Drug-drug Interactions between COVID-19 Treatments and Antidepressants, Mood Stabilizers/Anticonvulsants, and Benzodiazepines: Integrated Evidence from 3 Databases

Pharmacopsychiatry. 2022 Jan;55(1):40-47. doi: 10.1055/a-1492-3293. Epub 2021 Jun 25.


Introduction: The SARS-CoV-2 pandemic with psychiatric comorbidities leads to a scenario in which the use of psychotropic drugs may be required. This requires the support of evidence-based medicine to take into account possible interactions between antidepressants, mood stabilizers, benzodiazepines, and coronavirus infection treatments.

Methods: Three databases were consulted: (a) Lexicomp Drug Interactions, (b) Micromedex Solutions Drugs Interactions, (c)Liverpool Drug Interaction Group for COVID-19 therapies. The CredibleMeds QTDrugs List was also queried. Hydroxychloroquine, chloroquine, azithromycin, lopinavir-ritonavir, remdesivir, favipiravir, tocilizumab, baricitinib, anakinra, and dexamethasone - drugs used for SARS-CoV-2 - were analyzed, and consensus recommendations are made.

Results: The potential interactions of agomelatine, desvenlafaxine, duloxetine, milnacipran, and vortioxetine with COVID-19 treatments shall be considered less risky. Antidepressant interactions with hydroxychloroquine, chloroquine, and azithromycin enhance the risk of QT prolongation, and ECG monitoring is advised for most antidepressants. Antidepressants with lopinavir/ritonavir involve multiple CYP enzyme interactions (except with milnacipran). Gabapentin, oxcarbazepine, pregabalin, topiramate, and zonisamide are safe treatment options that have no significant interactions with COVID-19 treatments. Lithium is contraindicated with hydroxychloroquine, chloroquine, and azithromycin. Precaution should be taken in using valproic acid with lopinavir-ritonavir. The use of benzodiazepines does not present a risk of drug interaction with COVID-19 treatments, except lopinavir/ritonavir.

Conclusions: Clinicians prescribing antidepressants, mood stabilizers/anticonvulsants, and benzodiazepines, should be aware of the probable risk of drug-drug interaction with COVID-19 medications and may benefit from heeding these recommendations for use to ensure patient safety.

MeSH terms

  • Anticonvulsants
  • Antidepressive Agents
  • Antiviral Agents / therapeutic use
  • Benzodiazepines
  • COVID-19 Drug Treatment*
  • Drug Interactions
  • Humans
  • SARS-CoV-2


  • Anticonvulsants
  • Antidepressive Agents
  • Antiviral Agents
  • Benzodiazepines