https://orcid.org/0000-0001-9327-6660
![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
ABSTRACT
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.
Article highlights
The co-occurrence of depression and various neurological disorders is commonly observed in clinical practice, particularly among aging populations. Consequently, antidepressants are frequently co-prescribed with neurological medications, increasing the risk of drug interactions (DIs).
Some newer antidepressants can induce pharmacokinetic (PK) interactions by inhibiting specific cytochrome P450 (CYP) enzymes. In this context, compounds such as fluoxetine, paroxetine, fluvoxamine, duloxetine, and bupropion are considered moderate to potent inhibitors of several CYP isoforms and may be implicated in clinically relevant interactions with neurological drugs metabolized via these pathways.
As newer antidepressants undergo extensive metabolism via various CYP isoforms, concomitant treatment with neurological medications that act as inhibitors or inducers of these enzymes may alter antidepressant plasma concentrations. However, given the relatively wide safety margin of newer antidepressants, the clinical consequences of such PK modifications are unlikely to be significant.
Serotonergic antidepressants also pose a risk of triggering serotonin syndrome, a potentially life-threatening condition, when co-administered with monoamine oxidase B inhibitors or triptans. These interactions are typically listed as warnings or contraindications in drug labeling.
Further studies are needed to clarify the clinical significance of efflux transporters, such as P-glycoprotein, in mediating interactions between newer antidepressants and neurological medications.
Clinicians must remain alert to potential DIs involving antidepressants and neurological agents. A comprehensive understanding of both PK and pharmacodynamic (PD) mechanisms, along with proactive strategies, such as pharmacogenetic testing, therapeutic drug monitoring, the use of interaction databases, and close clinical observation, can aid in predicting, preventing, and managing adverse DIs.
Minimizing unnecessary polypharmacy can greatly reduce the likelihood of harmful interactions. Regular medication reviews and deprescribing practices are essential strategies, particularly for older adults with complex medication regimens.
There is a clear need for more pharmacoepidemiological studies examining the combined use of newer antidepressants and neurological drugs, with a focus on both PK and PD interactions.
Declaration of interest
M.A. Barbieri declares no conflict of interest. M. Alborghetti has been sponsored by Lundbeck Italia and NextStepPharma for educational activity, received travel grants fromZambon, Polifarma and Lundbeck Italia, and research grants from Sapienza University of Rome, outside of the present work. F. Nicoletti has been a consultant and/or a speaker and/or has received research grants from Lundbeck, Janssen, Otsuka, Angelini, Neuroaxpharma, Arcapharma, and research funding from PNRR by European Union, Sapienza University of Rome, and Italian Ministry of Health. In the past few years, E. Spina has participated in speakers/advisory boards and lectures supported by Angelini, Janssen Pharmaceuticals, Lundbeck, Rovi, UCB Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.
Author contributions
M. Alborghetti, M.A. Barbieri, F. Nicoletti, and E. Spina made substantial contributions to the conception and design of the work and to the acquisition and interpretation of data. All authors were involved in drafting the manuscript and revising it critically for important intellectual content, provided final approval of the version to be published, and agreed to be accountable for all aspects of the work.
Acknowledgments
Artificial intelligence (ChatGPT OpenAI, version GPT-5) was employed exclusively for language improvement of the text. All aspects of the study, including conception and design, interpretation of results, and formulation of conclusions, were carried out entirely by the authors without the use of AI tools. The authors take full responsibility for the integrity and accuracy of the work.