Around 5% of young men between the ages of 18 and 39 are treated with antidepressants, typically selective serotonin and serotonin norepinephrine reuptake inhibitors. Not uncommonly, during the course of a perinatal psychiatry consultation, male partners will ask whether the medication they are taking could have a negative impact on the pregnancy or the developing fetus. Our information is limited, but there have been several studies examining the impact of SSRI and SNRI antidepressants on sperm quality.
In a study from 2010, Tanrikut and colleagues noted that in men treated with paroxetine (Paxil), mean DNA fragmentation levels rose from 13.8% at baseline to 30.3% while receiving treatment, and the percentage of patients with abnormal levels of DNA fragmentation (> 30%) rose from 9.7% at baseline to 50% at week 4 of treatment with paroxetine. Since these initial reports from Tanrikut et al, animal and human studies assessing the impact of other SSRIs have demonstrated, in addition to DNA fragmentation, lower testosterone levels, lower sperm motility, and increased numbers of spermatozoa with abnormal morphology.
Exactly how SSRIs affect sperm quality is not well understood. The timing of observed effects of the SSRIs on spermatozoa suggests that sperm DNA damage may occur as a consequence of the slowing of sperm transport (Tanrikut & Schlegel, 2007). Previous studies have shown that high levels of sperm DNA fragmentation (SDF) are with lower fertilization rates, impaired implantation rates and an increased incidence of miscarriage; no studies have directly studied the impact of SSRIs on male fertility.
New Data on Duloxetine
A recent study looked at the impact of the SNRI duloxetine (Cymbalta) on sperm motility and quality in a group of young men. In a double-blind, placebo-controlled, randomized clinical trial, 68 healthy male participants received duloxetine 60mg or placebo daily for 6 weeks (5 weeks treatment and 1 week taper). Abnormal DNA fragmentation during and after duloxetine administration was assessed. The researchers also measured other semen parameters and hormone levels during treatment (2 and 6 weeks) and after discontinuation (8 and 10 weeks).
Treatment with duloxetine was not associated with an increase in the proportion of participants with abnormal sperm DNA fragmentation, nor did median sperm DNA fragmentation increase after treatment with duloxetine. Compared to placebo, there were no differences in sperm concentration or motility during treatment. No clinically significant changes in hormone levels (FSH, LH, prolactin) were detected. They noted a slight decrease in testosterone levels at week 2; however, this finding was not consistent and unlikely to be clinically significant.
The current study indicates that duloxetine administered at a dose of 60 mg does not have an impact on sperm quality. They did not look at the impact of higher doses of duloxetine on sperm quality. Also important to note is that this study was performed in healthy men; the study did not include men who were taking duloxetine for a psychiatric indication. Nor did they include men with other factors which may affect sperm quality (e.g., smoking, increased BMI).
How will this finding affect our clinical practice? Will we advise men who are attempting to conceive and are taking SSRIs such as paroxetine to stop or to switch to duloxetine? Probably not. Stopping or switching to another antidepressant may increase their risk for relapse. If a man who is planning to conceive in the near future requires treatment with an SSRI or SNRI, would we be more likely to reach for duloxetine? Maybe.
Nonetheless, this type of research highlights the need to more actively include the male partner in the reproductive psychiatry consultation. As our female patients are planning for pregnancy, we ask them about their reproductive history, fertility status, and risk factors for infertility; however, do we adequately include the male partner in this discussion? It is likely that the consideration of male factors influencing fertility occurs only after the couple encounters difficulties conceiving a child.
Perhaps we should also ask about — or at least be aware of — factors affecting male fertility early on. All of the following factors have been associated with decreased sperm production or impaired quality of sperm:
- Recreational drugs: marijuana, cocaine, anabolic–androgenic steroids, opiates, and methamphetamines
- Increased body mass index (BMI)
- Psychological stress
- Advanced paternal age
- Physical factors (e.g., varicocele)
- Medical illness (e.g., epilepsy)
- Medications (e.g., calcium channel blockers, alpha-adrenergic blockers, antiretrovirals)
While a review of these factors may be beyond the scope of the typical reproductive psychiatry consultation, it is important to be aware of factors that may affect male fertility. Given the prevalence of smoking, alcohol, and cannabis use in adults of reproductive age, it is worth asking about the use of these substances in the male partner and noting that their use could affect male fertility. Most of the factors listed above are modifiable, and individuals attempting to conceive are highly motivated to make lifestyle changes in the setting of starting a family.
Ruta Nonacs, MD PhD
Beeder LA, Samplaski MK. Effect of antidepressant medications on semen parameters and male fertility. International Journal of Urology, 27(1), 39–46.
Durairajanayagam D. Lifestyle causes of male infertility. Arab J Urol. 2018 Feb 13;16(1):10-20. Free article.
Punjani N, Kang C, Flannigan R, Bach P, Altemus M, Kocsis JH, Wu A, Pierce H, Schlegel PN. Impact of duloxetine on male fertility: A randomised controlled clinical trial. Andrologia. 2021 Nov;53(10):e14207.
Tanrikut C, Schlegel PN. 2007. Antidepressant-associated changes in semen parameters. Urology 69(1):185.e5-7.
Tanrikut C, Feldman AS, Altemus M, Paduch DA, Schlegel PN. 2009. Adverse effect of paroxetine on sperm. Fertil Steril. 2010 Aug;94(3):1021-6.