Neurobiology and Effectiveness of Antipsychotic Drugs in Resistant Obsessive-Compulsive Disorder: A Systematic Review

Abstract

Aims of the StudyTo synthesize in a comprehensive review, the mechanistic hypotheses of antipsychotic potential activity in OCD and to summarize clinical trials on the effectiveness of antipsychotic drugs in OCD, in monotherapy or in combination with SSRIs.A systematic review of the literature was conducted using PRISMA criteria. The paradigm search was "obsessive compulsive disorder and antipsychotic agents". Medline, Cochrane and Web of science databases were explored without date or language restriction. Case reports, open label studies and randomized double-blind controlled trials were included in the qualitative review.Unlike the classical serotonergic hypothesis, OCD may result from striatal dopaminergic hyperactivity, modulated in some patients by an underlying serotonergic hypo activity. In the treatment of resistant OCD, most studies report the effectiveness of first-generation antipsychotic (haloperidol, amisulpride) and some second-generation antipsychotics (risperidone, olanzapine, aripiprazole, quetiapine) in combination with an SSRI. Moreover, in case reports, recrudescence or onset of OCD symptoms in patients with schizophrenia have been described in a switch from first generation antipsychotic medication to olanzapine, risperidone, aripiprazole or clozapine, but not within a switch to amisulpride or quetiapine.These preliminary results on the use of antipsychotic medication in OCD deserve further investigation for potential guideline updates.Obsessive-Compulsive Disorder (OCD) is "the presence of recurrent ego-dystonic and intrusive thoughts or images (obsessions), with ritualized behaviors (compulsions) performed in order to neutralize obsessive thoughts" [1]. The lifetime prevalence of OCD in France in 2006 was 2 to 3%, its prevalence over a period of 6 months was 1 to 2% and the sex ratio is 1 [2]. In the USA, in 2005, OCD was recognized as a fairly common psychological disorder with reported lifetime prevalence between 1.6 and 3.3%, and 1 year prevalence between 1.0 and 2.1% "Resistant OCD" may be defined as OCD whose symptoms persist after treatment by SSRIs in high doses for at least 8 weeks [2]. The SSRI response-rate is only 40% to 60% of patients [4]. Whereas resistant OCD is typically explained by serotonin mechanisms, another neurobiological mechanisms are involved [5]. For example, in some patients, dopaminergic hyperactivity modulated by an underlying serotonergic hypo activity has been suggested [6].Antipsychotics have been suggested as second-line treatment in resistant OCD with a controversial effectiveness [7]. At first sight, risperidone's effectiveness in resistant OCD [8] seems paradoxical: if OCD is conceived as a serotonin deficiency, the coprescription of a 5-HT antagonist with a SSRI should worsen OCD symptomatology. Moreover, low doses of risperidone (<3 mg/d) have found to be the best effective where the anti-5-HT2A activity is optimal with a very low anti-D2 activity [9,10]. Finally, some second-generation antipsychotics have been involved in de novo OCD genesis in psyc...