Objective: We aim to determine the risk of serotonin syndrome with selective monoamine oxidase B inhibitors (MAO-Bi) use, especially when combined with serotonin-acting antidepressants.

Background: Depression is a common non-motor symptom in Parkinson’s disease (PD) and may require treatment with serotonin reuptake inhibitors. MAO-Bi are used extensively in Parkinson’s disease (PD). Higher doses may lead to co-inhibition of MAO-A and theoretical risk of serotonin syndrome. Nevertheless, evidence is scarce on the exact magnitude of this risk, and the safety of combining MAO-Bi and serotonin-acting antidepressants is unclear.

Method: Electronic health records of patients under all public hospitals in Hong Kong were retrieved from the Clinical Data Analysis and Reporting System (CDARS). Patients with a prescription record of the two available MAO-Bi (rasagiline, selegiline) between October 2014 and December 2023 were identified. Concurrent prescription record of serotonin-acting antidepressants and any inpatient episodes with International Classification of Diseases Ninth Revision (ICD-9) code corresponding to serotonin syndrome (333.99 (4)) were examined. Admissions were classified as possible MAO-Bi-related serotonin syndrome if MAO-Bi has been prescribed in the preceding 8 weeks.

Results: A total of 4969 patients (3095 rasagiline, 2496 selegiline) were prescribed an MAO-Bi during the study period, with a total prescription time of 17721.3 patient-years. Six hundred and twenty-five (12.6%) patients (374 (12.1%, 494.9 patient-years) rasagiline, 290 (11.6%, 359.3 patient-years) selegiline) had a concurrent prescription of serotonin-acting antidepressants. Three cases of possible MAOB-i-related serotonin syndrome were identified, with two on concurrent rasagiline and antidepressants (escitalopram and sertraline respectively) and one on selegiline without antidepressant use. Estimated total incidence rate of serotonin syndrome was 1 per 5907 patient-years of MAO-Bi use (1/4793 for rasagiline and 1/8135 for selegiline) and 1/427 patient-years of concurrent MAO-Bi and antidepressant use.

Conclusion: The risk of serotonin syndrome with MAO-Bi in this real-world study appears to be small, even with the concurrent use of serotoninergic antidepressants. Serotoninergic antidepressants should not be withheld if clinically indicated for PD patients on MAO-B inhibitors and vice versa.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/risk-of-serotonin-syndrome-in-the-combined-use-of-selective-monoamine-oxidase-b-inhibitors-and-serotonin-acting-antidepressants/