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Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults A Systematic Review and Meta-analysis

Auteur(s) :

Alicia Ruelaz Maher, MD Margaret Maglione, MPP Steven Bagley, MD Marika Suttorp, MS Jian-Hui Hu, MPP,Brett Ewing, MS Zhen Wang, MS Martha Timmer, MS David Sultzer, MD Paul G. Shekelle, MD, PhD

Résumé :


Atypicalantipsychoticmedicationsarecommonlyusedforoff-labelcondi- tions such as agitation in dementia, anxiety, and obsessive-compulsive disorder.


To perform a systematic review on the efficacy and safety of atypical an- tipsychotic medications for use in conditions lacking approval for labeling and mar- keting by the US Food and Drug Administration.

Data Sources and Study Selection

Relevant studies published in the English language were identified by searches of 6 databases (PubMed, EMBASE, CINAHL, Psy- cInfo, Cochrane DARE, and CENTRAL) from inception through May 2011. Controlled trials comparing an atypical antipsychotic medication (risperidone, olanzapine, queti- apine, aripiprazole, ziprasidone, asenapine, iloperidone, or paliperidone) with pla- cebo, another atypical antipsychotic medication, or other pharmacotherapy for adult off-label conditions were included. Observational studies with sample sizes of greater than 1000 patients were included to assess adverse events.

Data Extraction

Independent article review and study quality assessment by 2 in- vestigators.
DataSynthesis Of12228citationsidentified,162contributeddatatotheefficacy review. Among 14 placebo-controlled trials of elderly patients with dementia report- ing a total global outcome score that includes symptoms such as psychosis, mood al- terations, and aggression, small but statistically significant effects sizes ranging from 0.12 and 0.20 were observed for aripiprazole, olanzapine, and risperidone. For gen- eralized anxiety disorder, a pooled analysis of 3 trials showed that quetiapine was as- sociated with a 26% greater likelihood of a favorable response (defined as at least 50% improvement on the Hamilton Anxiety Scale) compared with placebo. For obsessive- compulsive disorder, risperidone was associated with a 3.9-fold greater likelihood of a favorable response (defined as a 25% improvement on the Yale-Brown Obsessive Com- pulsive Scale) compared with placebo. In elderly patients, adverse events included an increased risk of death (number needed to harm [NNH] = 87), stroke (NNH = 53 for risperidone), extrapyramidal symptoms (NNH=10 for olanzapine; NNH=20 for ris- peridone), and urinary tract symptoms (NNH range = 16-36). In nonelderly adults, ad- verse events included weight gain (particularly with olanzapine), fatigue, sedation, akathi- sia (for aripiprazole), and extrapyramidal symptoms.


Benefits and harms vary among atypical antipsychotic medications for off-label use. For global behavioral symptom scores associated with dementia in elderly patients, small but statistically significant benefits were observed for aripiprazole, olanza- pine, and risperidone. Quetiapine was associated with benefits in the treatment of gen- eralized anxiety disorder, and risperidone was associated with benefits in the treatment of obsessive-compulsive disorder; however, adverse events were common.

JAMA, September 28, 2011-Vol 306, No. 12 - Lien vers la source

Collège Méditerranéen de Psychiatrie