) or atypical (olanzapine (n 15), risperidone (n 10), and sulpiride (n 7)) antipsychotic drugs. Controls (n 58) were healthy, non-medicated clinical and academic staff. Mean lobe number was determined using light microscopy and examining 300 neutrophils per individual. For subject and control groups, means and medians of mean lobe numbers, and also mean white cell and neutrophil counts, were determined. Means for each group were compared using the Mann-Whitney U test; variances using F ratios. Mean lobe numbers of all patients were decreased compared to controls. The left shift occurring in patients medicated with haloperidol, olanzapine, risperidone, thioridazine, and triuoperazine was signícantat P 0.0001; for upenthixol P 0.001, and for sulpiride P 0.05. The left shift for uphenazine was not statistically signíant. For one patient, mean lobe numbers were obtained before and after medication with olanzapine commenced, and a lowering of mean lobe number was seen. Although the coefficient of variation in the patient groups was large compared to the controls, nevertheless more than half of the patients had mean lobe numbers outside the observed range of values seen in the control population. White blood cell and neutrophil counts in patients and controls were not signiécantly different. This study demonstrated that patients taking antipsychotic drugs have immature neutrophils, but normal total white cell and neutrophil numbers. The effect was seen with both typical and atypical antipsychotic drugs, and is probably drug-induced. It is possible that mean lobe number may predict patients at risk from neutropenia or agranulocytosis, as is also suggested by an analysis of the relative numbers of literature reports of neutrophil pathology for these drugs. It is of interest that olanzapine, which has been considered a haematologically non-hazardous drug, was shown to be associated with a significant decrease in mean lobe number.
Collapse
Affiliation(s)
- J M Delieu
- University of Wales, Bangor, School of Radiography, Faculty of Health Studies, Wrexham, UK.
| | | | | |
Collapse
|
|
30
|
Rettenbacher MA, Baumgartner S, Eder-Ischia U, Edlinger M, Graziadei I, Hofer A, Huber R, Hummer M, Kemmler G, Weiss E, Fleischhacker WW. Association between antipsychotic-induced elevation of liver enzymes and weight gain: a prospective study. J Clin Psychopharmacol 2006; 26:500-3. [PMID: 16974192 DOI: 10.1097/01.jcp.0000236654.85791.ae] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
We conducted a prospective, open study in schizophrenia patients treated with second-generation antipsychotics in order to investigate the risk for elevation of liver enzymes and its correlation to antipsychotic-induced weight gain. Body mass index, serum transaminases, plasma serum levels of the antipsychotic used, and blood cell counts were measured weekly during the first 6 weeks of treatment and monthly thereafter. A considerable proportion of subjects showed an increase beyond normal levels of at least one of the measured transaminases. In all but one case, the elevation of liver enzymes was transient. We found a statistically significant correlation between weight gain and liver enzyme elevation. The group of patients that had gained at least 7% of the baseline body weight showed significantly higher increases of transaminases as compared with those who had gained less than 7% weight. We conclude that antipsychotic-induced elevation of liver enzymes is mostly transient and could be associated with weight gain.
Collapse
Affiliation(s)
- Maria A Rettenbacher
- Department of Biological Psychiatry, Medical University Innsbruck, Anichstrasse, Innsbruck, Austria.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Costa AMN, Lima MSD, Mari JDJ. A systematic review on clinical management of antipsychotic-induced sexual dysfunction in schizophrenia. SAO PAULO MED J 2006; 124:291-7. [PMID: 17262163 PMCID: PMC11068300 DOI: 10.1590/s1516-31802006000500012] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2005] [Accepted: 09/19/2006] [Indexed: 04/07/2023] Open
Abstract
INTRODUCTION Sexual dysfunction frequently occurs in patients with schizophrenia under antipsychotic therapy, and the presence of sexual side effects may affect compliance. The aim of this study was to review and describe clinical findings relating to the appropriate management of such dysfunctions. MATERIAL AND METHODS The research was carried out through Medline (from 1966 to March 2005), PsycInfo (from 1974 to March 2005), and Cochrane Library (from 1965 to March 2005) and included any kind of study, from case reports to randomized trials. RESULTS The most common sexual dysfunctions found in the literature were libido decrease, difficulties in achieving and maintaining erection, ejaculatory dysfunction, orgasmic dysfunction, and menstrual irregularities. Thirteen papers were found: eight of them were open-label studies, four were descriptions of cases, and only one was a randomized clinical trial. All of them were short-term and had small sample sizes. The agents used were: bromocriptine, cabergoline, cyproheptadine, amantadine, shakuyaku-kanzo-to, sildenafil and selegiline. DISCUSSION There was no evidence that those agents had proper efficacy in treating the antipsychotic-induced sexual dysfunction. An algorithm for managing sexual dysfunction induced by antipsychotics is suggested as a support for clinical decisions. Since the outcome from schizophrenia treatment is strongly related to compliance with the antipsychotics, prevention of sexual dysfunction is better than its treatment, since there is a scarcity of data available regarding the efficacy of intervention to deal with these problems.
Collapse
|
|
32
|
Tollefson GD, Taylor CC. Olanzapine: Preclinical and Clinical Profiles of a Novel Antipsychotic Agent. CNS DRUG REVIEWS 2006. [DOI: 10.1111/j.1527-3458.2000.tb00155.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
|
|
33
|
Carnahan RM, Lund BC, Perry PJ, Chrischilles EA. Increased risk of extrapyramidal side-effect treatment associated with atypical antipsychotic polytherapy. Acta Psychiatr Scand 2006; 113:135-41. [PMID: 16423165 DOI: 10.1111/j.1600-0447.2005.00589.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
OBJECTIVE To determine whether atypical antipsychotic polytherapy is a risk factor for drug treatment for extrapyramidal side-effects (anti-EPS drugs) and whether the risk is attributable to antipsychotic dose. METHOD We studied Iowa Medicaid beneficiaries aged 18-64 years with an active atypical and no conventional antipsychotic on January 1, 2001. The association of atypical antipsychotic polytherapy with anti-EPS drug treatment was determined. Multiple logistic regression was utilized to adjust for covariates in two models, the first adjusting for age, sex and the specific antipsychotic(s) prescribed, and the second also adjusting for doses. RESULTS Among 4400 patients, the unadjusted odds of anti-EPS treatment were increased two-fold with polytherapy. Polytherapy remained a risk factor in the first model (OR 1.5, 95% CI 1.1-2.0), but not after adjusting for doses (OR 1.0, 95% CI 0.7-1.4). CONCLUSION Atypical antipsychotic polytherapy is a risk factor for anti-EPS drug treatment, apparently because of higher cumulative doses.
Collapse
Affiliation(s)
- R M Carnahan
- Department of Pharmacy: Clinical and Administrative Sciences, The University of Oklahoma College of Pharmacy, Tulsa, OK 74135, USA.
| | | | | | | |
Collapse
|
|
34
|
Abstract
Many patients who have skin disorders have associated psychosocial issues. Psychotropic agents with improved side-effect profiles are available to allow physicians who are not psychiatrists to manage patients who have psychiatric conditions with agents that are effective, simple to administer, and generally well tolerated. Dermatologists who wish to help their patients who have psychodermatologic conditions can enhance their armamentarium by becoming familiar with the use of a few selected psychotropic agents. This article reviews the current status and future directions of psychopharmacology for the major types of psychopathologies encountered in dermatology practice.
Collapse
Affiliation(s)
- Chai Sue Lee
- Department of Dermatology, University of California Davis Medical Center, Sacramento, California 94118, USA
| | | |
Collapse
|
|
35
|
Byerly MJ, Lescouflair E, Weber MT, Bugno RM, Fisher R, Carmody T, Varghese F, Rush AJ. An open-label trial of quetiapine for antipsychotic-induced sexual dysfunction. JOURNAL OF SEX & MARITAL THERAPY 2004; 30:325-332. [PMID: 15672600 DOI: 10.1080/00926230490465082] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
This study evaluated the effect of switching outpatients with schizophrenia and antipsychotic-induced sexual dysfunction to open-label quetiapine treatment. Secondary objectives were to compare the antipsychotic and prolactin-related effects of quetiapine versus prestudy antipsychotic treatment. Eight patients with at least moderately severe antipsychotic-induced sexual dysfunction (N = 7 taking risperidone, 4-6 mg/d; N = 1 taking haloperidol, 10 mg/d) were evaluated prospectively after they switched to 6 weeks of quetiapine treatment. The assessments that we used included evaluations of sexual functioning (Arizona Sexual Experience Scale [ASEX]; McGahuey et al., 2000), psychopathology (Positive and Negative Syndrome Scale [PANSS]; Kay, Fiszbeinm, & Opler, 1997), adverse events, and plasma prolactin levels. Quetiapine was associated with clinically and statistically significant improvement in ASEX total scores (p = 0.008) and significantly decreased PANSS total scores (p = 0.03). Plasma prolactin levels tended to decrease after the transition to quetiapine (p = 0.09). Quetiapine appears to offer an option to reduce antipsychotic-induced sexual dysfunction for outpatients with schizophrenia.
Collapse
Affiliation(s)
- Matthew J Byerly
- University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9101, USA.
| | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Kinon BJ, Jeste DV, Kollack-Walker S, Stauffer V, Liu-Seifert H. Olanzapine treatment for tardive dyskinesia in schizophrenia patients: a prospective clinical trial with patients randomized to blinded dose reduction periods. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28:985-96. [PMID: 15380859 DOI: 10.1016/j.pnpbp.2004.05.016] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/10/2004] [Indexed: 11/16/2022]
Abstract
BACKGROUND Tardive dyskinesia (TD) is a potentially persistent and disabling abnormal involuntary movement disorder. The aim of this 8-month study was to determine if olanzapine treatment could lead to a significant and persistent reduction in preexisting TD. METHODS Eligible schizophrenia patients met restricted Research Diagnosis criteria of TD requiring, in part, a rating of at least moderate severity (score > or = 3) in one or more of seven body regions on the Abnormal Involuntary Movement Scale (AIMS). Patients received olanzapine, 5-20 mg/day, for 8 months. During this period, they underwent one to two dose reduction periods under blinded conditions. Concurrent changes in TD, psychopathology, parkinsonism and akathisia were assessed with the AIMS, the Positive and Negative Syndrome Scale (PANSS), and the Simpson-Angus and Barnes Akathisia Scales, respectively. RESULTS A significant reduction in mean AIMS total score was demonstrated at endpoint (n = 92; p < 0.001) as well as at each visit (p < 0.001) and as early as Week 1 on olanzapine. Approximately 70% of patients no longer met the restricted Research Diagnostic criteria for persistent TD (RD-TD) after 8 months of treatment. No statistically significant rebound worsening of TD was found during either blinded drug reduction period. Significant improvement in psychopathology (p = 0.001) and parkinsonism (p < 0.001) was observed. CONCLUSIONS Improvement in the severity of preexisting TD was achieved with olanzapine and persisted throughout the 8-month study and during each dose reduction period. Overall improvement in clinical status suggests that olanzapine may be effective for the long-term management of schizophrenia patients with preexisting TD.
Collapse
Affiliation(s)
- Bruce J Kinon
- Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 4133, Indianapolis, IN 46285, USA.
| | | | | | | | | |
Collapse
|
|
37
|
Garcia-Unzueta MT, Herran A, Sierra-Biddle D, Amado JA, Vázquez-Barquero JL, Alvarez C. Alterations of liver function test in patients treated with antipsychotics. J Clin Lab Anal 2003; 17:216-8. [PMID: 14614743 PMCID: PMC6807977 DOI: 10.1002/jcla.10094] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2002] [Accepted: 04/03/2003] [Indexed: 11/06/2022] Open
Abstract
The prevalence of alterations of liver function tests in patients treated with a wide range of antypsychotics is unknown. The aim of this study was to analyze the effects of antipsychotics on liver function tests in a population of schizophrenic outpatients. Concentrations of AST, ALT, GGT, alkaline phosphatase, albumin, and bilirubin were determined in 54 patients fitting DSM-IV criteria of schizophrenia, and the same number of sex- and age-matched healthy subjects. Assessments included the Clinical Global Impression (CGI) and the Positive and Negative Syndrome Scale (PANSS) in addition to treatment related variables. Transaminases concentrations were slightly elevated in study patients compared to healthy controls, but without statistical significance. Alkaline phosphatase showed higher values in schizophrenic patients. Albumin and bilirubin were lower in study patients. Liver function tests abnormalities were found in about 10% of schizophrenic patients treated with antipsychotics. Treatment with depot phenotiazines induces alteration in these tests more frequently than treatment with other antipsychotics. PANSS negative subscale scores directly correlated with alkaline phosphatase and inversely correlated with albumin. A substantial number of patients in treatment with antipsychotic drugs present alterations of liver function tests. Both pharmacological and clinical factors could be related with these alterations.
Collapse
Affiliation(s)
- M Teresa Garcia-Unzueta
- Department of Endocrinology, University Hospital "Marqués de Valdecilla," University of Cantabria, Santander, Spain.
| | | | | | | | | | | |
Collapse
|
|
38
|
Abstract
OBJECTIVE To describe patterns of self-reported medication use in a population-based sample of people with psychotic disorders; to establish correlates with clinical variables; to determine perceived side-effect burden; and investigate patient perception of efficacy for different classes of antipsychotic agent. METHODS Using the Australian Low Prevalence (Psychosis) Study database we analysed patterns of psychotropic medication and examined their clinical correlates. We also determined rates of reported side-effects and perceived benefit or otherwise associated with the different antipsychotic drugs. RESULTS Of the 1126 persons interviewed, 88.6% were on psychotropic medication; 54.3% were using "typical" antipsychotics (24.8% in depot form), while 8.3% were on clozapine, 13.3% on risperidone, and 8.8% on olanzapine. Around 30% of women, and 20% of men, were on mood stabilizers or antidepressants. Over half of respondents were on more than one agent. Of those on only one agent, nearly 80% reported at least one side-effect; the mean number of side-effects was 3.9 for typical antipsychotics, and 3.3 for atypicals. Atypicals, notably clozapine, tended to be rated by patients as more efficacious than typicals; depot preparations, in particular, tended to be seen as unhelpful, and were associated with a higher side-effect burden. CONCLUSIONS This study presents an insight into patients' perception of efficacy and side-effects of antipsychotic medications. The findings have implications for clinicians, and can inform treatment options in people with psychotic disorders.
Collapse
Affiliation(s)
- David Castle
- Department of Psychiatry and Behavioural Science, University of Western Australia, 16 The Terrace, Fremantle 6160, Australia
| | | | | |
Collapse
|
|
39
|
Abstract
The example of schizophrenia is used to illustrate how sex hormones affect the presentation of illness and its treatment. Organization and activation effects of hormones are explained, and behavior is shown to result from a complex interplay of hormones, brain mechanisms, and social pressures. Sex differences in schizophrenia (in onset age, symptoms, antipsychotic, and other treatment) are consequences of this interplay and impact on the clinician's ability to diagnose, treat, prognosticate, and prevent the disability and distress of schizophrenia.
Collapse
Affiliation(s)
- Mary V Seeman
- Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada.
| |
Collapse
|
|
40
|
Waraich PS, Adams CE, Roque M, Hamill KM, Marti J. Haloperidol dose for the acute phase of schizophrenia. Cochrane Database Syst Rev 2002:CD001951. [PMID: 12137638 DOI: 10.1002/14651858.cd001951] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND Haloperidol is a benchmark, accessible antipsychotic against which the effects of newer treatments are gauged. OBJECTIVES The primary goal of this review is to determine the best range of doses for haloperidol for the treatment of people acutely ill with schizophrenia. SEARCH STRATEGY The reviewers searched Biological Abstracts (1980-1999), CINAHL (1982-1999), The Cochrane Library (1999, Issue 2), The Cochrane Schizophrenia Group's Register (December 1999), EMBASE (1980-1999), MEDLINE (1966-1999) and PsycLIT (1887-1999). They also inspected all references of all identified trials and included studies sought as a citation on SCISEARCH database (1980-1999). Authors of identified studies and pharmaceutical companies were also contacted. SELECTION CRITERIA Studies were selected if they involved people being treated for acute schizophrenia, randomised to two or more dose ranges of non-depot haloperidol, and if they reported clinically meaningful outcomes. DATA COLLECTION AND ANALYSIS The reviewers independently and blindly inspected citations (10% reliability check), they ordered papers, and reliably re-inspected and quality assessed the full reports. The reviewers, again working independently, also extracted data. For homogeneous dichotomous data the relative risk (RR), 95% confidence intervals (CI) were calculated on an intention-to-treat basis. Reviewers assumed that people who left the study early or were lost to follow-up had a negative outcome. Weighted mean differences (WMD) were calculated for continuous outcomes that reported intention to treat (ITT), last observation carried forward (LOCF) data. Data was excluded if loss to follow-up was greater than 50%. MAIN RESULTS Sixteen trials with nineteen different randomised dose comparisons were included. No studies reported data on relapse rates, quality of life and none compared >1.5-3.0 mg/day haloperidol to higher dose ranges. Using low doses (>3-7.5mg/day) did not clearly result in loss of efficacy (no clinically important improvement in global state, versus >7.5-15mg/day n=48, 1 RCT, RR 1.09 CI 0.7 to 1.8; versus >15-35mg/day n=81, 2 RCTs, 0.95 CI 0.8 to 1.2). Doses of haloperidol in the range of >3-7.5 mg/day had a lower rate of development of clinically significant extrapyramidal adverse effects than higher doses (clinically significant extrapyramidal adverse effects, versus >7.5-15mg/day n=64, 2 RCTs, RR 0.12 CI 0.01 to 2.1; versus >15-35mg/day n=144, 3 RCTs RR 0.59 CI 0.5 to 0.8, NNH 3 CI 2 to 6; versus >35mg/day n=86, 2 RCTs, RR 0.70 CI 0.5 to 1.1). All other comparisons between dose ranges did not yield statistically significant differences, but several, particularly with lower dose ranges, were underpowered to detect clinically meaningful differences. REVIEWER'S CONCLUSIONS No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.
Collapse
Affiliation(s)
- P S Waraich
- Department of Psychiatry, University of British Columbia, 1081 Burrard St., Rm 306, Comox Building, Vancouver, British Columbia, Canada, V6Z 1Y6.
| | | | | | | | | |
Collapse
|
|
41
|
|
|
42
|
Delieu JM, Badawoud M, Williams MA, Horobin RW, Duguid JK. Antipsychotic drugs result in the formation of immature neutrophil leucocytes in schizophrenic patients. J Psychopharmacol 2001; 15:191-4. [PMID: 11565627 DOI: 10.1177/026988110101500306] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Subclinical abnormality of neutrophil populations of patients suffering from schizophrenia and medicated with antipsychotic drugs was evaluated using cellular immaturity as a criterion. Neutrophil maturity of patients and controls was compared by determining mean nuclear lobularity in peripheral blood smears. White blood cell and neutrophil counts were made. Subjects were patients medicated with chlorpromazine (n = 17) or clozapine (n = 48). Controls (n = 58) were healthy, non-medicated clinical and academic staff. Determination of mean lobe number involved assessment of 300 neutrophils per individual. For subject and control groups, means and medians of mean lobe numbers and mean white cell and neutrophil counts were determined. Means for each group were compared using the Mann-Whitney U-test; variances using F ratios. Means of lobe numbers of both patient populations were significantly different (p < 0.0001) compared to controls. Two-thirds of patients had mean lobe numbers outside the control range. Dose-response (mean lobe number) plots were significant for patients medicated with both chlorpromazine and clozapine. White cell and neutrophil counts in patients and controls did not differ significantly. For six patients, mean lobe numbers were obtained before and after medication commenced and all showed lowering of mean lobe number. The mean lobe number of the one patient who subsequently suffered from agranulocytosis was at the low end of the patient range. Thus, patients medicated with antipsychotic drugs typically have immature neutrophils, but normal white cell and neutrophil numbers. This effect is probably drug-induced. Mean lobe number may predict patients at risk from agranulocytosis.
Collapse
Affiliation(s)
- J M Delieu
- University College of Wales, Bangor, Faculty of Health Studies, Archimedes Centre, Wrexham Technology Park, UK
| | | | | | | | | |
Collapse
|
|
43
|
Vinson DR, Migala AF, Quesenberry CP. Slow infusion for the prevention of akathisia induced by prochlorperazine: a randomized controlled trial. J Emerg Med 2001; 20:113-9. [PMID: 11207403 DOI: 10.1016/s0736-4679(00)00297-3] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The utility of intravenous prochlorperazine (PCZ) in the treatment of nausea, vomiting, and headache may be limited by the akathisia that occurs frequently with the recommended 2-min infusion rate. We tested the hypothesis that decreasing the rate of PCZ infusion to 15 min reduces the incidence of akathisia at 1 hour. This double-blinded, randomized, controlled trial was conducted in the Emergency Department of an academic tertiary-care medical center with an annual census of 95,000 emergency patient visits. We enrolled a convenience sample of adult patients who received 10 mg i.v. PCZ for the treatment of nausea, vomiting, or headache. Subjects were randomized to receive either a 2-min infusion of PCZ (10 mg) followed by a 15-min infusion of saline, or a 2-min infusion of saline followed by a 15-min infusion of prochlorperazine. The incidence of akathisia at 1 hour was measured by using explicit diagnostic criteria. One hundred sixty patients were randomly enrolled into two groups, which were comparable with respect to age, gender, weight, and complaint. Akathisia developed in 31 of 84 patients (36.9%) who received the 2-min infusion of PCZ and in 18 of 76 patients (23.7%) who received the 15-min infusion of PCZ (p = 0.07), a 36% (95% CI, -5% to 61%) relative reduction. The delta from pre-infusion to postinfusion scores between the two groups was not significant (p = 0.19). We conclude that slowing the rate of PCZ infusion does not decrease akathisia.
Collapse
Affiliation(s)
- D R Vinson
- Department of Emergency Medicine, The Permanente Medical Group, Kaiser Permanente Medical Center, 2025 Morse Ave., Sacramento, CA 95825, USA
| | | | | |
Collapse
|
|
44
|
Affiliation(s)
- S R Porter
- Department of Oral Medicine, Eastman Dental Institute for Oral Health Care Sciences, University College London, London, England, UK
| | | |
Collapse
|
|
45
|
Abstract
Gabapentin is a relatively new anticonvulsant indicated for adjunctive therapy in the treatment of partial seizures, with and without secondary generalization, in adults with epilepsy. Overall, it has a minimal side effect profile compared with other anticonvulsant agents. Postmarketing surveillance is needed to further delineate the spectrum of adverse events that may be experienced by patients treated with this medication. This is a case report of a 25-year-old man with a 10-year history of mood swings that progressively worsened and resulted in a suicide attempt 8 months before his first appointment. A diagnosis of bipolar disorder was established, and a clinical interview ruled out other mental disorders. The patient was administered gabapentin 300 mg/day, and the dose was titrated upward to 900 mg/day. A follow-up appointment revealed improved control of his bipolar symptoms. However, the patient reported that he could not have an orgasm during sexual intercourse. The medication was changed to valproic acid 250 mg three times daily. His bipolar symptoms remained under control and the anorgasmia resolved. This was maintained at the next follow-up appointment. The side effect profile and therapeutic monitoring requirements of gabapentin are favorable when compared with those of other anticonvulsant agents. However, because this agent is relatively new, especially for use in the treatment of bipolar disorder, a more thorough development of its side effect profile is needed. Observing, recording, and reporting atypical adverse events and side effects are critical to postmarketing surveillance and enhance the clinician's ability to make rational therapeutic decisions.
Collapse
Affiliation(s)
- G E Brannon
- Department of Psychiatry, Louisiana State University School of Medicine in Shreveport, 71130, USA
| | | |
Collapse
|
|
46
|
Abstract
A program for women with schizophrenia that combines inpatient, outpatient, and outreach services is described. The program was established at the Clarke Institute of Psychiatry at the University of Toronto in 1995. Services include a comprehensive patient and family assessment, with subsequent recommendations to the treating clinician about differential diagnosis, psychopharmacologic and psychosocial treatments, and patient management during pregnancy and early parenthood. Other components of the program are home-based outreach services, substance abuse counseling, instruction of new mothers and parenting training, sex education, relationship-focused groups, and self-protection in an urban environment to prevent victimization. The clinic has established liaisons with pediatricians and gynecologists in the community to provide care to clinic patients. Linkages have also been established with agencies and facilities to fill gaps in the service spectrum, such as fitness programs and leisure activities and children's aid and protection.
Collapse
Affiliation(s)
- M V Seeman
- Clarke Institute of Psychiatry at the University of Toronto, Ontario.
| | | |
Collapse
|