Risperidone for treatment-refractory major depressive disorder: a randomized trial.

BACKGROUND

Major depressive disorder has high prevalence, morbidity, and mortality. Inadequate results with antidepressants have prompts addition of a nonstandard treatment (augmentation therapy).

OBJECTIVE

To assess whether augmentation therapy with risperidone reduces symptoms and increases response to antidepressant therapy and remission of depression in adults.

DESIGN

Multicenter, double-blind, placebo-controlled, randomized trial conducted from 19 October 2004 to 17 November 2005.

SETTING

75 primary care and psychiatric centers.

PATIENTS

274 outpatient adults with major depressive disorder that was suboptimally responsive to antidepressant therapy.

INTERVENTION

After a 4-week run-in period to ensure insufficient response to standard antidepressants, patients were randomly assigned to receive risperidone, 1 mg/d, or placebo for 6 weeks. After 4 weeks, the dosage of risperidone was increased to 2 mg/d in some cases.

MEASUREMENTS

Symptoms were measured by using the 17-item Hamilton Rating Scale for Depression (HRSD-17). Other outcomes were response to therapy, remission of depression, and various clinician- and patient-rated assessments.

RESULTS

Of the intention-to-treat population (268 patients), 81% (111 of 137) who received risperidone and 87.8% (115 of 131) who received placebo completed 6 weeks of double-blind treatment. Mean (+/-SE) HRSD-17 scores improved more in the risperidone augmentation group than in the placebo group (13.4 +/- 0.54 vs. 16.2 +/- 0.53; difference, -2.8 +/- 0.72 [95% CI, -4.2 to -1.4]; P <0.001). More risperidone recipients than placebo recipients experienced remission of depression (24.5% [26 of 106] vs. 10.7% [12 of 112]; P = 0.004) and had a response (46.2% [49 of 106] vs. 29.5% [33 of 112]; P = 0.004). Headache (8.8% of risperidone recipients vs. 14.5% of placebo recipients), somnolence (5.1% vs. 1.5%), and dry mouth (5.1% vs. 0.8%) were the most frequently reported adverse events.

LIMITATIONS

Patients were receiving many different antidepressants, and the duration of augmentation therapy was limited.

CONCLUSION

Risperidone augmentation produced a statistically significant mean reduction in depression symptoms, substantially increased remission and response, and improved other patient- and clinician-rated measures. ClinicalTrials.gov registration number: NCT00095134.