Antipsychotic augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomized, placebo-controlled trials

Abstract

Because of the high number of patients with obsessive-compulsive disorder (OCD) not responding satisfactorily to initial monotherapy with serotonin reuptake inhibitors (SRIs), the evaluation of additional treatment options is highly relevant. To examine efficacy of add-on pharmacotherapy with antipsychotics, a systematic literature search was applied to identify all double-blind, randomized, placebo-controlled trials (DB-PC-RCTs) determining the efficacy of antipsychotic augmentation of SRIs in treatment-resistant OCD. The primary outcome of the pooled meta-analytic data analysis was response to the adjunctive antipsychotic treatment measured by both the rates of participants achieving response [defined as ≥ 35% reduction in Yale-Brown Obsessive-Compulsive Scale (YBOCS)] and mean changes in YBOCS total score. Twelve DB-PC-RCTs investigating quetiapine (N = 5), risperidone (N = 3), olanzapine (N = 2), aripiprazole (N = 1) and haloperidol (N = 1) with a total of 394 subjects were included. Significantly more patients responded to augmentation with antipsychotics than with placebo [relative risk = 2.10, 95% confidence intervals (CI) 1.16-3.80]. Additionally, the mean reduction of the YBOCS total score revealed an efficacy in favour of the antipsychotic medication [standardized mean difference (SMD) = 0.54, 95% CI 0.15-0.93]. Significant efficacy was identifiable only for risperidone, but not for quetiapine and olanzapine. The results regarding aripiprazole and haloperidol were inconsistent. Overall, about one-third of SRI-resistant OCD patients benefited from an augmentation strategy with antipsychotics. Based on the favourable risk:benefit ratio, risperidone can be considered as the agent of first choice and should be preferred to quetiapine and olanzapine. Further trials, mainly with higher antipsychotic doses, are required to optimize pharmacological treatment recommendations for SRI-refractory OCD.

Why have early investigational therapies of obsessive–compulsive disorder failed to materialise?

“…No firm conclusion can yet be drawn on other newer antipsychotics, because the available evidence is scant [16]. The same applies to rTMS and DBS.…”

Evidence-Based Treatments in Treatment-Naïve and Treatment-Resistant Pediatric Obsessive-Compulsive Disorder

“…Augmentation is the procedure off adding drugs with different mechanisms of action compared with the first-line SSRI in order to aid the therapeutic effects. Research indicates that in addition to serotonin, other neurotransmitters may be involved in the pathophysiology of OCD such as glutamate [10] and dopamine [11]. However, the evidence-based literature-at least for pediatric OCD-is lacking.…”

“…These work mainly by blocking the dopamine pathways within the cortex. In adults with OCD, randomized controlled trials (RCTs) have been conducted to show the effects of risperidone (e.g., [60]), aripiprazole, quetiapine, olanzapine, and haloperidol, which is a typical or first generation antipsychotic [11,61]. The effect seems to be greater in patients with comorbid OCD and tic disorder [61].…”

“…We also filtered in the terms of Brandomized controlled trials^and Bmeta-analysis^. In addition, we read recent reviews and expert guidelines to find any relevant additional publications [1,[4][5][6][7][8][9][10][11].…”

Sintomas obsessivo-compulsivos em escolares: prevalência, dimensões psicopatológicas, agregação familiar, comorbidades e fatores clínicos associados

“…Several clinical trials in adults proposed a significant efficacy for haloperidol and atypical antipsychotics in adults (92), mainly risperidone (127), quetiapine (128), aripiprazol (124), and olanzapine (129).…”