Objectives: Antipsychotic medications are approved by the U.S. Food and Drug Administration (FDA) for treatment of schizophrenia, bipolar disorder, and for some drugs, depression. We performed a systematic review on the efficacy and safety of atypical antipsychotic drugs for use in conditions lacking FDA approval.
Data Sources: We searched PubMed, Embase, PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane DARE (Database of Abstracts of Reviews of Effects), and Cochrane CENTRAL (Cochrane Central Register of Controlled Trials) from inception to May 2011. We included only English-language studies.
Review Methods: Controlled trials comparing an atypical antipsychotic (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine, iloperidone, paliperidone) to either placebo, another atypical antipsychotic drug, or other pharmacotherapy, for the off-label conditions of anxiety disorder, attention deficit hyperactivity disorder, dementia and severe geriatric agitation, major depressive disorder, eating disorders, insomnia, obsessive compulsive disorder (OCD), post traumatic stress disorder (PTSD), personality disorders, substance abuse, and Tourette’s syndrome were included. Observational studies with sample sizes greater than 1,000 were included to assess rare adverse events. Two investigators conducted independent article review, data abstraction, and study quality assessment.
Results: One hundred seventy trials contributed data to the efficacy review. Among the placebo-controlled trials of elderly patients with dementia reporting a total/global outcome score that includes symptoms such as psychosis, mood alterations, and aggression, small but statistically significant effect sizes ranging from 0.12 and 0.20 were observed for aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder, pooled analysis of three large trials showed that quetiapine was associated with a 26 percent greater likelihood of “responding,” defined as at least 50 percent improvement on the Hamilton Anxiety Scale, compared with placebo. For obsessive-compulsive disorder, risperidone was associated with a 3.9-fold greater likelihood of “responding,” defined as a 25 to 35 percent improvement on the Yale Brown Obsessive Compulsive Scale (YBOCS) compared with placebo. We identified 6 trials on eating disorders, 12 on personality disorder, an existing meta-analysis and 10 trials of risperidone or olanzapine for PTSD, 36 trials for depression of which 7 assessed drugs without an FDA-approved indication, and 33 trials of aripiprazole, olanzapine, quetiapine, or risperidone for treating substance abuse disorders. We identified one small trial (N=13) of atypical antipsychotics for insomnia which was inconclusive. For eating disorder patients specifically, evidence shows that atypicals are do not cause significant weight gain. The level of evidence is mixed regarding personality disorders and moderate for an association of risperidone with improving post-traumatic stress disorder. Evidence does not support efficacy of atypical antipsychotics for substance abuse. In elderly patients, adverse events included an increased risk of death (number needed to harm [NNH]=87), stroke (for risperidone, NNH=53), extrapyramidal symptoms (for olanzapine (NNH=10) and risperidone (NNH=20), and urinary symptoms (NNH= from 16 to 36). In nonelderly adults, adverse events included weight gain (particularly with olanzapine), fatigue, sedation, akithisia (for aripiprazole) and extrapyramidal symptoms. Direct comparisons of different atypical antipsychotics for off-label conditions are rare.
Conclusions: Benefits and harms vary among atypical antipsychotics for off-label usage. For symptoms associated with dementia in elderly patients, small but statistically significant benefits were observed for aripiprazole, olanzapine, and risperidone. Quetiapine was associated with benefits in the treatment of generalized anxiety disorder, and risperidone was associated with benefits in the treatment of OCD; however, adverse events were common.
Summary of the Comparative Effectiveness Review on Off-Label Use of Atypical AntipsychoticsAR Maher et al. J Manag Care Pharm 18 (5 Suppl B), S1-20. PMID 22784311. - ReviewAntipsychotic medications are FDA approved for the treatment of schizophrenia and bipolar disorder. Conventional antipsychotics have been widely used for decades and spur …
Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults: A Systematic Review and Meta-AnalysisAR Maher et al. JAMA 306 (12), 1359-69. PMID 21954480. - ReviewBenefits and harms vary among atypical antipsychotic medications for off-label use. For global behavioral symptom scores associated with dementia in elderly patients, sma …
Drug Class Review: Atypical Antipsychotic Drugs: Final Update 3 Report [Internet]M McDonagh et al. PMID 21348048. - ReviewFew differences were seen among the atypical antipsychotics in short-term efficacy in patients with schizophrenia, bipolar disorder, or dementia. Differences in most effe …
An Open, Large, 6-month Naturalistic Study of Outcome in Schizophrenic Outpatients, Treated With OlanzapineM Krzystanek et al. Hum Psychopharmacol 26 (1), 81-5. PMID 23055416. - ReviewOlanzapine may be a somewhat more efficacious drug than some other second generation antipsychotic drugs. This small superiority in efficacy needs to be weighed against a …
Atypical Antipsychotics for Disruptive Behaviour Disorders in Children and YouthsJH Loy et al. Cochrane Database Syst Rev 8 (8), CD008559. PMID 28791693. - ReviewThere is some evidence that in the short term risperidone may reduce aggression and conduct problems in children and youths with disruptive behaviour disorders There is a …
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Influence of Risperidone on Balance Control in Young Healthy IndividualsP Corbeil et al. Psychopharmacology (Berl) 222 (1), 59-69. PMID 22234381. - Randomized Controlled TrialRisperidone administered at low doses did not elicit clinically detectable EPS but had significant effects on balance control. A dose-response effect on impairment of bal …