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A large subgroup of schizophrenic patients develops obsessive-compulsive symptoms (OCS) during treatment with second-generation antipsychotics (SGA). A genetic risk factor for these secondary OCS was recently described in the gene SLC1A1 encoding the neuronal glutamate transporter excitatory amino acid carrier 1. The aim of this study was to replicate these findings in a European sample.A total of 103 schizophrenic patients treated with SGAs were included. Three single nucleotide polymorphisms in SLC1A1 (rs2228622, rs3780412 and rs3780413), which had been associated with SGA-induced OCS, were investigated. Single marker and haplotype analyses were tested with logistic regressions using age, sex and medication type as covariates.Treatment with markedly antiserotonergic SGAs such as clozapine was more prevalent in the subgroup of patients with comorbid OCS (P<0.001). The dosage and duration of clozapine treatment correlated significantly with the severity of OCS. In contrast to the Asian sample, no genetic associations were found with OCS.Larger samples are necessary to unravel the interplay of pharmacological and genetic risk factors for OCS in schizophrenia. [ABSTRACT FROM AUTHOR]

Many schizophrenic patients have comorbid obsessive-compulsive syndromes (OCS) frequently associated with antiserotonergic second-generation antipsychotics such as clozapine and olanzapine. Whereas cognitive behavioral therapy and antiobsessive antidepressants brought up inconsistent results, pharmacological add-on strategies were able to alleviate OCS. One suggestive agent for antiobsessive add-on treatment is aripiprazole, a partial agonist at dopamine and serotonin receptors. Here, we summarize the course of a patient with paranoid schizophrenia. She developed OCS during long-term treatment with olanzapine at 20 mg/d over a period of 10 years. Baseline assessment showed severe obsessions (Yale Brown Obsessive Compulsive Scale (YBOCS) subscale score : 13) and compulsions (YBOCS subscale score : 10), whereas the psychotic syndrome was compensated (Positive and Negative Syndrome Scale, 11/17/28). The combination with aripiprazole (15 mg/) over a period of 12 weeks resulted in a marked improvement of OCS (YBOCS, 8/3) and some further improvement of the psychotic symptoms (Positive and Negative Syndrome Scale, 9/13/27). This observation points toward an antiobsessive potency of aripiprazole in combination with olanzapine, quite similar to approaches involving clozapine. Hence, the proposed strategy should be further evaluated in prospective controlled trials.

Patients with schizophrenia often experience comorbid obsessive-compulsive syndromes (OCSs). Within these patients, a significant subgroup developed secondary OCS during treatment with antiserotonergic, atypical antipsychotic agents such as clozapine. Although cognitive behavioral therapy and antiobsessive antidepressants brought up inconsistent results, in some cases, dose reductions of clozapine in combination approaches were able to alleviate OCS. One suggestive agent for antiobsessive add-on treatment is aripiprazole, a partial agonist at dopamine and serotonin receptors.Here, we summarize the courses of 7 patients (6 men; mean age, 37 years; mean duration of psychotic illness, 17 years). They had been treated with clozapine for 9 years. The distressing and treatment-resistant comorbidity with OCS emerged approximately 4 years after the start of clozapine therapy. During combined treatment with mean doses of 22.9 mg of aripiprazole for 9.7 weeks, we assessed a small yet statistically not significant improvement of the psychotic disorder, whereas a marked reduction of obsessions and significant improvements of compulsions could be observed. The mean total Yale Brown Obsessive Compulsive Rating Scale decreased from 18.7 to 12.4 (P = 0.003).These data support the findings of 2 previous case reports and point toward an antiobsessive potency of aripiprazole. The relevant disabling comorbidities of psychosis and OCS need further investigation with multimodal neurobiological approaches. The proposed strategy should be further evaluated in prospective controlled trials with severity of comorbid OCS as a primary end point.