Selective serotonin reuptake inhibitors, or SSRI’s, are popular drugs that treat depression by increasing the amount of a neurotransmitter called serotonin in the brain.
But when a common SSRI known as sertraline is taken by women during pregnancy, there is a small risk that it can have adverse side effects on children’s development.
Now a Tufts team, including three undergraduates, have found that the birth defects might result from sertraline directly damaging a cell’s genetic information, or DNA – and that one potential way to counter this effect is with antioxidants such as vitamin C. Their results were published recently in Scientific Reports.
To study the issue, Michael Levin, A92, Vannevar Bush Professor of Biology, and Mitch McVey, a professor of molecular biology who specializes in fruit fly genetics and DNA repair, worked with undergraduates Catherine Donlon, A16, Arpita Jajoo, A19, and Sarah Shnayder, A20.
Donlon spearheaded the project in McVey’s lab as part of her senior honors thesis. To see if sertraline affected baby flies like it does children, Donlon raised thousands of fruit flies in the lab, feeding the mothers sertraline-laced sugar water.
When Donlon didn’t see a clear effect on the baby flies, she instead tried feeding sertraline – which is better known under its brand name Zoloft – to the developing fruit fly larvae.
Although fruit fly larvae do not develop inside their mothers, they somewhat resemble human embryos in that their organs and bodies continue to develop over time.
Based on what’s known about some of the developmental effects seen in children of mothers who take sertraline for mental disorders, Donlon hypothesized that sertraline-eating larvae would develop more slowly than other larvae.
But in fact almost half of the larvae that consumed sertraline died before reaching the final stage in their development. McVey was struck by Donlon’s results.
“What surprised me the most is that people have looked at the effects of sertraline in human cell culture and in mice in the past, and they haven’t seen any real toxicity,” he said.
Sertraline “didn’t seem to have much effect on the mice, which is one reason that this drug has been on the market for so long, and it’s been so successful.”
“At the same time, serotonin has been shown to be a key player in embryonic patterning in other model systems; this is why other SSRIs are known to cause birth defects in vertebrates,” Levin said.
“Cells were using this neurotransmitter molecule to communicate about how to make an embryo long before neurons evolved.”
McVey and Levin’s team then sought to determine how sertraline killed the larvae. Was it that the larvae died because of sertraline’s effects on serotonin levels, or because of some innate toxicity of the drug?
Jajoo repeated Donlon’s experiment, but also included some fruit fly larvae that lack the protein responsible for transporting serotonin back into cells. Without this protein, serotonin levels should be higher than normal outside of cells.
If those flies developed slowly, then serotonin might be to blame for the deaths. But if sertraline-eating larvae develop even slower than these flies, then the drug itself might be directly damaging cells’ DNA – which is exactly what Jajoo found.
To confirm that the drug directly damages the flies’ DNA, Jajoo bathed developing wing tissues in sertraline and used a staining technique that visualizes the number of double-stranded breaks in the DNA.
Wing tissues bathed in sertraline showed three times the normal number of double-stranded DNA breaks, suggesting that sertraline might cause birth defects by directly damaging the genetic code of developing embryos.
Donlon, now a medical student at New York Medical College, put the use of the drug by expectant mothers in perspective.
“I think it’s great to understand the mechanism of how things like sertraline work, but it’s also really important to understand the reason why medications are prescribed in the first place,” she said.
Jajoo, also a medical student now, echoed Donlon’s view. “You have to think about two patients,” she said. “You have to think about both the developing fetus and the mother, and if the mother needs this SSRI for her wellbeing, then instead of saying, “OK, this is damaging, take it away,” it would be awesome if it was, “OK, this is damaging, we know how, let’s fix it.'”
The team approached their next experiment with this mindset. Levin had a hunch that the damage to the DNA might be caused by reactive oxygen species, an unstable molecule containing oxygen that readily reacts with other molecules and that can be dangerous to cells if not balanced within the body.
“There was this great breakthrough moment,” said Jajoo, “where I was sitting in a meeting with both Mitch [McVey] and Mike [Levin] and Mike said, “Well, if it’s oxidative, can we just throw an antioxidant at it?” And we all kind of laughed and then we were like, “Wait, can we?'”
They could and did. The team fed fruit fly larvae both sertraline and vitamin C, a powerful antioxidant, and saw that almost all of the larvae survived. Additionally, they found significantly fewer double-stranded DNA breaks. This supported the idea that the sertraline-induced DNA damage results from reactive oxygen species.
But they didn’t definitively show that, McVey said. “It would be nice to know how sertraline is interacting with DNA—if it is—and causing damage. Or is it an indirect effect?”
McVey and Levin hope to pursue these questions in the future; according to McVey, they’re just waiting for the “right student” to work on the project.
Antidepressants are one of the most commonly used therapeutic drug classes in the USA. While the majority of these medications are taken to treat depression, antidepressants can also be taken to treat other conditions, such as anxiety disorders. The major classes of these are SSRIs, SNRIs, NDRIs, TCAs, MAOIs and atypical antidepressants. Each of these have slightly different mechanisms of action, and therefore can affect sperm in different ways.
According to the National Health and Nutrition Examination Survey, 8.6% of males between the ages of 12 and 18 in the USA took antidepressants between 2011 and 2014.1 The number of people taking these medications has increased nearly 65% over a 15‐year time frame, from 7.7% in 1999–2002 to 12.7% in 2011–2014.
Although females are more likely to use these mediations, males have shown a parallel rise in their antidepressant use. Antidepressant use increases with age, from 3.4% among persons aged 12–19 years to 19.1% among persons aged ≥60 years.
In addition, these medications are typically taken long term, and between 2011 and 2014, 68.0% of persons aged ≥12 years who took antidepressant medications had been taking these for ≥2 years, and 25% had been taking them for ≥10 years.
There is limited information on the frequency of antidepressant use globally. The Organization for Economic Co‐operation and Development has examined this to some degree.
Countries with the highest rates of antidepressant use are the USA (110 per 1000 people), Iceland (106 per 1000 people), Australia (89 per 1000 people), Canada (86 per 1000 people) and Denmark (85 per 1000 people). Countries with the lowest reported antidepressant use are Korea (13 per 1000 people), Chile (13 per 1000 people), Estonia (18 per 1000 people), Hungary (27 per 1000 people) and the Slovak Republic (31 per 1000 people).2 For Japan specifically, although large epidemiological studies are lacking, it is estimated that up to 6 million Japanese suffer from depression, similar to that seen in Western countries.3
All classes of antidepressants are known to be associated with some degree of sexual dysfunction in both men and women. In men, the most notable sexual side‐effects can include impaired libido, erectile dysfunction, delayed ejaculation or anejaculation.
The effects of antidepressant medications on semen parameters have been less thoroughly studied, although data do exist for some of the medications in each of the classes of antidepressants. We review all available data (in vitro, animal and human studies) regarding the use of antidepressants on semen parameters and male fertility (Table 1).Table 1. Studies carried out on different antidepressant classes
|Antidepressant class||In vitro studies||Case studies||Animal studies||Human studies|
|SSRIs||Kumar et al.6||–||Bataineh and Daradka7Alzahrani8Galal et al.9Sakr et al.10Atli et al.11Attia and Bakheet12Ilgin et al.13Ayala et al.14Vieira et al.15||Tanrikut and Schlegel16Elnazer and Baldwin18Tanrikut et al.19Akasheh et al.20Koyuncu et al.21Safarinejad22Relwani et al.23|
|SNRIs||Bandegi et al.24||–||Bandegi et al.24||–|
|NDRIs||–||–||Urra et al.25Cavariani et al.26Fazelipour et al.28Cansu et al.29Adriani et al.30Bellentani et al.31||–|
|TCAs||Levin et al.32||–||Bandegi et al.24Chowdary and Rao34Hassanane et al.35||Levin et al.32Padrón and Nodarse33|
|MAOIs||–||–||Kalász et al.36Mihalik et al.37||–|
|Atypical antidepressants||Cassidy and Pearson39||Elnazer and Baldwin18||Ilgin et al.38El‐Sisi et al.40||–|
SSRIs act by inhibiting the reuptake of serotonin, and include citalopram, escitalopram, fluvoxamine, paroxetine, fluoxetine and sertraline. These medications are currently considered first line for the treatment of depression and anxiety disorders.
However, SSRIs in particular are known to be associated with significant sexual side‐effects, including decreased libido, increased ejaculation latency, alteration of circulating hormones and erectile dyfunction.4, 5
Studies estimate that 25–73% of people treated with an SSRI will experience some type of sexual dysfunction, higher than that of other antidepressants.4 Studies looking at the impact of these medications on male reproduction and semen parameters are not as robust, but there are some available data.
This is the class of antidepressants with the most available data for their effects on semen parameters and male fertility (Table 2).Table 2. SSRI effects on semen and other fertility parameters
|Drug||In vivo effects on semen parameters||Other effects on fertility|
|Fluoxetine||Rats: Decreased spermatogenesis, sperm density and motility||Rats: Decreased pregnancy and implantation rates, decreased reproductive organ weight|
|Fluvoxamine||Rats: Decreased sperm concentration and motility, increased abnormal forms||Rats: Oxidative stress and apoptosis in testes, decreased FSH, LH, testosterone and estrogen|
|Sertraline||Human case study: Decreased sperm concentration and motility||Rats: Testicular degeneration, oxidative stress|
|Human prospective: Decreased sperm count, increased abnormal morphology and DNA fragmentation|
|Rats: Increased DNA damage and abnormal forms, decreased sperm count|
|Citalopram||Human case study: Decreased sperm count and motility, increased abnormal morphology||Rats: Decreased seminal vesicle mass, decreased volume of seminiferous tubules|
|Rats: Increased DNA strand breaks and oxidative damage, increased abnormal forms|
|Paroxetine||Human prospective: Increase in DNA fragmentation||–|
|Escitalopram||Human prospective: Decreased sperm concentration and motility, increased abnormal morphology||–|
In vitro studies
There is a single in vitro study investigating SSRIs and human sperm. Kumar et al. incubated human semen with varying doses of paroxetine, fluoxetine, sertraline, citalopram and fluvoxamine in vitro. All SSRIs showed some degree of spermicidal activity, whereas serotonin showed no negative effect on sperm counts. Fluoxetine, which showed the highest spermicidal activity, had a minimal effective concentration comparable to nonoxynol‐9, a contraceptive utilized for its spermicidal properties.6
Human data consistently support an association between male infertility (semen parameters and sperm DNA fragmentation) and SSRI use. In 2007, Tanrikut and Schlegel described cases of oligospermia, impaired motility and abnormal morphology in two patients taking SSRIs for depression.
The first patient presented on citalopram with “marked oligospermia and 1% motility.” Semen analysis 1 month after citalopram discontinuation showed a marked improvement in all parameters to within the normal range. Bupropion was started for depression shortly thereafter, and a semen analysis while on bupropion again showed a decrease in sperm concentration to 21 million/mL with 10% motility.
After two failed in vitro fertilization attempts, the patient was reassessed (still on bupropion). His DNA fragmentation (tested by the sperm chromatin structural assay) was 76%. He was weaned from the bupropion and his follow‐up semen analysis 1 month after bupropion discontinuation showed a normal sperm concentration of 41 million/mL with 75% motility.
A second semen analysis carried out 2 months after bupropion discontinuation showed normal sperm concentration and motility. A similar pattern (impaired semen parameters on sertraline [sperm concentration of 20 000 with 0% motility]), with dramatic improvement after SSRI discontinuation (3 months after discontinuation 40 million motile sperm) was seen for the second patient described taking sertraline.16
Human spermatogenesis takes 72 days, and therefore this marked improvement within weeks of antidepressant discontinuation suggests that SSRIs might exert their effects on post‐testicular processes rather than spermatogenesis itself.17 Similarly, Elnazer and Baldwin described a patient with markedly improved sperm concentration, progressive motility and morphology after discontinuation of citalopram.18
In a subsequent prospective study, Tanrikut et al. examined the effects of paroxetine on semen parameters and DNA fragmentation in 35 healthy male volunteers with normal baseline semen parameters and DNA fragmentation (measured by the TUNEL assay).
Study participants (mean age 34 years, range 19–58 years) were treated with therapeutic paroxetine for 5 weeks. Semen parameters and sperm DNA fragmentation were tested before treatment and again post‐treatment after a 1‐month washout period. Use of paroxetine was associated with a significant increase in DNA fragmentation, from 14% at baseline to 30% post‐treatment.
In addition, the number of men having elevated sperm DNA fragmentation of >30% increased from 10% at baseline to 50% post‐treatment (odds ratio 9, confidence interval 2.3–38). In contrast to some other studies, these authors did not identify a change in semen parameters with SSRI use.19
This suggests that although raw semen parameters might be affected by SSRI use, sperm DNA fragmentation might also be affected even in the absence of changes in semen parameters and could represent an alternative means for impaired male reproductive potential.
Prospective data have also supported a relationship between SSRI use and markers of male infertility. In a randomized, single‐blinded clinical trial, 60 men were treated for primary premature ejaculation with either sertraline or non‐pharmacological behavioral therapy.
The sertraline group was treated with sertraline 25 mg/day for 1 week, followed by 50 mg/day for 3 months. Both sperm concentration (reduction by 105/mL) and percent normal morphology were significantly decreased in the sertraline group versus controls. DNA fragmentation (sperm chromatin dispersion method) was also increased in the treatment group (31% vs 16%).20
Another prospective study by Koyuncu et al. showed decreased sperm concentration (26.4 × 106/mL vs 68.9 × 106/mL), motility (23.4% vs 58.2%) and morphology (23.4% vs 58.2%) after 3 months of exposure to escitalopram for the treatment of premature ejaculation.21
Other factors, including duration of SSRI use and BMI, might synergistically adversely affect semen parameters. One cross‐sectional study compared semen parameters and sperm DNA fragmentation in men taking SSRIs versus those of healthy men, and also included an evaluation of the duration of antidepressant use.
Men taking SSRIs were found to have significantly lower sperm counts (61 million vs 184 million), motility (49% vs 66%) and normal morphology (8% vs 20%), as well as significantly increased amounts of fragmented sperm DNA versus controls (43% vs 21%).
All differences in semen parameters and sperm DNA fragmentation correlated with the duration of antidepressant use (6–12 months vs 1–2 years), although no differences were observed between specific antidepressants within the SSRI class.22 Another study of 530 men aged 18–50 years examining the effect of BMI found that use of combination SSRIs was associated with a significant decrease in sperm motility, independent of BMI.23
In vitro, animal and human studies all showed a decline in semen quality with SSRI use, as manifested by both impaired semen parameters and increased DNA fragmentation rates. The duration of recovery (<73 days, the time required for spermatogenesis) to baseline semen parameters and DNA fragmentation suggests that these effects might be due to some type of post‐testicular process.
Given the wide prevalence of the use of this class of medications, there is a clear need for further large‐scale, randomized, placebo‐controlled trials to further characterize the role of SSRIs in infertility, and their effect on semen parameters and other markers of male fertility.
SNRIs and NDRIs
SNRIs exert their effects by inhibiting the reabsorption of both serotonin and norepinephrine. This class of medications includes desvenlafaxine, duloxetine, levomilnacipran and venlafaxine.
The prevalence of sexual dysfunction is 58–70% in patients treated with SNRIs,4 in general slightly less than that seen for SSRIs. There has only been a single study investigating the effects of any of these medications on semen parameters (Table 3). This group examined 40 adult male mice given oral venlafaxine (2 mg/kg) or venlafaxine (2 mg/kg) plus vitamin C (10 mg/kg) for 35 days.
Mice treated with venlafaxine alone had better sperm morphology (58.50% vs 43.71%), non‐progressive motility (25.50% vs 16.25%) and sperm viability (80.25% vs 64.62%) compared with controls. This effect is thought to be a result of the anti‐oxidant properties of venlafaxine in protecting against lipid peroxidation. There were no significant differences between semen parameters in mice treated with venlafaxine alone and those treated with combination venlafaxine and ascorbic acid.24
Table 3. Non‐SSRI antidepressant effects on semen and other fertility parameters
|Drug||In vivo effects on semen parameters||Other effects on fertility|
|Venlafaxine||Human prospective: Improved normal morphology and sperm viability, increased non‐progressive motility||–|
|Bupropion||Rats: Decreased motility at high doses (30 mg/kg)||Rats: Increased epididymal duct contractility|
|Methylphenidate||Rats: Increased abnormal sperm tail morphology; increased spermatogonia; reduced round spermatids; increased sperm count||Rats: Increased testicular interstitial tissue; decreased germinal epithelium thickness, increased gonadotropins; decreased testicular weight, increase in apoptosis; increased testicular weight|
|Sibutramine||Rats: Decreased sperm number in epididymis, decreased transit time within epididymis||Rats: Decreased reproductive organ weight|
|Desipramine||Human: No change in sperm count or motility||–|
|Amitriptyline||Human prospective: Increased ejaculate volume, sperm count and normal morphology; decreased sperm concentration and viability; decreased sperm count and normal forms||Human prospective: Increased germ cell mutations|
|Selegiline||Rats: Increased sperm count and viability||Rats: Increase in testis mass|
|Trazodone||Rats: Decreased sperm concentration, motility and normal morphology, increased DNA damage||–|
|Mirtazapine||Rats: Protective effect against nitrofurazone‐induced decrease in sperm count and viability||–|
|Agomelatine||Human case study: No effect on semen parameters||–|
NDRIs act by blocking the reuptake of norepinephrine and dopamine from the synaptic terminal, thereby increasing their bioavailability.
This class includes bupropion, dexmethylphenidate, diphenylprolinol, ethylphenidate, methylenedioxypyrovalerone, methylphenidate, pipradrol, prolintane and sibutramine. In general, the limited available data for these medications show varied effects on semen parameters (Table 3).
Bupropion is commonly used in combination with other medications in the treatment of depression, as well as for smoking cessation. Although the role of dopamine in reproductive physiology has not been clearly established, there are limited data implicating some role in male reproductive function. Urra et al. first identified the presence of functional dopamine transporters in equine sperm. In the present study, high levels of dopamine were associated with decreased total and progressive sperm motility, and this effect was partially reversed by the addition of bupropion. Blocking the dopamine transporter reduced uptake of a dopamine analog, thereby decreasing accumulation of the catecholamine in equine sperm.25 Another study evaluated the effects of bupropion on semen parameters and epididymal duct contractility in rats. At lower doses (15 mg/kg), bupropion increased epididymal duct contractility, but had no effect on semen parameters. At higher doses (30 mg/kg), the drug was shown to impair sperm motility.26
Methylphenidate is a psychostimulant that inhibits norepinephrine and dopamine reuptake. It is currently most commonly used in the treatment of attention‐deficit/hyperactivity disorder in children and adolescents. In the past it was used as an antidepressant, and there are some conflicting data on its effect on semen parameters. Motagnini et al. studied the effects of methylphenidate administration on rats during childhood and young adult development. An increase in abnormal sperm tail morphology was observed, as well as an increase in testicular interstitial tissue in treated animals.27 A different rat study found that treatment with methylphenidate was associated with decreased germinal epithelium thickness, as well as an increase in the number of spermatogonia, likely secondary to increases in serum gonadotropin levels.28 Finally, a rat study by Cansu et al. showed a dose‐dependent association between 90‐day exposure to methylphenidate and reduced numbers of round spermatids, decreased testicular weight, and an increase in apoptosis (TUNEL method) and expression of p53.29 Conversely, Adriani et al. found that adolescent rats exposed to methylphenidate had increased testicular weights and increased sperm count as adults.30 These data are conflicting, and there are no human data, making it difficult to truly know the effect of methylphenidate on semen parameters and male fertility.
Sibutramine, initially developed for use in the treatment of depression, is a monoamine reuptake inhibitor commonly used today for weight loss. There are no human studies for sibutramine, and only a single animal study. Bellentani et al. found that exposure to 10 mg/kg of sibutramine for 28 days decreased weights of reproductive organs in male rats, including the ventral prostate and epididymis, although there were no histological changes noted in these organs. The sperm number within the epididymis (180.98 × 106/organ vs 276.16 × 106/organ) and transit time within the epididymis (4.73 days vs 7.85 days) were also significantly decreased. There was no change in spermatid number within testes, daily sperm production, sperm motility or morphology between groups.31
There is a clear lack of data for many of these medications. No studies exist for duloxetine, desvenlafaxine, levomilnacipran, dexmethylphenidate, diphenylprolinol, ethylphenidate, methylenedioxypyrovalerone, pipradrol or prolintane. Scant data exist for venlafaxine, bupropion, methylphenidate and sibutramine. No prospective clinical studies have yet been carried out exploring the effects of SNRIs and NDRIs on semen quality. Given the contradictory results found in preliminary animal studies, there is a clear need for additional research in this area.
TCAs, including amitriptyline, nortriptyline, amoxapine, desipramine, doxepin, imipramine, protriptyline and trimipramine, were one of the earliest medications used to treat depression. However, they are generally no longer used as first‐line medications because of significant side‐effect profiles. The estimated prevalence of sexual dysfunction in men and women taking TCAs is comparatively low, at approximately 30%.4 Evidence regarding the effects of TCAs on semen quality is scant (Table 3). There is a small number of studies on desipramine and amitriptyline, but no studies on nortriptyline, amoxapine, doxepin, imipramine, protriptyline or trimipramine.
A 1981 study by Levin et al. described both in vitro and clinical studies examining the effect of desipramine on semen parameters. In vitro, desipramine was associated with dose‐dependent inhibition of sperm motility. However, in vivo clinical evaluation found no difference in sperm count or motility between treatment and control groups. Treatment with desipramine was associated with decreased sperm viability (defined as the percentage of motile spermatozoa, no true viability testing was carried out). Other semen parameters did not significantly differ between treatment and control groups.32
There have been four studies examining amitriptyline, yielding conflicting results. A small study on the effects of amitriptyline in 20 infertile men with oligospermia found increased ejaculate volume, sperm count and normal morphology after treatment with amitriptyline. Sperm count was increased in 50% of patients, and motility was increased in 35% of patients.33 In contrast, Bandegi et al. found negative effects of amitriptyline on semen parameters in rats treated with amitriptyline alone versus amitriptyline and ascorbic acid. Rats treated with amitriptyline alone had lower sperm concentration (18.11 million vs 22.41 million) and viability (31.25% vs 64.62%) compared with controls. These results were also seen when comparing the group receiving amitriptyline plus ascorbic acid and controls, and the addition of ascorbic acid did not seem to mitigate this effect.24 Two studies suggest that amitriptyline has a mutagenic effect on sperm. A study by Chowdary and Rao showed mutagenic effects of amitriptyline in germ cells of mice treated with various oral doses of the antidepressant.34 Similar results were obtained in an animal study in which amitriptyline was found to increase chromosome abnormalities, and decrease sperm count and normal morphology.35
MAOIs are typically reserved for patients who have failed other first‐line medications for the treatment of depression. Medications belonging to this class include selegiline, isocarboxazid, phenelzine and tranylcypromine. Approximately 40% of male and female patients taking MAOIs will experience some degree of sexual dysfunction.4 Data on semen parameters are scant (Table 3). There have been two rat studies examining the effects of selegiline, but no studies examining the effects of other MAOIs, including isocarboxazid, phenelzine and tranylcypromine, on semen parameters or other markers of male fertility.
Selegiline, used to treat major depressive disorder and parkinsonism, might actually have a favorable effect on male fertility. A small rat study found an increase in testis mass, sperm number and viability (defined as the ratio of live to dead sperm) in rats treated with oral selegiline for 4 weeks.36 These findings were corroborated in a study of rats treated with intraperitoneal selegiline. Treated rats had significantly higher sperm counts (137.73 × 106/mL vs 115.09 × 106/mL on semen analysis) than those receiving intraperitoneal saline.37 The mechanism for this increase in sperm counts and viability is unclear.
Atypical antidepressants are those that act by mechanisms separate from those discussed above. These medications include mirtazapine, trazodone, nefazodone, tianeptine, agomelatine, vilazodone and vortioxetine. There are limited data regarding the effects of these medications on fertility through semen parameters, although the available data do suggest a negative effect on semen quality (Table 3).
One study of rats receiving vehicle (control), 5, 10 or 20 mg/kg/day of trazodone for 28 consecutive days found decreased sperm concentration (4.68 × 106/mL, 3.04 × 106/mL, 2.84 × 106/mL and 2.68 × 106/mL, respectively), sperm motility (86.49%, 80.06%, 78.85% and 76.23%, respectively) and normal morphology (18.00%, 28.90%, 31.20% and 37.08% abnormal forms, respectively), as well as increased DNA damage in treated rats. Increased malondialdehyde levels suggested that oxidative stress contributed to the testicular toxicity in these animals.38 Similarly, Cassidy and Pearson showed that trazodone had an inhibitory effect on motility in in vitro samples of human sperm.39
Mirtazapine has been shown in one study to have a protective effect against oxidative stress and testicular damage. In that study, testicular damage in rats was induced by administration of nitrofurazone. Rats exposed prophylactically to mirtazapine 1 week before the initiation of nitrofurazone had a significantly less pronounced decline in sperm count and viability than those receiving only nitrofurazone, as well as decreased indicators of oxidative damage.40
One case study suggested that agomelatine (vs citalopram) does not negatively impact semen quality (at least in one patient). Elnazer and Baldwin described a case of decreased sperm concentration, motility, progressive motility and normal morphology in a patient treated with citalopram for mixed depression and anxiety. These effects resolved after withdrawal of citalopram. The patient was subsequently treated with agomelatine, which was not associated with a decline in semen parameters.18
There have been no studies to date regarding the effects of nefazodone, tianeptine, vilazodone or vortioxetine on semen parameters or other markers for male fertility.
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More information: Arpita Jajoo et al. Sertraline induces DNA damage and cellular toxicity in Drosophila that can be ameliorated by antioxidants, Scientific Reports (2020). DOI: 10.1038/s41598-020-61362-y