Antidepressants associated with decreased fertility

1. Antidepressant use during a given menstrual cycle was associated with decreased fecundability during that cycle.

2. History of anxiety or depression was not independently associated with decreased fertility.

Evidence Rating Level: 2 (Good)

Study Rundown: Antidepressants are one of the most frequently prescribed classes of drugs in the United States. Overall, the benefits of treating major depression in pregnancy greatly outweigh the risks. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used antidepressants in pregnancy and are associated with a low risk of teratogenicity, with the exception of paroxetine. While the effects of antidepressants in pregnancy has been studied, much less is known about the impact of antidepressants on fertility. Animal and human models suggest that antidepressants increase the levels of allopregnanolone, a neuroactive substance that may alter normal hypothalamic-pituitary axis function. Prior studies demonstrated that allopregnanolone was associated with reduced levels of FSH and LH and decreased likelihood of ovulation. In the present work, authors evaluated their hypothesis that antidepressant use has a negative impact on fecundability. Their secondary analysis supported this hypothesis and found that antidepressant use during a given menstrual cycle was associated with reduced likelihood of conception during that cycle.

Strengths of the study included prospective design, inclusion of known confounders, and detailed daily data collection. However, caution is warranted when interpreting findings. Because depression itself can be associated with decreased libido or isolating behaviors, a comparison group of healthy woman may bias results away from the null. The most well-designed studies to responsibly address the impact of medical treatment of depression would compare outcomes in women with depression who are currently on medication to women with depression not currently on medication. Additional limitations were poor generalizability to other populations and lack of evaluation of the indication for and dose of antidepressant medications. Further prospective studies evaluating the impact of depression, medication and specifically assessing dose-response relationships are needed to guide recommendations for antidepressant use in women attempting pregnancy.

Click to read the study in AJOG

Relevant Reading: Allopregnanolone, a GABA_A receptor agonist, decreases gonadotropin levels in women: a preliminary study

In-Depth [prospective cohort]: This secondary analysis evaluated the likelihood of conception among women aged 30 to 44 years who used antidepressant medications (n = 92) and those who did not (n = 865). The primary outcome of interest was a positive pregnancy test.

The rate of antidepressant use at any point during the study period was 9.6%. Baseline use of antidepressants was not associated with differences in fecundability overall. However, after adjustment for a history of anxiety and depression, antidepressant use during a given menstrual cycle was associated with decreased fecundability during that cycle (FR 0.66, CI 0.45-0.97).

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