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Antidepressant Augmentation with Atypicals
Papakostas G, Shelton R, Smith J, Fava M.
Posted: September 2007  
Journal of Clinical Psychiatry  2007;68:826-831

Atypical antipsychotics appear to be effective adjuncts to antidepressants for treatment-resistant depression, according to a meta-analysis.

Methods:   All randomized, placebo-controlled clinical trials of adjunctive atypical antipsychotics for acute treatment of resistant depression using either the Hamilton Rating Scale for Depression (HAM-D) or the Montgomery-Asberg Depression Rating Scale (MADRS) were identified. The trials included a total of 1500 patients who received adjunctive treatment with either placebo or with olanzapine, quetiapine, or risperidone. All studies reported a decrease in the HAM-D or MADRS score, but the definition of remission varied among trials.

Results:   Patients who received augmentation with an atypical antipsychotic were more likely to respond and to achieve remission than those receiving placebo. Pooled response rates were 57% with atypicals and 35% with placebo; remission rates were 47% with atypicals and 22% with placebo. Overall discontinuation rates did not differ between atypicals and placebo, but patients receiving an atypical were 3 times as likely to discontinue because of adverse events.

Discussion:   Data reports on off-label prescribing suggest that atypical antipsychotics are widely used to augment antidepressants. Although the meta-analysis supports this use, the comparative efficacy relative to othr augmenting drugs or to cognitive-behavioral therapy is unknown, and the results can not be generalized to aripiprazole or ziprasidone. Atypical antipsychotics carry a potentially significant side effect burden, and tardive dyskinesia remains a significant risk.