OBSESSIVE–COMPULSIVE SYMPTOMS (OCS) are frequent in patients with schizophrenia.1 This association has become prominent since the introduction of atypical antipsychotics for the treatment of schizophrenia, mainly clozapine.2 Although clozapine has been reported to induce or exacerbate OCS, there is not enough data on the management of these symptoms.

We report the case of a schizophrenia patient without a history of OCS who developed clozapine-induced OCS that responded to valproic acid augmentation.

Mr S, a 51-year-old male patient, first developed paranoid delusions and auditory and visual hallucinations at the age of 23, fulfilling the diagnostic criteria of DSM-IV for schizophrenia. He had been in remission with clozapine 500 mg/day for approximately 1 year before relapse occurred as a result of treatment non-compliance. In April 2011, he was admitted with exacerbation of positive symptoms and was hospitalized. He was started on clozapine 50 mg/day and titrated up to 500 mg/day. A significant improvement was observed in positive symptoms. However, Mr S developed compulsive hand-washing behavior in the 3rd week of the treatment. He had been spending 5–8 h/day washing his hands. He did not have a history of obsessive–compulsive disorder. We assumed clozapine-induced OCS (meeting DSM-IV criteria) and gradually decreased the dosage of clozapine which resulted in aggravation of positive symptoms and elevated mood. Therefore, valproic acid 1000 mg/day was added to the regimen of clozapine 500 mg/day. Two weeks after starting valproic acid (serum level 77.8 mg/L), Mr S's positive symptoms and elevated mood were significantly reduced and his compulsive hand-washing had disappeared. During 3 months of follow up, he remained well under a combined treatment with clozapine (500 mg/day) and valproic acid (1000 mg/day) and there was no reemergence of his compulsion.

Our patient developed hand-washing compulsion during treatment with clozapine which disappeared after augmentation of valproic acid. Although the exact mechanism is not known, the development of OCS associated with clozapine use has been explained by the central serotonergic receptor blocking effects of this drug.1

Although a few case reports have mentioned the efficacy of valproic acid in the treatment of OCD in the literature,3 there is only one case report showing alleviation of clozapine-induced OCD symptoms with valproic acid augmentation in a patient with schizophrenia.4

We suggest that valproic acid may be a choice when treating OCS, which may appear as the adverse effect of atypical antipsychotics in patients with schizophrenia. Randomized controlled trials are required to establish the efficacy of valproic acid in the treatment of antipsychotic-induced OCS before definitive conclusions can be reached.


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  • 1
    Lysaker PH, Whitney KA. Obsessive-compulsive symptoms in schizophrenia: Prevalence, correlates and treatment. Expert Rev. Neurother. 2009; 9: 99107.
  • 2
    Schirmbeck F, Zink M. Clozapine-induced obsessive-compulsive symptoms in schizophrenia: A critical review. Curr. Neuropharmacol. 2012; 10: 8895.
  • 3
    Cora-Locatelli G, Greenberg BD, Martin JD, Murphy DL. Valproate monotherapy in an SRI-intolerant OCD patient. J. Clin. Psychiatry 1998; 59: 82.
  • 4
    Zink M, Englisch S, Knopf U, Kuwilsky A, Dressing H. Augmentation of clozapine with valproic acid for clozapine-induced obsessive-compulsive symptoms. Pharmacopsychiatry 2007; 40: 202203.