Atypical antipsychotic agents are another alternative
A 2007 meta-analysis of 10 clinical trials involving 1500 outpatients studied the efficacy of augmenting standard antidepressants with atypical antipsychotic agents to treat resistant major depressive disorder.6 Across the trials, the pooled risk ratio (RR) for remission was 1.75 (95% CI, 1.36-2.24) and for response rates was 1.35 (95% CI, 1.13-1.63). Pooled rates for remission and response were 47.4% vs 22.3% (NNT=4) and 57.2% vs 35.4% (NNT=4.6), respectively.
Although the meta-analysis found no difference in overall discontinuation rates (P=.929), the rate of discontinuation because of adverse events was lower among placebo-treated patients (RR=3.38, P<.0001). These results suggest a role for atypical antipsychotic agents in augmenting standard antidepressants for treatment-resistant major depressive disorder.
Recommendations
Both the American Psychiatric Association7 and the Institute for Clinical Systems Improvement8 recommend considering a trial of lithium or thyroid augmentation for patients who respond only partially to initial antidepressant therapy. Many experienced clinicians consider lithium to be the most effective adjunct. The APA cautions, however, that its Major Depressive Disorder Practice Guideline, published in 2000, is no longer current.9 An update is expected by the end of the year.
Other options include maximizing the initial treatment, switching to another agent, or augmenting initial treatment with another antidepressant agent or psychotherapy. Before prescribing any additional treatments for patients who fail to respond to initial antidepressant therapy, however, primary care physicians need to be mindful of the fact that empirical data regarding the relative effectiveness of these strategies are limited—and that they should consider whether the patients they’re treating have bipolar—rather than unipolar—depression.