Clozapine-induced obsessive–compulsive symptoms: mechanisms and treatment

Determining the origin of OCS in individuals with schizophrenia is a clinical challenge, because OCS can be an idiopathic component of positive symptoms or an adverse effect of antipsychotic medications.1 Clozapine is the antipsychotic most well known to induce OCS.2,3 Although the prevalence of OCS among patients treated with clozapine tends to vary widely owing to methodological heterogeneity among studies, a recent study reported a mid-point prevalence of 47%.4 Mechanisms underlying clozapineinduced OCS have not been fully delineated. [...]genetics may play a role, according to a finding that individuals with polymorphisms in the genes that regulate glutamate transmission, such as SLC1A1 and GRIN2B, were more susceptible to clozapine-induced OCS.19 Findings of abnormal brain activation patterns and neurocognitive deficits associated with treatment with antiserotonergic antipsychotics (e.g., clozapine and olanzapine) also need to be considered in relation to clozapine-induced OCS.7,10 Clozapine-induced OCS may improve if the dose is reduced or discontinued.2,3 However, some case reports found OCS to improve when the dose of clozapine was increased.2 The conflicting results may be explained by the heterogeneous etiology of OCS.1,3 As clozapine dose reduction or discontinuation carries the risk of exacerbation of target symptoms (e.g., psychosis), other treatment options may be preferred. Add-on SSRIs can be effective in treating clozapine-induced OCS.2 Mechanisms may involve enhancement of 5-HT neurotransmission and normalization of 5-HT2C receptor function.14 Of note, SSRIs, in particular fluvoxamine, can increase clozapine blood levels, and given that higher plasma clozapine and norclozapine concentrations may be associated with the development of clozapine-induced OCS,20 careful drug monitoring should be considered when using add-on SSRIs.