A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression

Abstract

Objective-Patients (30-50%) with non-psychotic major depression will not respond despite an adequate trial of antidepressant medication. This study evaluated risperidone as an augmenting agent for patients who failed or only partially responded to an adequate trial of an antidepressant medication.Method-Ninety-seven patients with unipolar non-psychotic major depression who were not responsive to antidepressant monotherapy were randomized to risperidone (0.5-3 mg/day) or placebo augmentation in a four-week, double-blind, placebo controlled treatment trial. The primary outcome measure was remission defined by a score of ≤10 on the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes measures were the Hamilton Rating Scale for Depression, the Clinician Global Impression of Severity scale and the overall satisfaction item of the Quality of Life and Enjoyment Questionnaire.Results-Subjects in both treatment groups improved significantly over time. The odds of remitting were significantly better for patients in the risperidone vs. placebo arm (OR = 3.33, p = . 011). At the end of 4 weeks of treatment 52% of the risperidone augmentation group remitted (MADRS ≤ 10) compared to 24% of the placebo augmentation group (CMH(1) = 6.48, p = .011), but the two groups were converging. Patients in the risperidone group also reported significantly more improvement in quality-of-life than patients in the placebo group. There were no betweengroup differences in the number of adverse events reported, however, weight gain was significantly higher in the group receiving risperidone. Conclusion-Augmentation of an antidepressant with risperidone for patients with difficult-totreat depression leads to more rapid response and a higher remission rate and better quality-of-life.

Augmentation Treatments with Second-generation Antipsychotics to Antidepressants in Treatment-resistant Depression

“…Thase et al [18] includes two trials (study 1 and study 2). Response was defined as an improvement of C50% from baseline to endpoint on the HAM-D or the MADRS, and remission was defined as a MADRS total score of B10 and C50% reduction in MADRS total score in the trials except trials by Shelton et al [15] and Corya et al [17] (two subsequent MADRS total score B8), McIntyre and Gendron [22] and Mahmoud et al [24] (HAM-D-17 score B7), Bauer et al [20], El-Khalili et al [21] and Keitner et al [26] (MADRS total score B8), trial by Reeves et al [25] aripiprazole than receiving placebo (0.6 %) had a weight gain of 7 % or more [13]. The difference in weight gain with SGA adjunctive therapy was small, and no other adverse event related to metabolic function, such as changes in mean waist circumference, total cholesterol, high or low-density lipoprotein cholesterol, triglycerides, fasting plasma glucose, or haemoglobin A1C, was associated with aripiprazole augmentation in short-term trials.…”

“…Three double-blind RCTs [24][25][26] investigated the effects of risperidone augmentation in conjunction with various antidepressant therapies in patients with TRD (Table 2). In those trials, risperidone was initiated at 0.25-1 mg/day, and the dose was titrated to a maximum of either 2 or 3 mg/day, with a mean dose of 1-2 mg/day at the end of the studies.…”

“…Furthermore, the mean MADRS score change at study endpoint was not statistically significant between the risperidone (-22.1) and placebo group (-14.4). Keitner et al [26] investigated the remission rate, assessed by MADRS, and found a significantly higher rate for the risperidone group (51.6 %) compared with the placebo group (24.2 %) after 4 weeks in subjects with TRD (n = 95). Two studies (n = 241 and n = 63) evaluated the sustained effect of risperidone over a 6-month period [27,28].…”

“…1). The data were extracted from nine studies that had all data for the rate of remission, discontinuation due to adverse events and most common adverse effects in each SGA [7,9,19,[22][23][24][25][26]. As for treatment efficacy, the NNT was six for risperidone, eight for aripiprazole, nine for quetiapine and 13 for olanzapine.…”

“…1 The number needed to treat (remission rate) and number needed to harm (rates of discontinuation due to adverse events and most common side effects) of each drug (%). Pooled data from controlled trials of olanzapine [19], risperidone [24][25][26], quetiapine [20,22], aripiprazole [7][8][9]. The Cochran data [6] and data in a metaanalysis [5] were referred.…”