What role do atypical antipsychotic drugs have in treatment-resistant depression?

Despite significant advances in the treatment of depression, many patients fail to respond to treatment with adequate dose and duration. Multiple therapeutic approaches are available for the treatment of patients not responding to standard antidepressant medication. These include switching medication or combination and augmentation strategies. A substantial number of patients do not respond to multiple treatment trials. These patients suffer from treatment-resistant depression (TRD) and represent a challenge to the treating physician. There have been a growing number of reports on the use of atypical antipsychotics as augmenting agents in nonpsychotic TRD. Second-generation antipsychotics are less likely to provoke parkinsonian side effects. It has also been reported that these agents produce lower rates of tardive movement disorders than traditional neuroleptics. Furthermore, second-generation antipsychotics are serotonin-2A/2C antagonists, possibly allowing them to improve the efficacy and some aspects of the side effect profile of selective serotonin reuptake inhibitors (SSRIs). Weight gain and sedation are likely to be the most common adverse events of such combined therapy. In a recent controlled clinical trial, the atypical antipsychotic olanzapine was combined with fluoxetine therapy in an 8-week, double-blind clinical trial in patients with TRD. This combination drug therapy demonstrated clinical efficacy on several rating scales and showed rapid onset of action. Although more studies will be required to confirm and extend these findings, the results suggest that there may be a clinical benefit to combining atypical antipsychotics with SSRIs in nonpsychotic TRD.