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

75 Participants Needed

Trial Summary

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 the drug Escitalopram effective for improving sperm DNA fragmentation?

Research suggests that selective serotonin reuptake inhibitors (SSRIs), including Escitalopram, may negatively affect semen quality, including increasing sperm DNA fragmentation. Therefore, Escitalopram might not be effective for improving sperm DNA fragmentation. ^{1 2 3 4 5}

Is escitalopram safe for human use, particularly regarding male fertility?

Escitalopram, like other SSRIs, may negatively affect male fertility by increasing sperm DNA fragmentation and altering semen quality. Long-term use of citalopram, a similar drug, has shown genotoxic effects on male germ cells in animal studies, suggesting potential risks for abnormal reproductive outcomes in men. ^{1 2 3 5 6}

How does the drug escitalopram differ from other treatments for sperm DNA fragmentation?

Escitalopram is a highly selective serotonin reuptake inhibitor (SSRI) that is more selective and potent than citalopram, potentially offering a different safety and efficacy profile. Unlike citalopram, which has shown genotoxic effects on male germ cells, escitalopram may provide a safer alternative for addressing sperm DNA fragmentation. ^{2 3 5 7 8}

What is the purpose of this trial?

This trial is testing the effects of escitalopram, a common antidepressant, on healthy men with normal fertility and no history of mental health issues. Researchers want to see if this medication affects sperm quality and overall fertility. The results will help doctors advise men who are concerned about fertility and are taking or considering taking escitalopram.

Research Team

Peter Schlegel, MD

Principal Investigator

Weill Medical College of Cornell University

Jonathan Gal, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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 TUNEL value (<7%)

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

Exclusion Criteria

Alcohol consumption greater than 2oz/day

Use of illicit drugs

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Psychotropics and Male Reproduction. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

3. Germany pubmed.ncbi.nlm.nih.gov

Impact of duloxetine on male fertility: A randomised controlled clinical trial. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The effect of SSRIs on Semen quality: A systematic review and meta-analysis. [2022]

5. United States 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. [2023]

6. France pubmed.ncbi.nlm.nih.gov

Semen abnormalities with SSRI antidepressants. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Escitalopram: a second-generation SSRI. [2019]

8. France pubmed.ncbi.nlm.nih.gov

[Escitalopram is more effective than citalopram for the treatment of severe major depressive disorder]. [2022]