Obsessive-Compulsive Disorder (OCD) is a common mental disorder and a major cause of disability worldwide. Typically, it has a chronic course, marked by recurrent intrusive thoughts (obsessions) and repetitive behaviors (compulsions). Its pharmacological first line of treatment has been well established for several years now, with the Serotonin Reuptake Inhibitors (SRIs). However, about half of the patients are resistant to this approach, representing a therapeutic challenge for clinicians. Evidence suggests that other medications can augment SRIs, enhancing its effects and achieving a bigger efficacy in these patients’ treatment. Also, there is an increasing interest in neurosurgical interventions in these patients.

The main goal of this work was to assess the clinical efficacy of adjunctive therapeutic strategies in patients with OCD resistant to SRIs.

A literature review was conducted searching PubMed and ScienceDirect databases from the 1st of January 2000 to the 1st of September 2021 to identify clinical trials comparing an active drug/neurosurgical intervention with placebo as an adjunctive therapeutic strategy in SRI-resistant OCD.

Sixteen studies were selected for data extraction, including a total of 585 patients. Risperidone, aripiprazole, N-acetylcysteine, lamotrigine, pindolol, riluzole, memantine and methylphenidate were efficacious for augmenting SRIs in OCD. Ablative surgery (ABL) and deep brain stimulation (DBS) were equal effective in the treatment of refractory OCD.

Several therapeutic options presented as potentially effective in OCD when it is resistant to SRIs, although this is still an area for further research.

No significant relationships.

Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use as monotherapy and adjunctive therapy.

A systematic review and a meta-analysis were conducted on randomized placebo-controlled trials (RCTs) that reported on the efficacy and safety/tolerability of antipsychotics for the treatment of adults with MDD. Data of both monotherapy and adjunctive antipsychotic use were extracted, but analyzed separately using a random-effects model. Co-primary outcomes were study-defined-treatment response and intolerability-related discontinuation. We also illustrated the risk/benefit balance of antipsychotics for MDD, using two-dimensional graphs representing the primary efficacy and safety/tolerability outcome. Secondary outcomes included psychopathology, remission, all-cause-discontinuation, inefficacy-related discontinuation, and adverse events.

Forty-five RCTs with 12 724 patients were included in the analysis. In monotherapy (studies = 13, n = 4375), amisulpride [1.99 (1.55–2.55)], sulpiride [1.50 (1.03–2.17)], and quetiapine [1.48 (1.23–1.78)] were significantly superior to placebo regarding treatment response. However, intolerability-related discontinuations were significantly higher compared to placebo with amisulpride and quetiapine. In adjunctive therapy (studies = 32, n = 8349), ziprasidone [1.80 (1.07–3.04)], risperidone [1.59 (1.19–2.14)], aripiprazole [1.54 (1.35–1.76)], brexpiprazole [1.41 (1.21–1.66)], cariprazine [1.27 (1.07–1.52)], and quetiapine [1.23 (1.08–1.41)] were significantly superior to placebo regarding treatment response. However, of these antipsychotics that were superior to placebo, only risperidone was equivalent to placebo regarding discontinuation due to intolerability, while the other antipsychotics were inferior.

Results suggest that there are significant differences regarding the risk/benefit ratio among antipsychotics for MDD, which should inform clinical care.