Ondansetron augmentation for the management of obsessive-compulsive disorder in a patient with treatment-resistant schizophrenia

Dear Editor

We present a case of a 64-year-old man with comorbid treatment-resistant conditions of schizophrenia and obsessive-compulsive disorder (OCD) who has had a modest response to augmentation with ondansetron.

Schizophrenia and OCD interweave in several ways. It is known that up to 52% of patients with schizophrenia have either obsessive-compulsive (OC) symptoms or disorder (Bottas et al., 2005). From a functional pathophysiological point of view, both share abnormalities in the cortico-striatal and thalamo-cortical pathway (Bottas et al., 2005). OC symptoms reduce when adding antipsychotics to selective serotonin reuptake inhibitors (SSRIs) (Bottas et al., 2005).

Ondansetron is a 5-HT3 receptor antagonist commonly used as an antiemetic. Ondansetron in combination with SSRIs will increase the serotonin levels in the brain. This provides the rationale for the combination of ondansetron with SSRIs in the treatment of OCD. Ondansetron has a weak downstream inhibitory effect on dopaminergic neurotransmission, indirectly inhibiting the cortico-mesolimbic dopamine. Studies have used ondansetron to treat schizophrenia as monotherapy and as antipsychotic augmentation (Zhang et al., 2006). Studies using variable-dose ondansetron show its benefits in patients with treatment-resistant OCD (Andrade, 2015).

Mr X was an inpatient for the management of treatment-resistant schizophrenia. He had comorbid symptoms meeting Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-V) criteria for OCD, and the course of OCD symptoms were unrelated to his clozapine treatment; however, clozapine possibly exacerbated OCD symptoms. His OCD symptoms included obsessional doubts and compulsive checking. His psychotic symptoms included auditory hallucinations which continued despite being on an adequate dose of clozapine in combination with amisulpride and a trial of electro convulsive therapy (ECT). Prior to the trial, he reported that OCD symptoms were more distressing than psychotic symptoms. The disabling OCD symptoms persisted despite adequate trials of clomipramine, SSRIs and memantine.

At the time of commencement of ondansetron, he was taking clozapine, sodium valproate and clomipramine and he scored 30 in the Yale Brown Obsessive Compulsive Scale (Y-BOCS). After checking electrocardiogram (ECG), we commenced ondansetron 2 mg daily and titrated to 8 mg daily. Subjective and objective improvement was observed in his OCD symptoms with reduction of Y-BOCS score to 22 after 4 weeks. Mr X did not report any side effects with ondansetron and reported reduction in the threatening persecutory auditory hallucinations. He reported an increased capacity to resist his OCD symptoms, including more days where he was not overwhelmed with symptoms.

The use of ondansetron for the management of OCD with comorbid treatment-resistant schizophrenia may be promising; its efficacy and tolerability requires clinical trials.