Drug-drug interactions between psychotropic medications and oral contraceptives

Georgios Schoretsanitis, Kristina M. Deligiannidis, Michael Paulzen, Edoardo Spina, Jose de Leon

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations


Introduction: This is a comprehensive overview of pharmacokinetic drug-drug interactions (DDIs) involving oral contraceptives (OCs) and psychotropic medications. Areas covered: Medline and Embase from inception to April 2021 were searched for DDIs between OCs and psychotropic medications. They included case reports/series and cross-sectional, cross-over, placebo-controlled studies of patient cohorts and healthy females. We classified DDIs as: combined hormonal contraceptives (CHCs) acting as victim drugs (i.e. affected by psychotropic co-medications), CHCs as perpetrators, (i.e. affecting the activity of psychotropic co-medications), progestin-derivatives as victim drugs and progestin-derivatives affecting psychotropic co-medications. Alteration ratios reflecting changes in pharmacokinetic parameters before and after the DDI were estimated to approximate the extent of the DDI. Expert opinion: Women taking antiepileptic agents with strong to moderate enzyme-inducing properties (carbamazepine, phenobarbital, phenytoin) or those with moderate to mild enzyme-inducing properties (cenobamate, clobazam, eslicarbazepine, felbamate, oxcarbazepine, rufinamide, topiramate) should avoid OCs. Daily doses of cytochrome P450 1A2 substrates including clozapine may need to be reduced by 50% in women taking concomitant CHCs. Compared to CHCs, the propensity of progestin-only pills for DDIs has been investigated less. We provide a summary table for clinicians containing recommendations based on literature and package inserts; whenever evidence was available, we provided dose-correction factors.

Original languageEnglish
Pages (from-to)395-411
Number of pages17
JournalExpert Opinion on Drug Metabolism and Toxicology
Issue number6
StatePublished - 2022

Bibliographical note

Funding Information:
No commercial organizations had any role in the writing of this paper for publication. G Schoretsanitis has served as a consultant for HLS Therapeutics. KM Deligiannidis receives grant support from the U.S. National Institutes of Health (grants R01MH120313 and R01MH118269), the Feinstein Institutes for Medical Research, Vorso Corporation and Sage Therapeutics. She serves as a consultant to Sage Therapeutics, Brii Biosciences and GH Research. M Paulzen received speaker’s fees from Lundbeck, Otsuka, Janssen and Neuraxpharm. In the past few years, E Spina has participated in speakers/advisory boards and lectured, supported by Arcapharma, Janssen Pharmaceuticals, Lundbeck, Otsuka and Recordati. J de Leon personally develops his presentations for lecturing, has never lectured using any pharmaceutical or pharmacogenetic company presentations, and has never been a consultant for pharmacogenetic or pharmaceutical companies. In the past, J de Leon received researcher-initiated grants from Eli Lilly (one ended in 2003 and the other, as co-investigator, ended in 2007); from Roche Molecular Systems, Inc. (ended in 2007); and, in a collaboration with Genomas, Inc., from the NIH Small Business Innovation Research program (ended in 2010). J de Leon has been on the advisory boards of Bristol-Myers Squibb (2003/04) and AstraZeneca (2003). Roche Molecular Systems supported one of his educational presentations, which was published in a peer-reviewed journal (2005). His lectures were supported once by Sandoz (1997), twice by Lundbeck (1999 and 1999), twice by Pfizer (2001 and 2001), three times by Eli Lilly (2003, 2006, and 2006), twice by Janssen (2000 and 2006), once by Bristol-Myers Squibb (2006), and seven times by Roche Molecular Systems, Inc. (once in 2005 and six times in 2006). 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 apart from those disclosed.

Funding Information:
This paper was not funded. The authors acknowledge Lorraine Maw, from the Mental Health Research Center at Eastern State Hospital, who helped in editing the article. The authors also express their gratitude to Elena Scanferla, University of Verona, Verona, for her help in the literature search.

Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.


  • Anticonvulsants
  • antidepressive agents
  • antipsychotic agents
  • benzodiazepines
  • contraceptives/oral
  • drug interactions
  • drug monitoring

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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