Current Psychiatry Reports

, 16:510 | Cite as

Second Generation Antipsychotic-Induced Obsessive-Compulsive Symptoms in Schizophrenia: A Review of the Experimental Literature

  • Trehani M. Fonseka
  • Margaret A. Richter
  • Daniel J. MüllerEmail author
Genetic Disorders (W Berrettini, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Genetic Disorders


Second generation antipsychotics (SGAs) have been implicated in the de novo emergence and exacerbation of obsessive-compulsive symptoms (OCS) in patients with schizophrenia. Among SGAs, clozapine, olanzapine, and risperidone are the most prominent agents associated with these sequelae, according to case reports. Comorbid OCS can impede recovery by compromising treatment benefits, medication compliance, and clinical prognoses. Previous reviews of SGA-induced OCS have predominantly focused on descriptive case reports, with limited attention paid toward experimental findings. To address this paucity of data, we sought to review the effects of SGAs on OCS in schizophrenia in the experimental literature, while addressing the role of different treatment (duration, dose, serum levels) and pharmacogenetic factors. Our findings suggest that clozapine confers the greatest risk of OCS in schizophrenia, with 20 to 28 % of clozapine-treated patients experiencing de novo OCS, in addition to 10 to 18 % incurring an exacerbation of pre-existing OCS. Clozapine can also yield full threshold obsessive-compulsive disorder (OCD), in some cases. Olanzapine is another high risk drug for secondary OCS which occurs in 11 to 20 % of schizophrenic patients receiving olanzapine therapy. At this time, there is insufficient experimental evidence to characterize the effects of other SGAs on OCS. Despite some experimental support for the involvement of longer treatment duration and genetic factors in mediating drug-induced OCS, more research is needed to clearly elucidate these associations. Based on these results, schizophrenic patients should be routinely monitored for OCS throughout the course of SGA treatment, particularly when clozapine or olanzapine is administered.


Second generation antipsychotic Clozapine Olanzapine Obsessive-compulsive disorder Schizophrenia Side effect 


Compliance with Ethics Guidelines

Conflict of Interest

Trehani M. Fonseka and Daniel J. Müller declare that they have no conflict of interest. Daniel J. Müller hase received frunding from the Canadian Institutes of Health Research (CIHR), the Brain & Behaviour Research Foundation (USA), the Ontario Mental Health Foundation (Canada), and the Ministry of Research and Innovation of Ontario (Canada).

Margaret A. Richter has received grants from the Ontario Mental Health Foundation, Canadian Institutes of Health Research and honoraria payments from Lundbeck.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Trehani M. Fonseka
    • 1
  • Margaret A. Richter
    • 2
    • 3
  • Daniel J. Müller
    • 1
    • 3
    Email author
  1. 1.Campbell Family Mental Health Research Institute, Center for Addiction and Mental HealthTorontoCanada
  2. 2.Frederick W. Thompson Anxiety Disorders Centre, Department of Psychiatry, Sunnybrook Health Sciences CentreUniversity of TorontoTorontoCanada
  3. 3.Department of PsychiatryUniversity of TorontoTorontoCanada

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