Exploring drug interactions between newer antidepressants and medications used to treat neurological disorders

Introduction: This review examines clinically relevant drug interactions (DIs) between newer antidepressants and medications used to manage neurological disorders frequently comorbid with depression, including Parkinson’s disease, Alzheimer’s disease, migraine, multiple sclerosis, and neuropathic pain. Areas covered: Articles were obtained from PubMed®, Web of Science, SCOPUS, and Google Scholar searches performed for each of the newer antidepressants and neurological medications. The pharmacokinetic (PK) and pharmacodynamic (PD) mechanisms underlying these DIs were summarized. Some newer antidepressants, such as fluoxetine, paroxetine, fluvoxamine, duloxetine, and bupropion, are moderate to potent inhibitors of various cytochrome P450 (CYP) isoenzymes and can produce clinically relevant interactions with neurologic drugs metabolized by these pathways. In addition, serotonergic antidepressants can precipitate potentially fatal serotonin syndrome when co-administered with monoamine-oxidase-B inhibitors or triptans; these interactions are noted as warnings or contraindications in product labeling. Expert opinion: Clinicians must remain alert to possible DIs between antidepressants and neurological medications. Understanding PK and PD principles, coupled with proactive measures, such as pharmacogenetic testing, therapeutic drug monitoring, use of drug-interaction databases, and close clinical observation, can help to predict, prevent, and manage adverse interactions. Avoiding unnecessary polypharmacy, together with regular medication reviews and deprescribing, is particularly important for older adults with multiple comorbidities.