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.


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


METHODS
75 primary care and psychiatric centers.


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


METHODS
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.


METHODS
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.


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


CONCLUSIONS
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.
Mahmoud
Ramy A
RA
Ortho-McNeil Janssen Scientific Affairs, Titusville, New Jersey, USA. rmahmou@ethus.jnj.com
Pandina
Gahan J
GJ
Turkoz
Ibrahim
I
Kosik-Gonzalez
Colette
C
Canuso
Carla M
CM
Kujawa
Mary J
MJ
Gharabawi-Garibaldi
Georges M
GM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D012074:Remission Induction; D018967:Risperidone / Q000008:administration & dosage* / Q000009:adverse effects
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D018967:Risperidone