Treatment-resistent obsessive-compulsive disorder (OCD): current knowledge and open questions

Objective: Obsessive-compulsive disorder (OCD) is a common psychiatric illness with a lifetime prevalence in the general population of approximately 2-3%. Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral therapy (CBT) in the form of exposure and response prevention (ERP) both represent first-line treatments for OCD. However, unsatisfactory response to these treatments is very common and the evaluation of next-step treatment strategies is highly relevant. The purpose of this paper is to review available data on treatment-resistant OCD and to build a treatment algorithm for those patients who fail to respond to a first SRI trial. Method: We carried out a search on MEDLINE/PUBMED database, selecting meta-analyses, systematic reviews and randomized controlled studies written in English on treatment-resistant OCD. We also considered open-label studies and case series and/or reports, written in English. We reviewed the available evidence for different strategies and tried to delineate an evidence-based treatment algorithm for clinicians. Results: Antipsychotic addition to SRIs and CBT augmentation of drug treatment both are supported by a number of double-blind studies, although differences between antipsychotics seem to exist and the effectiveness of routinely delivered CBT as an adjunct to medication in real world OCD patients with incomplete response to medication need to be replicated. The switch to IV administration of clomipramine may be clinically useful in some cases, although the return to oral formulation often is associated with a relapse. Switching to other first-line agents or to other compounds (such as venlafaxine) is supported by open-label studies or by double-blind studies without a placebo arm. Conclusions: Several evidence-based effective strategies are available to clinicians in case of treatment-resistant OCD. Strengths and limitations of each of the effective strategies are still under study and will be the focus of future comparative trials. There is also a strong need for alternative therapeutic options for OCD patients