Interaction between Monoamine Oxidase B Inhibitors and Selective Serotonin Reuptake Inhibitors

Background: Monoamine oxidase B (MAO-B) inhibitors are used to treat the motor symptoms of Parkinson disease. Depression is commonly associated with Parkinson disease, and selective serotonin reuptake inhibitors (SSRIs) are often used for its management. Tertiary sources warn that the combination of MAO-B inhibitors and SSRIs can result in increased serotonergic effects, leading to serotonin syndrome. Objective: To explore the mechanism, clinical significance, and management of this potential drug interaction through a review of the supporting evidence. Data Sources: PubMed, MEDLINE (1946 forward), Embase (1947 forward), PsycINFO (1806 forward), and International Pharmaceutical Abstracts (1970 forward) were searched on February 4, 2017. Study Selection and Data Extraction: Studies and case reports describing aspects of the potential interaction between MAO-B inhibitors and SSRIs in patients with Parkinson disease and published in English were identified by both title and abstract. Data Synthesis: The search identified 8 studies evaluating the potential interaction between SSRIs and the MAO-B inhibitors selegiline and rasagiline. The largest, a retrospective cohort study of 1504 patients with Parkinson disease, found no cases of serotonin syndrome with coadministration of rasagiline and an SSRI. A survey of 63 investigators in the Parkinson Study Group identified 11 potential cases of serotonin syndrome among 4568 patients treated with the combination of selegiline and antidepressants (including SSRIs). In addition, 17 case reports describing the onset of serotonin syndrome with coadministration of an SSRI and either selegiline or rasagiline were identified. Following discontinuation or dose reduction of one or both of the agents, the symptoms of serotonin syndrome gradually resolved in most cases, with none being fatal. Conclusions: According to the literature, serotonin syndrome occurs rarely, and the combination of SSRI and MAO-B inhibitor is well tolerated. Therefore, SSRIs and MAO-B inhibitors can be coadministered, provided that their recommended doses are not exceeded and the SSRI dose is kept at the lower end of the therapeutic range. Among the SSRIs, citalopram and sertraline may be preferred.