Antipsychotic-induced type 2 diabetes: evidence from a large health plan database

Case evidence suggests that some of the atypical antipsychotics may induce type 2 diabetes. The objective of this study was to evaluate the association of antipsychotic treatment with type 2 diabetes in a large health plan database. Claims data for patients with psychosis within a health plan of nearly 2 million members were analyzed using logistic regression. Frequencies of newly treated type 2 diabetes in patients untreated with antipsychotics and among patients treated with quetiapine, risperidone, olanzapine, and conventional antipsychotics were compared. Based on exposure measured in months of antipsychotic treatment, quetiapine and risperidone patients had estimated odds of receiving treatment for type 2 diabetes that were lower than those of patients untreated with antipsychotics (not statistically significant); patients treated with conventional antipsychotics had estimated odds that were virtually equivalent to those of patients untreated with antipsychotics; olanzapine alone had odds that were significantly greater than those of patients untreated with antipsychotics (P = 0.0247). Odds ratios based on 8 months of screening for pre-existing type 2 diabetes and assuming 12 months of antipsychotic treatment were: risperidone = 0.660 (95% CI 0.311-1.408); olanzapine = 1.426 (95% CI 1.046-1.955); quetiapine = 0.976 (95% CI 0.422-2.271); and conventional antipsychotics = 1.049 (95% CI 0.688-1.613). Case reports, prospective trials, and other retrospective studies have increasingly implicated olanzapine and clozapine as causing or exacerbating type 2 diabetes. Few have implicated risperidone while evidence on quetiapine has been limited. This study supports earlier findings on risperidone versus olanzapine and builds evidence on quetiapine. Additional studies are needed to evaluate the association of antipsychotic treatment with type 2 diabetes.     

The impact of atypical antipsychotic medications on long-term memory dysfunction in schizophrenia spectrum disorder: a quantitative review

This meta-analytic review examines the efficacy of antipsychotic medications in ameliorating schizophrenia-related long-term memory (LTM) impairments. Twenty-three studies were reviewed that compared schizophrenia spectrum patients treated (a) with atypical versus typical antipsychotic medications, or (b) with various atypical treatments. In 17 atypical versus typical trials aggregating 939 participants, superior overall (verbal and nonverbal) LTM was detected in patients assigned to atypical trials. However, this difference was small (effect size estimate (ES) 0.17; 95% Confidence Interval (CI) 0.04 to 0.31) and specific to certain atypical treatments. Relative to typical antipsychotic trials, LTM superiority was marginally significant for risperidone trials (ES 0.20; 95% CI -0.03 to 0.44) and significant for olanzapine trials (ES 0.29; 95% CI 0.08 to 0.49). In contrast, clozapine trials did not produce a LTM advantage over typical trials (ES -0.06; 95% CI -0.35 to 0.23). Due to the lack of available studies, the effect of quetiapine was indeterminate. Direct comparison between atypical trials revealed a similar effect pattern. A marginally significant superiority in overall LTM was detected for risperidone and olanzapine compared to clozapine (ES 0.28; 95% CI -0.04 to 0.59), which reached significance for verbal LTM (ES 0.36; 95% CI 0.04 to 0.67). Finally, the beneficial impact of antipsychotic medications emerged as a function of differences in the anticholinergic properties of the treatment arms being compared.     

南京地区34家医院2010-2012年抗精神障碍药利用分析

目的:了解近3年来南京地区抗精神障碍药应用情况及发展趋势,为该类药品的临床合理应用提供参考。方法:采用回顾性方法,对2010-2012年南京地区34家医院抗精神障碍药的主要品种、销售金额、用量等情况进行统计、分析。结果:3年来南京地区抗精神障碍药的销售金额逐年上升,非典型抗精神障碍药占主导地位,购药金额构成比分别为98.33%、99.17%、99.01%。从用药频度(DDDs)来看,非典型抗精神障碍药也占主导地位,所占的DDDs构成比分别为71.64%、76.19%、79.51%;经典抗精神障碍药所占DDDs的构成比分别为28.36%、23.81%、20.49%,呈逐年下降趋势。2012年DDDs列前3位的抗精神障碍药分别是利培酮、奥氮平和奎硫平。结论:该地区使用的主要抗精神病药已经由传统的经典抗精神障碍药转向以利培酮、奥氮平、奎硫平为主的非典型抗精神病药。妥善解决药品价格问题,能促进抗精神障碍药有效、方便、经济地使用。     

Antipsychotic augmentation of serotonergic antidepressants in treatment-resistant obsessive-compulsive disorder: a meta-analysis of the randomized controlled trials.

This study aimed to determine the effectiveness of antipsychotic augmentation of serotonergic antidepressants in the management of treatment-resistant obsessive compulsive disorder by carrying out a meta-analysis of all randomized controlled trials. Studies selected through a literature search conducted in March 2006. Ten trials comparing antipsychotic drugs versus placebo met inclusion criteria (haloperidol [n=1], risperidone [n=3], olanzapine [n=2], quetiapine [n=4]). A total of 157 patients were randomized to study drug and 148 were randomized to placebo. Response occurred more often among patients randomized to antipsychotic drugs. The weighted combined response rate ratio by random effects meta-analysis was 3.31 (95% CI 1.40-7.84). Significant between studies heterogeneity was partly explained by the definition of refractoriness, the type and dose of the drug used and the inclusion or exclusion of patients with tic disorders. The study supports the use of antipsychotic drugs as an augmentation strategy but more and larger trials are needed.     

Diabetes mellitus and antipsychotic treatment in the United Kingdom.

OBJECTIVE: Treatment-emergent diabetes has been reported during exposure to conventional and atypical antipsychotics. This retrospective cohort study explored the UK General Practice Research Database (GPRD) to determine hazard ratios of diabetes for patients prescribed antipsychotics. METHODS: A Cox proportional hazard regression model using age, gender, and obesity (BMI > 30 kg/m2) was used to determine the hazard ratio (HR) of diabetes development in conventional antipsychotic (N = 59,089), atypical antipsychotic (N = 9053), individual antipsychotic, and general patient population cohorts (N = 1,491,548). RESULTS: Compared with the general GPRD patient population, patients exposed to conventional or atypical antipsychotics had a higher risk of developing diabetes (atypical antipsychotic cohort: HR = 2.9, CI = 2.0-4.4; and conventional antipsychotic cohort: HR = 1.9, CI = 1.6-2.3). The risk of developing diabetes during thioridazine, risperidone, or olanzapine treatment was significantly higher compared with the general GPRD patient population. CONCLUSION: Consistent with other epidemiology studies, this study supports an increased risk of developing diabetes during treatment with antipsychotics.     

Exploring the association between atypical neuroleptic agents and diabetes mellitus in older adults

STUDY OBJECTIVE: To explore the suggested association between atypical neuroleptic use and the development of diabetes mellitus, with a focus on older adults. DESIGN: Retrospective cohort study. SUBJECTS: Eleven thousand one hundred four older (> 65 yrs) residents of long-term care institutions in Ontario, Canada, who received either atypical neuroleptic agents, typical neuroleptic agents, benzodiazepines, or corticosteroids. MEASUREMENTS AND MAIN RESULTS: Each subject was followed for the development of a diabetic event, defined as newly prescribed antidiabetic drug therapy. Our Cox regression model was adjusted for age, sex, socioeconomic status, comorbidity, and concomitant use of beta-blockers, thiazide diuretics, and antiepileptic agents. The adjusted hazard ratio for the development of diabetes in patients receiving atypical neuroleptics compared with those receiving benzodiazepines (control group) was 0.89 (95% confidence interval [CI] 0.66-1.21). The adjusted hazard ratio for typical neuroleptic users compared with the benzodiazepine group was 1.27 (95% CI 0.91-1.77). As expected, patients receiving corticosteroid therapy were almost twice as likely to develop diabetes as those receiving benzodiazepines (adjusted hazard ratio 2.2, 95% CI 1.41-3.12). For patients receiving atypical neuroleptic agents, no statistically significant difference in the percentage of diabetic events was found among individual agents (2.1% olanzapine, 1% quetiapine, 2.1% risperidone). CONCLUSION: Drug therapy with atypical neuroleptic agents in older adults did not increase their risk of developing diabetes mellitus.     

Antipsychotic drugs in bipolar disorder

Antipsychotic drugs are useful in the treatment of acute mania and as maintenance treatment. While both typical and atypical antipsychotic drugs are able to diminish manic symptoms, agitation and aggression in acute mania, the atypical antipsychotic drugs enjoy a number of advantages, including significantly less extrapyramidal symptoms, diminished risk of tardive dyskinesia, lack of increase in serum prolactin levels (with the exception of risperidone), improvement in cognition, and possible decrease in suicidality. Most of the atypical antipsychotic drugs have been found to be effective as an add-on treatment (with mood stabilizers and antidepressant drugs) and sometimes as monotherapy in treatment-resistant bipolar patients. Long-acting typical neuroleptic drugs may be useful in the treatment of non-compliant bipolar patients. A small number of patients with schizophrenia treated with risperidone, olanzapine, or quetiapine experience a first episode of hypomania or mania. It is not apparent if this is a true drug-induced event or coincidental. Side-effects of note with the atypical antipsychotic drugs are weight gain (most prominently with olanzapine and clozapine), sedation, and agranulocytosis (clozapine). Atypical antipsychotic drugs are recommended for use in bipolar disorder for acute treatment, maintenance treatment, and for treatment-resistant patients.     

Incidence of diabetes in a general practice population: a database cohort study on the relationship with haloperidol, olanzapine, risperidone or quetiapine exposure

The present study aimed to estimate the incidence of diabetes in general practice patients who were treated with haloperidol, olanzapine, risperidone or quetiapine monotherapy and in subjects who were not exposed to antipsychotics. The design was a retrospective, up to 2 years, cohort study, with age-, sex- and length of observation-matching between subjects who were exposed and not exposed to antipsychotic drugs. Data were taken from the Health Search database, which contains information from 550 Italian general practitioners. Participants comprised 2,071 subjects taking haloperidol, 266 taking olanzapine, 567 taking risperidone and 109 taking quetiapine, in addition to 6,026 age- and sex-matched subjects who were not using antipsychotic drugs during the period of observation. Inclusion was limited to initially non-diabetic and antipsychotic drug-free individuals. The main outcome measure was the incidence of drug-treated diabetes. After age and sex correction by Cox regression analysis, the four groups treated with antipsychotics significantly differed from untreated subjects in hazard ratios for diabetes. The ratios for the haloperidol, olanzapine, risperidone and quetiapine groups were 12.4 (95% confidence interval 6.3-24.5), 20.4 (6.9-60.3), 18.7 (8.2-42.8) and 33.7 (9.2-123.6), respectively, with no significant differences when compared to each other.     

Time to discontinuation and self-discontinuation of olanzapine and risperidone in patients with schizophrenia in a naturalistic outpatient setting

BACKGROUND: Although efficacy of antipsychotic medications is well documented, their effectiveness in real-world practice is less robust. We examined the effectiveness of olanzapine and risperidone in schizophrenia in a naturalistic setting. METHODS: We used an electronic medical records database at a Veterans Affairs Medical Center to conduct a retrospective study of all new outpatient medication trials of olanzapine (n = 221) and risperidone (n = 274) over a 2-year period beginning January 1999 in patients diagnosed with schizophrenia or schizoaffective disorder. We defined medication discontinuation as a switch between the 2 agents (most switches) or self-discontinuation when a patient is without medication supply for longer than 1 month. RESULTS: Sample mean age (+/-SD) was 48.4 (+/-11.6) years; 91% were men. Discontinuation rates were high (73%), trending lower in olanzapine (70%) than risperidone (76%) (P = 0.12). Median time to discontinuation was 120 days (95% confidence interval [CI], 105-135), longer for olanzapine (150 days; 95% CI, 120-180) than risperidone (90 days; 95% CI, 71-109) (P = 0.04). Self-discontinuation was high (48%), with no significant difference between olanzapine (50%) and risperidone (46%). Switching rate was 25% and more likely to occur in risperidone (30%) than olanzapine (20%) (odds ratio, 1.72; 95% CI, 1.13-2.61). CONCLUSIONS: Effectiveness of antipsychotic medications in schizophrenia may be hampered by high rates of medication self-discontinuation in outpatient practice settings. Time to discontinuation suggests that olanzapine may be more effective than risperidone. Strategies to address causes of poor adherence should be incorporated in medication algorithms to optimize their effectiveness.     

Pharmacological management of atypical antipsychotic-induced weight gain

Excessive bodyweight gain was reported during the 1950s as an adverse effect of typical antipsychotic drug treatment, but the magnitude of bodyweight gain was found to be higher with the atypical antipsychotic drugs that were introduced after 1990. Clozapine and olanzapine produce the greatest bodyweight gain, ziprasidone and aripiprazole have a neutral influence, and quetiapine and risperidone cause an intermediate effect. In the CATIE study, the percentage of patients with bodyweight gain of >7% compared with baseline differed significantly between the antipsychotic drugs, i.e. 30%, 16%, 14%, 12% and 7% for olanzapine, quetiapine, risperidone, perphenazine (a typical antipsychotic) and ziprasidone, respectively (p<0.001). Appetite stimulation is probably a key cause of bodyweight gain, but genetic polymorphisms modify the bodyweight response during treatment with atypical antipsychotics. In addition to nutritional advice, programmed physical activity, cognitive-behavioural training and atypical antipsychotic switching, pharmacological adjunctive treatments have been assessed to counteract excessive bodyweight gain. In some clinical trials, nizatidine, amantadine, reboxetine, topiramate, sibutramine and metformin proved effective in preventing or reversing atypical antipsychotic-induced bodyweight gain; however, the results are inconclusive since few randomized, placebo-controlled clinical trials have been conducted. Indeed, most studies were short-term trials without adequate statistical power and, in the case of metformin, nizatidine and sibutramine, the results are contradictory. The tolerability profile of these agents is adequate. More studies are needed before formal recommendations on the use of these drugs can be made. Meanwhile, clinicians are advised to use any of these adjunctive treatments according to their individual pharmacological and tolerability profiles, and the patient's personal and family history of bodyweight gain and metabolic dysfunction.     

658例门诊精神病患者抗精神病药物应用分析

目的了解门诊精神病患者抗精神病药物的使用情况，为临床合理用药提供参考。方法抽样调查浙江省立同德医院2005年9月658张抗精神病药物处方用药情况。结果共涉及25种治疗方案，其中使用1种抗精神病药物的治疗方案有7种348张（52．89％），使用2种的有15种307张（46．66％），使用3种的有3种3张（0．45％）。抗精神病药物治疗方案居前5位的依次为利培酮、氯氮平、奥氮平、氯氮平＋碳酸锂、奎硫平；使用率居前5位的分别是氯氮平（35．41％）、利培酮（25．68％）、舒必利（19．76％）、奥氮平（13．83％）、奎硫平（13．37％）。结论该院抗精神病药物的处方用药情况基本合理，非典型抗精神病药物已成为临床首选。     

Glucose intolerance with atypical antipsychotics.

BACKGROUND: Previous studies have suggested that the atypical antipsychotics clozapine and olanzapine may be associated with an increased risk of glucose intolerance and diabetes mellitus. Early studies have also suggested an association between use of conventional antipsychotics and the development of glucose intolerance. OBJECTIVE: To examine quantitatively the association between glucose intolerance including diabetes mellitus and the use of the atypical antipsychotics clozapine, olanzapine or risperidone, and to identify possible risk factors for the development of glucose intolerance during treatment with these drugs. METHODS: All reports suggestive of glucose intolerance for clozapine, olanzapine and risperidone were identified in the WHO database for adverse drug reactions. In the analyses of possible risk factors for glucose intolerance all other reports of adverse drug reactions for clozapine, olanzapine and risperidone were used as reference. Using the Bayesian Confidence Propagation Neural Network method, the strengths of the associations over time between glucose intolerance and the use of these drugs were analysed. For comparison, the strengths of the associations between glucose intolerance and the use of the conventional antipsychotics haloperidol and chlorpromazine were also analysed. RESULTS: Clozapine, olanzapine and risperidone were significantly associated with glucose intolerance. In contrast, chlorpromazine and haloperidol were not associated with glucose intolerance. For clozapine, olanzapine and risperidone grouped together, the following potential risk factors for glucose intolerance were identified: an underlying diabetic condition (odds ratio [OR] 10.22, 95% CI 8.20-12.73), an increase in weight (OR 2.36, 95% CI 1.76-3.17), male gender (OR 1.27, 95% CI 1.11-1.47), and concomitant use of valproic acid (OR 1.97, 95% CI 1.61-2.40), selective serotonin reuptake inhibitors (OR 1.63, 95% CI 1.33-1.99) or buspirone (OR 2.24, 95% CI 1.33-3.77). CONCLUSION: Treatment with clozapine, olanzapine or risperidone appears to be associated with an increased risk of glucose intolerance.     

2014~2016年南京地区抗精神病药使用分析

分析南京地区抗精神病药的使用情况,为该类药物的合理使用提供参考。运用药物经济学的金额分析法和用药频度（DDDs）分析法对南京地区34家医院抗精神病药的销售金额、用药频度（DDDs）、日均费用（DDC）等数据进行统计分析。南京地区34家医院抗精神病药总的销售金额与用药频度（DDDs）逐年上升,非典型抗精神病药销售金额与用药频度（DDDs）的年平均增长率分别为8.17%和8.68%,典型抗精神病药销售金额与用药频度（DDDs）的年平均增长率分别为-4.63%和-9.98%。南京地区使用的抗精神病药是以奥氮平、阿立哌唑、利培酮、喹硫平为主的非典型抗精神病药,建议相关部门调整非典型抗精神病药价格及医保政策,惠及更多患者。