Use of risperidone as augmentation treatment for major depressive disorder.

Objective: To review the efficacy and safety of risperidone for augmentation treatment in patients with major depressive disorder who fail to achieve adequate response to antidepressant monotherapy.

Data Sources: A search of MEDLINE (1966-August 2010) and EMBASE (1980-August 2010) was conducted, using the terms risperidone and major depressive disorder. In addition, a manual search of the references cited in each publication identified from the database search was conducted to identify relevant articles.

Study Selection And Data Extraction: All English-language, peer-reviewed publications identified from the data sources were evaluated. Four clinical trials and 1 subanalysis of a clinical trial were included for analysis.

Data Synthesis: Risperidone is an atypical antipsychotic that displays antidepressant properties due to its activity at various serotonergic and dopaminergic receptors. Studies have demonstrated that risperidone augmentation may be effective and safe when used at low doses. Although several of the studies identified had limited sample sizes, all studies demonstrated improvement on various standardized depressive symptom assessment scales. Study durations ranged from 4 to 24 weeks, with doses ranging from 0.25 to 2 mg/day. The most common adverse effects associated with risperidone therapy were headache, dry mouth, and increased appetite.

Conclusions: Clinical evidence suggests that the use of risperidone as adjunctive therapy for treatment-resistant depression may improve rates of response and remission, but long-term effectiveness and safety cannot be determined at this time. Therefore, an adequate trial of first-line agents from different classes and/or a combination of agents from different classes would be recommended prior to initiation of risperidone. If the decision is made to start risperidone, health-care providers should ensure that patients are educated regarding the potential benefits and adverse effects before initiating risperidone.