Pindolol augmentation of selective serotonin reuptake inhibitors and clomipramine for the treatment of obsessive-compulsive disorder: A meta-analysis

Obsessive-compulsive disorder (OCD) is associated with an estimated lifetime prevalence of 2%. An estimated 50–80% of the patients are treatment-resistant, with either no response or a limited response to adequate trials of selective serotonin reuptake inhibitors (SSRIs) and clomipramine. The American Psychiatric Association (APA) Practice Guidelines recommend augmentation with atypical antipsychotics, an alternate SSRI, mirtazapine, or venlafaxine as second-line treatment options. The use of pindolol is currently considered as a third-line augmentation strategy for patients with inadequate response to the aforementioned treatment options. Pindolol exerts antihypertensive effects through β-blockade, and is also a potent serotonin 5HT1A presynaptic receptor antagonist. The serotonin 5HT1A receptor is primarily an autoreceptor, and agonism of this receptor downregulates serotonin release. Pindolol augmentation theoretically leads to an increased release of serotonin through the blockade of the 5HT1A receptor. The APA guidelines note that limited evidence exists to support the use of pindolol as an augmentation strategy, and a meta-analytic review would aid in the evaluation of the current evidence for its use. A meta-analysis is particularly useful in situations where few studies have been performed, especially when those studies have employed small sample sizes. In these situations, a meta-analysis can provide an overall measure of medication efficacy that would be otherwise unavailable, owing to low statistical power. To date, no systematic review or meta-analysis of the literature examining the efficacy of pindolol augmentation has been performed. The purpose of this study was to determine the level of evidence supporting pindolol augmentation of SSRIs and clomipramine for the treatment of OCD, by performing a quantitative review of the literature through the use of meta-analytic techniques. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRIMSA) guidelines were followed. Ovid Medline, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and review of article references were used to search for all studies examining pindolol augmentation for the treatment of OCD. The search terms included pindolol, beta-blocker, serotonin 5HT1A, and obsessive-compulsive disorder. To maximize the statistical power, all studies that were published in peer-reviewed journals prior to June 30, 2014, were included, regardless of the study design or language of publication. The Yale–Brown Obsessive-Compulsive Scale is the most commonly used measure of OCD severity, and was used as the measure of efficacy in the meta-analysis. The standard meta-analytic techniques were employed for data extraction. Calculations were performed manually, with the use of the Statistical Package for Social Sciences, as a second point of reference. The Pearson correlation coefficient r was used as the effect size measure, given that it was applicable to statistical analyses of repeated measures. Cohen’s d is also commonly used in meta-analytical research, and is easily calculated from r, but is not readily interpretable in repeated measure designs. A full discussion on effect size indices was beyond the scope of this article, and the interested reader has been referred elsewhere for more information. Data were independently reviewed by the authors, with complete agreement on the efficacy prior to inclusion in the data set. Analyses were performed using a random effects model, in which studies were considered as the sampling unit, and a fixed effects model, where individual patients in the studies were considered as the sampling unit.