Escitalopram for Sperm DNA Fragmentation

Overseen By Caroline Kang, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must not be taking: Psychotropics, Anticonvulsants, MAOIs, TCAs

Disqualifiers: Azoospermia, Psychiatric disorders, Alcohol, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether escitalopram, a medication often used for mood disorders, can improve sperm DNA quality. Researchers aim to determine if taking escitalopram daily for six weeks affects men with healthy sperm and no history of mental health issues like depression or anxiety. Participants must engage in sexual activity at least once a week during the study. As a Phase 2 trial, this research measures how well escitalopram works in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

If you are currently using psychotropic agents, anticonvulsants, sleeping pills, hormonal medications, medications to enhance sexual function, MAO inhibitors, or tricyclic antidepressants, you will need to stop taking them to participate in this trial. The protocol does not specify a washout period for these medications, but you must not have used hormonal medications in the past 3 months or MAO inhibitors and tricyclic antidepressants within 14 days.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that escitalopram, a medication commonly used to treat depression, might affect sperm health. Some studies have found that medications like escitalopram can alter sperm shape, movement, and DNA. For instance, patients taking these medications showed more damage to sperm DNA compared to those not taking them. In one study, about 43% of sperm DNA was damaged in patients on these medications, while only 21% was damaged in those who weren't.

While this suggests possible risks to sperm health, it's important to remember that the FDA has approved escitalopram for treating depression, indicating it is generally considered safe for use. However, its specific effects on sperm are still under investigation. Discussing any concerns with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for sperm DNA fragmentation, which often involve lifestyle changes, antioxidants, or hormonal therapy, Escitalopram offers a novel approach. Researchers are excited about Escitalopram because it is primarily known as an antidepressant that selectively inhibits serotonin reuptake, which could offer unique benefits for sperm quality. Its potential to improve sperm DNA integrity through a different mechanism than existing treatments opens new possibilities for addressing male infertility.

What evidence suggests that escitalopram might be an effective treatment for sperm DNA fragmentation?

This trial will compare the effects of escitalopram, an antidepressant, with a placebo on sperm DNA fragmentation. Research has shown that escitalopram can affect sperm quality. Studies suggest that antidepressants, including escitalopram, may alter sperm shape and movement and can damage sperm DNA. Some findings report increased sperm DNA damage after using these medications. However, the specific effects of escitalopram on sperm and fertility remain unclear. Further research is needed to determine whether escitalopram might help or harm sperm health. ^{1 2 3 4 6}

Who Is on the Research Team?

Jonathan Gal, MD

Principal Investigator

Weill Medical College of Cornell University

Peter Schlegel, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

Men with normal or slightly low sperm counts who are not currently trying to conceive and have no psychiatric disorders, liver disease, family history of bipolar disorder or suicide. Participants must be able to engage in weekly sexual activity and provide semen samples throughout the 10-week study.

Inclusion Criteria

I am willing to be sexually active weekly for 10 weeks.

Normal semen analyses, or semen analyses with at least 5 million sperm

Normal TUNEL value (<7%)

Exclusion Criteria

I haven't taken MAO inhibitors or tricyclic antidepressants in the last 14 days.

I have a liver condition.

Alcohol consumption greater than 2oz/day

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily escitalopram or placebo for 6 weeks

6 weeks

1 visit (in-person) at baseline, 1 visit (in-person) at 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) at 10 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Escitalopram
• Placebo

Trial Overview The trial is testing if Escitalopram affects sperm DNA quality over a period of 6 weeks compared to a placebo. It's a double-blind study, meaning neither participants nor researchers know who gets the real drug. Measurements include hormone levels, semen analysis, and sexual function.

How Is the Trial Designed?

Group I: Escitalopram Experimental Treatment 1 Intervention

10mg by mouth daily for 6 weeks

Group II: Placebo Placebo Group 1 Intervention

Matched placebo control by mouth for 6 weeks.

Escitalopram is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Lexapro for:

• Major depressive disorder
• Generalized anxiety disorder

Approved in European Union as Cipralex for:

• Major depressive episodes
• Generalized anxiety disorder
• Social anxiety disorder
• Panic disorder with or without agoraphobia
• Obsessive-compulsive disorder

Approved in Canada as Cipralex for:

• Major depressive disorder
• Generalized anxiety disorder
• Social anxiety disorder

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Published Research Related to This Trial

Psychotropic drugs, particularly SSRIs, can negatively impact sexual function and semen quality in men, with SSRIs linked to increased sperm DNA fragmentation and ejaculatory latency.

While some medications like NDRIs and SARIs show minimal effects on prolactin levels and sexual side effects, there is a significant knowledge gap regarding the impact of antipsychotics and anticonvulsants on semen quality, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychotropics and Male Reproduction. Drobnis, EZ., Nangia, AK.[2022]

Escitalopram, the S-enantiomer of citalopram, is the most selective selective serotonin reuptake inhibitor (SSRI) and has shown approximately twice the potency of its racemic counterpart in treating depression.

Clinical trials indicate that escitalopram not only has superior efficacy compared to citalopram but also maintains an excellent safety profile, making it a strong candidate for first-line treatment in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Escitalopram: a second-generation SSRI. Owens, MJ., Rosenbaum, JF.[2019]

In a study of 74 depressed men on selective serotonin reuptake inhibitors (SSRIs), significant reductions in total sperm count and motility were observed compared to 44 healthy controls, indicating that SSRIs may negatively affect semen quality.

Patients on SSRIs showed increased sperm DNA fragmentation, with 43.2% of their DNA being denatured compared to 21.4% in controls, suggesting potential damage to sperm DNA integrity associated with SSRI treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sperm DNA damage and semen quality impairment after treatment with selective serotonin reuptake inhibitors detected using semen analysis and sperm chromatin structure assay. Safarinejad, MR.[2023]

In a clinical trial involving 68 healthy males, duloxetine did not significantly affect sperm DNA fragmentation or semen parameters after 6 weeks of treatment, suggesting it does not harm male fertility.

The study indicates that duloxetine, a serotonin and norepinephrine reuptake inhibitor, may be a safe antidepressant option for men who are concerned about maintaining their fertility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of duloxetine on male fertility: A randomised controlled clinical trial. Punjani, N., Kang, C., Flannigan, R., et al.[2022]

Three cohort studies involving over 100 patients revealed that exposure to SSRIs for as little as 3 months can lead to significant changes in semen quality, including reduced sperm concentration and motility, and increased sperm DNA fragmentation.

SSRIs may have potential endocrine-disrupting effects, which could impact male fertility, highlighting the need for healthcare providers to inform male patients about these risks, especially those planning to father children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semen abnormalities with SSRI antidepressants. [2022]

Long-term administration of citalopram at doses of 12 and 24 mg/kg/day in male mice resulted in significant increases in sperm DNA strand breaks and aberrant primary spermatocytes, indicating potential genotoxic effects on germ cells.

The study suggests that male patients taking citalopram may face a higher risk of abnormal reproductive outcomes, particularly if they are of reproductive age, highlighting a safety concern regarding its long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Citalopram at the recommended human doses after long-term treatment is genotoxic for male germ cell. Attia, SM., Bakheet, SA.[2013]

A systematic review of 4 studies involving 222 male participants found that selective serotonin reuptake inhibitors (SSRIs) significantly reduce sperm quality, including normal sperm morphology, sperm concentration, and sperm motility within just 3 months of use.

SSRIs also increase sperm DNA fragmentation, indicating potential long-term effects on male fertility, although they do not significantly affect semen volume.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of SSRIs on Semen quality: A systematic review and meta-analysis. Xu, J., He, K., Zhou, Y., et al.[2022]

In a study involving 506 patients with severe depression, escitalopram demonstrated significantly greater efficacy than citalopram, with a mean change in the Montgomery-Asberg Depression Rating Scale (MADRS) score of -17.3 compared to -13.8 for citalopram (p=0.003).

Escitalopram also showed higher response rates (56% vs 41% for citalopram, p=0.007) and a faster onset of action, indicating it may be a more effective first-line treatment for major depressive disorder (MDD) in severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Escitalopram is more effective than citalopram for the treatment of severe major depressive disorder]. Azorin, JM., Llorca, PM., Despiegel, N., et al.[2022]

Citations

1. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/43/NCT03527043/Prot_SAP_000.pdf

Impact of Escitalopram on Sperm DNA Fragmentation NCT ... The effects of escitalopram on sperm and fertility are largely unknown, but limited data available is mentioned above.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9519136/

The effect of SSRIs on Semen quality: A systematic review ... The results indicate that SSRIs can affect sperm morphology, sperm concentration, sperm motility and sperm DNA integrity without a measurable ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022534708018375

Sperm DNA Damage and Semen Quality Impairment After ... Patients receiving SSRIs had statistically significant impairment in all semen parameters and increased sperm DNA damage.

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/iju.14111

Effect of antidepressant medications on semen parameters ... In addition, the number of men having elevated sperm DNA fragmentation of >30% increased from 10% at baseline to 50% post-treatment (odds ratio ...

5. trialx.com trialx.com/clinical-trials/listings/239457/impact-of-escitalopram-on-sperm-dna-fragmentation/?&geo_lat=40.7928&geo_lng=-73.7767&radius=10&place=Bayside&user_country=United%20States

Impact of Escitalopram on Sperm DNA Fragmentation Significant evidence exists that they may be harmful for paternal fertility potential in both animal and human studies. However, high quality ...

6. withpower.com withpower.com/trial/phase-3-infertility-9-2017-2cdbf

Escitalopram for Sperm DNA Fragmentation Patients on SSRIs showed increased sperm DNA fragmentation, with 43.2% of their DNA being denatured compared to 21.4% in controls, suggesting potential damage ...