Depression may be an adverse effect of hormonal contraceptive use, study suggests

Antidepressant use and first diagnosis of depression peaked 6 months after starting hormonal contraceptives, and decreased with women's age for the most commonly used products.


Hormonal contraceptive use was associated with subsequent antidepressant use and diagnosis of depression among women ages 15 to 34 years living in Denmark, a recent study found.

Researchers observed these 2 outcome measures of incident depression in a population of 1,061,997 women (mean follow-up, 6.4 years) using Denmark's National Prescription Register for antidepressants and the Psychiatric Central Research Register for first discharge diagnoses of depression at all inpatient and outpatient psychiatric departments. Women who used antidepressants or received a depression diagnosis before the study period (2000 to 2013) or within the previous 5-year period were excluded, as were women receiving infertility treatment before study entry and those with diagnoses of other major psychiatric disorders, cancer, and venous thrombosis. Results were published online on Sept. 28 by JAMA Psychiatry.

Researchers defined hormonal contraceptive use as current or recent use (cessation within the past 6 months), and women in this group were 24.3 years old on average. The reference group included women who had never used hormonal contraceptives, as well as former users (mean age, 24.4 years). Current or recent users comprised 55.5% of the study population, which included 6,832,938 person-years of observation during the study period.

Compared with nonusers, users of combined oral contraceptives had a rate ratio (RR) of 1.2 (95% CI, 1.22 to 1.25) for first use of antidepressants. Progestin-only pills were associated with an RR of 1.3 (95% CI, 1.27 to 1.40); a transdermal patch (norelgestromin) was associated with an RR of 2.0 (95% CI, 1.76 to 2.18); a vaginal ring (etonogestrel) was associated with an RR of 1.6 (95% CI, 1.55 to 1.69); an implant was associated with an RR of 2.1 (95% CI, 2.01 to 2.24); a levonorgestrel intrauterine system was associated with an RR of 1.4 (95% CI, 1.31 to 1.42); and medroxyprogesterone acetate depot was associated with an RR of 2.7 (95% CI, 2.45 to 2.87). RRs for a first depression diagnosis were similar or slightly lower.

RRs for first antidepressant use and first diagnosis of depression peaked 6 months after starting hormonal contraceptives, at 1.4 (95% CI, 1.34 to 1.46) and 1.5 (95% CI, 1.36 to 1.64), respectively. RRs for first use of antidepressants decreased with women's age for the most commonly used products.

The researchers noted limitations to the study, such as potential detection bias if prescribing physicians were more aware of depressive symptoms in patients to whom they had prescribed hormonal contraceptives. In addition, antidepressants are prescribed for the treatment of conditions other than depression, and not all depressed individuals are treated with antidepressants or diagnosed at psychiatric clinics or hospitals, they noted.