Effects of Antipsychotic Treatment on Obsessive-Compulsive Symptoms

A large subgroup of schizophrenia patients suffers from obsessive-compulsive symptoms (OCS). The patterns of OCS onset and longitudinal course significantly differ, most likely due to a so far incompletely understood interaction of genetic and environmental factors. One subgroup experiences the de novo onset or marked aggravation of pre-existing OCS during treatment with second-generation antipsychotics (SGAs). Substances such as clozapine and olanzapine balance their antidopaminergic effects with a potent antagonism at serotonin receptors. It has been proposed that these pharmacodynamic properties might have a pro-obsessive effect. Several epidemiological and pharmacological arguments substantiate this assumption of second-onset OCS as a widely under-recognised adverse event. Patients who suffer from SGA-induced OCS present with more pronounced cognitive deficits and show differential patterns of brain activation during functional magnetic resonance imaging using OCS-sensitive tasks. Specific genetic risk factors seem to dispose patients with schizophrenia to develop OCS during SGA treatment. Further research is needed to investigate possible gene and environment interactions in more detail. With respect to practical implications, clinicians should consider the risk of second-onset OCS prior to treatment initiation and provide this information to the patient as part of shared decision-making. Before the start of clozapine treatment, the antipsychotic of first choice in treatment-resistant schizophrenia, a careful diagnostic characterisation of OCS and neurocognitive abilities seems advisable. Longitudinal monitoring should aim at the early detection of OCS and evaluation of anti-obsessive interventions. This could include minimally sufficient dosages of pro-obsessive SGAs, which might be achieved by rational strategies of polypharmacy.