Antipsychotics for Obsessive-Compulsive Disorder

I read with interest the thoughtful review Diagnosis and Management of Obsessive-Compulsive Disorder in the Primary Care Setting.¹ The authors accurately state that because first-line treatments, namely selective serotonin reuptake inhibitors (SSRIs) and exposure and response prevention psychotherapy, often yield only a partial response, many patients require additional therapy augmentation. Surprisingly, the authors do not mention antipsychotics, even though they discuss options with less supporting evidence.

Among the augmentation choices proposed in the treatment algorithm is the combination of clomipramine and SSRIs. This strategy is endorsed by the 2007 American Psychiatric Association practice guidelines but has little evidence, especially when compared with antipsychotic augmentation.² Even the common practice of switching to clomipramine alone in the case of unsatisfactory response to one or more SSRIs is contested by a network meta-analysis showing no convincing evidence that clomipramine is superior to SSRIs.³

Augmentation strategies are commonly divided into glutamatergic agents (eg, memantine, topiramate, lamotrigine) and dopamine antagonists (ie, antipsychotic medications).⁴ Although experts differ in their preference between the two classes,^5,6 there appears to be a consensus that antipsychotics are evidence-based augmentation therapies for obsessive-compulsive disorder. Aripiprazole and risperidone have the most consistent evidence of effectiveness.^2,5

Antipsychotics have a higher risk of adverse effects than SSRIs and several other agents mentioned in the article. However, clomipramine also carries a significantly higher risk of adverse effects than SSRIs. Although augmentation is more likely to be prescribed by psychiatrists than primary care clinicians, recognizing that antipsychotic augmentation is an evidence-based practice would foster a good therapeutic alliance and follow-up.

We are grateful for these comments addressing the use of antipsychotics for augmentation of therapy. We agree that it is important for primary care clinicians to be aware of augmentation with antipsychotics for individuals with obsessive-compulsive disorder. Although not explicitly stated, we categorized antipsychotics as neuroleptic agents within the treatment section of the article. Clomipramine is approved by the US Food and Drug Administration as treatment for obsessive-compulsive disorder, despite its significant adverse effects, which were taken into consideration when creating the algorithm. Although there is growing evidence for the use of antipsychotics for augmentation, the prescribing of these drugs may be limited in a busy primary care practice given the high adverse effect burden (particularly weight gain and diabetes) that requires closer monitoring.¹

Ultimately, a decision to start augmentation with pharmacotherapy should be made with careful consideration of potential adverse effects and include an integrated psychiatry team or psychiatry consultation. Further research into intraclass and interclass differences, in addition to head-to-head clinical trials, is needed to provide a more precise treatment algorithm.