Drug interactions between hormonal contraceptives and psychotropic drugs: a systematic review
Open accessAbstract
Objective To examine whether the co-administration of hormonal contraceptives (HC) and psychotropic drugs commonly used to treat anxiety and/or depression results in safety or efficacy concerns for either drug.Methods We searched PubMed and Cochrane libraries for clinical or pharmacokinetic (PK) studies that examined co-administration of any HC with psychotropic drugs [selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), oral benzodiazepines, bupropion, mirtazapine, trazadone, buspirone, hydroxyzine, monoamine oxidase inhibitors (MAOIs), or atypical antipsychotics] in reproductive aged women.Results Of 555 articles identified, 22 articles (18 studies) met inclusion criteria. We identified 5 studies on SSRIs, four on TCAs, one on bupropion, three on atypical antipsychotics and five on oral benzodiazepines. No articles met inclusion criteria for SNRIs, mirtazapine, trazadone, buspirone, hydroxyzine or MAOIs. Overall, clinical studies did not demonstrate differences in unintended pregnancy rates when HCs were administered with and without psychotropic drugs or in psychotropic drug treatment outcomes when psychotropic drugs were administered with and without HCs. PK studies did not demonstrate changes in drug exposure related to contraceptive safety, contraceptive effectiveness or psychotropic drug effectiveness for most classes of psychotropic drugs. However, limited PK data raise concern for HCs increasing systemic exposure of amitriptyline and imipramine (both TCAs), theoretically posing safety concerns.Conclusion Limited quality and quantity evidence on use of psychotropic drugs and HCs suggests low concern for clinically significant interactions, though no data exist specifically for non-oral formulations of HC. Given the high frequency of use for both HCs and psychotropic drugs among reproductive-age women in the US, this review highlights a need for further research in this area.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A previously reported quality rating tool was applied to assess risk of bias.
“As there are no standard guidelines to assess the risk of bias in pharmacokinetic studies, we applied a previously reported quality rating tool [11].”
From Drug-Drug Interactions Between Glucagon-Like Peptide 1 Receptor Agonists and Oral Medications: A Systematic Review (2024) · cites this paper as [11]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & for the PRISMA Group (2009) · BMJ · doi:10.1136/bmj.b2535 · Cited by 83,823 · see citing works
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.
(2009) · PubMed Central · Cited by 44,859 · see citing works
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.6.593 · Cited by 20,391 · see citing works
PRACTICE GUIDELINE FOR THE Treatment of Patients With Major Depressive Disorder
Gelenberg, A. J., Freeman, P. B., Markowitz, J. C., Rosenbaum, J. F., Thase, M. E., Trivedi, M. H., & Rhoads, R. S. (2010) · Cited by 1,372 · see citing works
Alder, J., Fink, N., Bitzer, J., Hösli, I., & Holzgreve, W. (2007) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767050701209560 · Cited by 872 · see citing works
Jones, J., Mosher, W. D., & Daniels, K. M. (2012) · PubMed · Cited by 480 · see citing works
Mojtabai, R., & Olfson, M. (2014) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.13m08443 · Cited by 247 · see citing works
Martini, J., Knappe, S., Beesdo-Baum, K., Lieb, R., & Wittchen, H.-U. (2010) · Early Human Development · doi:10.1016/j.earlhumdev.2010.04.004 · Cited by 236 · see citing works
Halbreich, U. M. (2005) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2005.02.103 · Cited by 148 · see citing works
The risk of unintended pregnancy among young women with mental health symptoms
Hall, K. S., Kusunoki, Y., Gatny, H., & Barber, J. S. (2013) · Social Science & Medicine · doi:10.1016/j.socscimed.2013.10.037 · Cited by 112 · see citing works
Pharmacokinetic Drug Interactions Involving Vortioxetine (Lu AA21004), a Multimodal Antidepressant
Chen, G., Lee, R., Højer, A., Buchbjerg, J. K., Serenko, M., & Zhao, Z. (2013) · Clinical Drug Investigation · doi:10.1007/s40261-013-0117-6 · Cited by 103 · see citing works
Effect of oral contraceptives on triazolam, temazepam, alprazolam, and lorazepam kinetics
Stoehr, G. P., Kroboth, P. D., Juhl, R. P., Wender, D. B., Phillips, J. P., & Smith, R. B. (1984) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1984.240 · Cited by 103 · see citing works
Hall, K. S., Moreau, C., Trussell, J., & Barber, J. S. (2013) · Journal of Adolescent Health · doi:10.1016/j.jadohealth.2013.02.009 · Cited by 94 · see citing works
Mental health and access to services among US women of reproductive age
Farr, S. L., Bitsko, R. H., Hayes, D. K., & Dietz, P. M. (2010) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2010.07.007 · Cited by 93 · see citing works
Palovaara, S. (2003) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(03)00202-9 · Cited by 87 · see citing works
Depressive symptoms and Depo-Provera®
Westhoff, C. L., Truman, C. J., Kalmuss, D., Cushman, L. F., Davidson, A. R., Rulin, M. C., & Heartwell, S. (1998) · Contraception · doi:10.1016/s0010-7824(98)00024-9 · Cited by 81 · see citing works
Kornstein, S. G., Toups, M. S. P., Rush, A. J., Wisniewski, S. R., Thase, M. E., Luther, J. F., Warden, D., D, M. F. M., & Trivedi, M. H. (2013) · Journal of Women s Health · doi:10.1089/jwh.2012.3479 · Cited by 69 · see citing works
Imipramine disposition in users of oral contraceptive steroids
Abernethy, D. R., Greenblatt, D. J., & Shader, R. I. (1984) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1984.114 · Cited by 67 · see citing works
Differential Effects of Oral Contraceptive Steroids on the Metabolism of Benzodiazepines
Patwardhan, R. V., Mitchell, M. C., Johnson, R. F., & Schenker, S. (1983) · Hepatology · doi:10.1002/hep.1840030219 · Cited by 55 · see citing works
Lorazepam and oxazepam kinetics in women on low-dose oral contraceptives
Abernethy, D. R., Greenblatt, D. J., Ochs, H. R., Weyers, D., ALLEN, M. D., Harmatz, J. S., & Shader, R. I. (1983) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1983.85 · Cited by 53 · see citing works
Pharmacodynamic evaluation of the benzodiazepine–oral contraceptive interaction
Kroboth, P. D., Smith, R. B., Stoehr, G. P., et al. (1985) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1985.218 · Cited by 51 · see citing works
Enantioselective Analysis of Citalopram and Metabolites in Adolescents
Carlsson, B., Olsson, G., Reis, M., et al. (2001) · Therapeutic Drug Monitoring · doi:10.1097/00007691-200112000-00011 · Cited by 48 · see citing works
Fatal flaws in a recent meta-analysis on abortion and mental health
Steinberg, J. R., Trussell, J., Hall, K. S., et al. (2012) · Contraception · doi:10.1016/j.contraception.2012.03.012 · Cited by 47 · see citing works
Therapeutic Drug Monitoring of Escitalopram in an Outpatient Setting
Reis, M., Chermà, M. D., Björn Carlsson, A., & Bengtsson, F. (2007) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0b013e31815b3f62 · Cited by 46 · see citing works
Lurasidone drug-drug interaction studies: a comprehensive review
Chiu, Y., Ereshefsky, L., Preskorn, S., et al. (2014) · Drug metabolism and drug interactions · doi:10.1515/dmdi-2014-0005 · Cited by 43 · see citing works
Drug Interactions with Clomipramine (Anafranil)
Beaumont, G. (1973) · Journal of International Medical Research · doi:10.1177/030006057300100543 · Cited by 42 · see citing works
Reddy, M. V. (2019) · Apple Academic Press eBooks · doi:10.1201/9780429023309-5 · Cited by 41 · see citing works
Ziprasidone and the pharmacokinetics of a combined oral contraceptive
Muirhead, G. J., Harness, J. A., Holt, P. R., Oliver, S. D., & Anziano, R. (2000) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.2000.00153.x · Cited by 40 · see citing works
Sandson, N. B., Cozza, K. L., Armstrong, S. C., et al. (2007) · Psychosomatics · doi:10.1176/appi.psy.48.2.170 · Cited by 38 · see citing works
Clozapine and Oral Contraceptives: A Possible Drug Interaction
Gabbay, V., O’Dowd, M. A., Mamamtavrishvili, M., et al. (2002) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200212000-00013 · Cited by 33 · see citing works
Safety and efficacy of fluoxetine in patients who receive oral contraceptive therapy
Koke, S. C., Brown, E. B., & Miner, C. M. (2002) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2002.124939 · Cited by 30 · see citing works
Clozapine toxicity due to a multiple drug interaction: a case report
Cadeddu, G., Deidda, A., Stochino, M. E., et al. (2015) · Journal of Medical Case Reports · doi:10.1186/s13256-015-0547-2 · Cited by 30 · see citing works
Alprazolam Pharmacokinetics in Women on Low‐Dose Oral Contraceptives
Scavone, J. M., Greenblatt, D. J., Locniskar, A., et al. (1988) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1988.tb05759.x · Cited by 29 · see citing works
Reis, M., Olsson, G., Björn Carlsson, A., Lundmark, J., Dahl, M., Wålinder, J., Ahlner, J., & Bengtsson, F. (2002) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200208000-00012 · Cited by 27 · see citing works
Edelbroek, P. M., Zitman, F. G., der Klein, E. A. M. K.-V., Putten^, P. M. V., & de Wolff, F. A. (1987) · Clinica Chimica Acta · doi:10.1016/0009-8981(87)90161-6 · Cited by 21 · see citing works
Haslemo, T., Refsum, H., & Molden, E. (2010) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2010.03880.x · Cited by 18 · see citing works
Oral Contraceptives Raise Plasma Clozapine Concentrations
Bookholt, D. E., & Bogers, J. P. A. M. (2014) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000074 · Cited by 17 · see citing works
Va, J., Dk, L., & Kemp, H. (1980) · PubMed · Cited by 17 · see citing works
Reddy, M. V. (2014) · Apple Academic Press eBooks · doi:10.1201/b17560-10 · Cited by 11 · see citing works
Interaction between certain psychopharmaca and low-dose oral contraceptives.
Somos, P. (1990) · PubMed · Cited by 8 · see citing works
Dk, L., & John, V. (1980) · PubMed · Cited by 8 · see citing works
Clomipramine and oral contraceptives: an interaction study--clinical findings.
Gringras, M., Beaumont, G., & Grieve, A. P. (1980) · PubMed · Cited by 5 · see citing works
Relating plasma levels of clomipramine and clinical response.
Seldrup, J. (1980) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
U.S. Medical Eligibility Criteria for Contraceptive Use, 2016
Curtis, K. M., Tepper, N. K., Jatlaoui, T. C., Berry-Bibee, E., Horton, L. G., Zapata, L. B., Simmons, K. B., Pagano, H. P., Jamieson, D. J., & Whiteman, M. K. (2016) · MMWR. Recommendations and Reports · doi:10.15585/mmwr.rr6503a1 · Cited by 1,456 · see citing works
Self-citation(2019) · Obstetrics & Gynecology · doi:10.1097/aog.0000000000003072 · Cited by 147 · see citing works
Hormonal Contraceptives and Mood: Review of the Literature and Implications for Future Research
Robakis, T., Williams, K. E., Nutkiewicz, L., & Rasgon, N. L. (2019) · Current Psychiatry Reports · doi:10.1007/s11920-019-1034-z · Cited by 103 · see citing works
Calvarysky, B., Dotan, I., Shepshelovich, D., Leader, A., & Cohen, T. D. (2024) · Drug Safety · doi:10.1007/s40264-023-01392-3 · Cited by 97 · see citing works
- Authors
- Berry-Bibee, E. N., Kim, M.-J., Simmons, K. B., Tepper, N. K., Riley, H. E. M., Pagano, H. P., & Curtis, K. M.
- Affiliations
- United States Food and Drug Administration (US)
- Centers for Disease Control and Prevention (US)
- Venue
- Contraception
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 94
- Issue
- 6
- Pages
- 650-667
- ISSN
- 0010-7824 (ISSN-L)
- PMC
- PMC11283812
- OpenAlex
- W2486589740
- Cited by
- 52
- References
- 43
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 12 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 7 · 2018: 2 · 2017: 3 · 2016: 4
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Contraception (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (CC999999)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Keywords
- drug interactions, hormonal contraception, psychotropic drugs, selective serotonin reuptake inhibitors, tricyclic antidepressants, amitriptyline, imipramine, atypical antipsychotics, unintended pregnancy, pharmacokinetics, women of reproductive age, depression, anxiety
- MeSH terms
- Anxiety, Contraceptives, Oral, Hormonal, Depression, Drug Interactions, Female, Humans, Psychotropic Drugs, Randomized Controlled Trials as Topic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
