Reply to "Risperidone-induced obsessive-compulsive symptoms: serotonin-dopamine imbalance?".

Abstract

To the Editors: We appreciate Dr Duggal’s comments about our recent article. He mentions that we focus on an association between higher doses of risperidone and emergence of obsessive compulsive (OC) symptoms, found in all 6 patients with schizophrenic disorder we presented. He also elaborates further on our postulation regarding a serotonin-dopamine imbalance as a possible mechanism of OC symptom production raising important issues. He reports on a case in which OC symptoms emerged at a dose of 4 mg/d, which is apparently not a low dose, but they did not reemerge at a dose of 6 mg/d. The same was the case for another patient (doses: 1 and 3 mg/d, respectively). A MEDLINE search of the literature from 1990 to 2002 disclosed 10 additional reports. These reports included 10 cases in which a de novo emergence or exacerbation of OC symptoms during treatment with risperidone emerged. In all but 1 case, the dose was 3 mg/d or higher: 6 mg/d, 4 patients; 5 mg/d, one patient; 4 mg/d, 3 patients; and 1 mg/day, 1 patient. It is worth noting that contrary to risperidone, clozapine induced OC symptoms (30 cases) at a broad dosage spectrum. Another observation was that, in most cases in risperidone, OC symptoms emerged shortly after initiation of treatment and rapid escalation of the dose. As Dr. Duggal pointed out, the 5-HT2A/D2 antagonism of risperidone differs concerning low and high doses. It is worth noting that in 16 cases reported in the literature, including ours, the diagnoses were as follows: schizophrenia, 10 patients; bipolar disorder + tardive dyskinesia, 1 patient; psychotic disorder not otherwise specified (NOS) + obsessive compulsive disorder (OCD), 1 patient; depression with psychotic features, 1 patient; OCD, 1 patient; schizoaffective disorder bipolar type, 1 patient; and bipolar II disorder, 1 patient. The last 2 patients mentioned by Duggal did not develop OC symptoms on reinstitution of risperidone at a higher dose. Both patients had a diagnosis other than schizophrenia and differed from their remaining counterparts in that they were on lithium therapy. The neurobiologic substrate of the primary disorder should be considered as a potent contributing factor in the production of OC symptoms. Typical antipsychotics and other psychotropic drugs, for example, serotonergics and lithium, may modify it. Having in mind the above, differences in terms of neurobiologic substrate and the use of lithium that characterized the 2 patients should be taken into account. Due to the complexity of serotonergic neurotransmitter system, the limited knowledge of the dopamine abnormalities in OCD, and involvement of the non-5-HT2 and D2 receptors and other neurotransmitter systems, identification of pathogenetic mechanisms involved in the induction of OC symptoms is apparently difficult. However, investigations of the dose-response between OC symptoms and atypical antipsychotics are recommended.