Drug-drug interactions between COVID-19 drug therapies and antidepressants

ABSTRACT

Introduction

Antidepressants are widely used for the pharmacological treatment of anxiety and mood disorders. Since the eruption of the SARS-COV-2 pandemic and the later development of targeted treatments against COVID-19, inevitably many patients receive antidepressants as well as targeted treatments against COVID-19 against COVID-19. Co-administration of antidepressants with COVID-19 therapeutics has the potential of drug-drug interactions, of varying severity and clinical significance.

Areas Covered

This is a curated narrative review of the current state of the art regarding drug-drug interactions between COVID-19 therapeutics and medications licensed for the pharmacotherapy of depression. A systematic search of electronic databases, using as keywords the international nonproprietaty names of currently approved COVID-19 therapeutics and antidepressants was performed, and additionally online interaction checker tools were consulted. Derived data were synthesized for each COVID-19 therapeutic and presented with up-to-date guidance.

Expert Opinion

Several COVID-19 therapeutics have potential for drug-drug interactions with antidepressants. Remdesivir and Nirmatrelvir-Ritonavir have the higher risk, whereas several monoclonal antibodies appear safer. The most serious drug-drug interactions (serotonin syndrome and QTc prolongation) require close monitoring; however, DDI toward reducing the efficacy of antidepressants may be difficult to recognize. As COVID-19 treatment protocols take precedence, psychiatrists should exert flexibility in antidepressant use and proactively monitor treatment progress.

KEYWORDS:

• COVID-19
• SARS-CoV-2
• depression
• anxiety
• antidepressants
• drug interactions
• serotonin

Article highlights

• Antidepressants are used to treat anxiety and mood disorders. As these disorders are common, it is highly likely that in the era of COVID-19 pandemic, many patients on antidepressants will need COVID-19 treatment.

• Co-administration of COVID-19 therapeutics and antidepressants may cause drug-drug interactions (DDI). Remdesivir and Nirmatrelvir-Ritonavir are clearly at high risk of DDI and active measures need to be taken.

• Baricitinib and Tofacitinib are at medium, theoretical, risk. Proactive monitoring should be applied but no antidepressant changes are needed, with the exception of antidepressants that are strong CYP inhibitors.

• Molnupiravir, regdanvimab, sotrovimab, tixagevimab/cilgavimab, and casirivimab/imdevimab are considered of low risk for DDI. A point of caution is that many COVID-19 therapeutics are new and involve monoclonal antibodies for which our knowledge about their pharmacokinetics and pharmacodynamics is still developing.

• There is no consistent data that any antidepressant improves COVID-19 course, on the contrary antidepressants with strong CYP-inhibiting properties (fluoxetine, fluvoxamine, paroxetine) have a higher risk for DDI

• Serotonin syndrome and QTc prolongation are the two more serious adverse drug reactions that may appear after a DDI of antidepressants with COVID-19 therapeutics. However, some COVID-19 therapeutics may reduce the efficacy of antidepressant treatment, hence causing a ‘silent’ DDI.

Disclosure statement

N Kokras has received speaker’s fees, consultancy honoraria and travel support from Janssen-Cilag, Lundbeck, Sanofi-Aventis, Medochemie Generics, Elpen, and Vianex. None of those are relevant to this study. 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 or other relationships to disclose.

Additional information

Funding

This paper was not funded.