Letters to the Editor
Obsessive–Compulsive Symptoms in Schizophrenia Induced by Risperidone and Responding to Fluoxetine
Dear Editor:
Risperidone has been reported to induce or exacerbate obsessive–compulsive symptoms in schizophrenia patients (1) but may also be efficacious as an augmentation strategy in refractory obsessive–compulsive disorder (OCD) (2). Atypical antipsychotics such as risperidone may induce OC symptoms at low dosages, owing to high 5-HT2–D2 antagonism, whereas they may improve OC symptoms at high dosages, owing to high D2 antagonism (3). For instance, a patient with bipolar disorder was reported to present OC symptoms with low-dosage risperidone; however, these symptoms reversed at higher dosages, suggesting an inverse dosage–response relation (3). We report the case of a schizophrenia patient without a history of obsessions or compulsions who developed risperidone-induced OC symptoms that responded to fluoxetine.
Case Report
Mr A, a 49-year-old married man, working full-time, has a 26-year history of chronic schizophrenia. His medical history revealed essential hypertension. He was stable on intramuscular (IM) haloperidol decanoate 270 to 350 mg given every 4 weeks for over 10 years. After he developed tardive dyskinesia, haloperidol decanoate was switched to risperidone 6 mg daily. His anti- hypertensive medications, taken for several years, remained constant. After 3 weeks of risperidone, he developed ideas of reference. Risperidone was increased to 8 mg daily. One week later, the ideas of reference took on delusional proportions and obsessional qualities. Risperidone was increased over the next 8 weeks to 12.5 mg daily. Valproic Acid was then started (for putative antipsychotic- induced therapeutic tolerance [4]) and titrated to 1500 mg daily over 3 weeks. Six weeks after the risperidone increase to 12.5 mg daily, and 14 weeks after risperidone initiation, Mr A developed obsessional thinking. He described his obsessions as recurrent, intrusive “crazy thoughts of killing [his] wife” that occupied much of his time and generated anxiety. Fluoxetine 10 mg every 2 days was started. Over the next 4 weeks, the obsessions persisted without psychotic symptoms. Fluoxetine was increased to 10 mg daily, and 3 weeks later his obsessions completely resolved. Nine months after fluoxetine initiation, Mr A was stable on the same medication regimen.
The occurrence of OC symptoms in chronic schizophrenia ranges from 7.8% to 46.6% (5). In this report, we suggest that the OC symptoms resolved through 2 possible mechanisms of fluoxetine: first, increased serotonin through 5-HT reuptake and, second, inhibited cytochorme P450 enzyme 2D6 (which would increase risperidone concentrations because risperidone is metabolized by 2D6). This last effect of fluoxetine would be in keeping with the inverse dosage–response relationship of risperidone; that is, at high dosages, D2 antagonism improves OC symptoms (3).
References
1. Lykouras L, Zervas IM, Gournellis R, Malliouri M, Rabavilas A. Olanzapine and obsessive–compulsive symptoms. Eur Neuropsychopharmol 2000;10:385–7.
2. McDougall CJ, Epperson CN, Pelton GH, Wasylink S, Price LH. A double-blind placebo-controlled study of risperidone addition in serotonin-reuptake inhibitor-refractory obsessive–compulsive disorder. Arch Gen Psychiatry 2000;57:794–801.
3. Ramasubbu R, Ravindran A, Lapierre Y. Serotonin and dopamine antagonism in obsessive–compulsive disorder: effect of atypical antipsychotic drugs. Pharmacopsychiatry 2000;33:236–8.
4. Chouinard G, Sultan S. Treatment of supersensitivity psychosis with antiepileptic drugs. Report of a series of 43 cases. Psychopharmacol Bull 1990;26:337–41.
5. Eisen JL, Beer DA, Pato MT, Venditto TA, Rasmussen SA. Obsessive–compulsive disorder in patients with schizophrenia or schizoaffective disorder. Am J Psychiatry 1997;154:271–3.
Emmanuelle Levy, MD, FRCPC
Howard C Margolese, MD, CM, FRCPC
Sarah Sultan, MD, FRCPC
Montreal, Quebec
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