Selective Serotonin Reuptake Inhibitors (SSRIs)

Seek medical advice before using Selective Serotonin Reuptake Inhibitors (SSRIs), as they cannot be purchased over the counter.

What Are Selective Serotonin Reuptake Inhibitors (SSRIs)?

Selective serotonin reuptake inhibitors (SSRIs) are anti-depressants that have been successful in reducing mood symptoms. This includes:

• Fluoxetine (Prozac)

• Paroxetine (Paxil, Pexeva)

• Sertraline (Zoloft)¹

How Do SSRIs Work?

These medications increase the concentration of a neurotransmitter (chemical messenger) in the brain called serotonin, which is thought to have a good influence on mood, emotion and sleep. After carrying a message, serotonin is usually reabsorbed by the nerve cells (known as "reuptake"). SSRIs work by blocking ("inhibiting") reuptake, meaning more serotonin is available to pass further messages between nearby nerve cells.

But you have to take SSRIs for at least three months before they start working. They weren't found to be more effective when taken continuously rather than only during the second half of the cycle.

It's important for women who are considering taking antidepressants to know what side effects they could have. SSRIs can cause things like nausea, sleep problems, and decreased libido.²

What Is the Efficacy of SSRIs for PMS?

Methods: Studies were done which included large-scale systematic reviews and meta-analyses of 29–34 randomized controlled trials, assessing the efficacy of SSRIs in treating PMS/PMDD. They compared continuous vs luteal-phase dosing and measured symptom reduction, response rates, and side effects. Participant data ranged from hundreds to over 4,000 women across varied age groups and symptom severity.

Results: SSRIs significantly reduced PMS/PMDD symptoms compared to placebo, with moderate-to-large effect sizes. Continuous dosing was slightly more effective than luteal-phase dosing, though both were beneficial. Side effects like nausea and fatigue were more common with SSRIs, leading to higher dropout rates than placebo. No single SSRI proved superior across studies.

Conclusion: SSRIs are effective and recommended as a first-line treatment for moderate-to-severe PMS and PMDD. Side effects are common but generally manageable. Treatment choice should be individualized based on symptom severity, tolerance, and patient preference.^3,4,5,6

What Are the Side Effects of SSRIs?

Short-term effects: Nausea, decreased energy, drowsiness, fatigue, and sweating.

Long-term effects: Sexual disturbances, sleep disturbance, and weight gain.⁷

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Medically reviewed by

Dr. Yash Bahuguna

Researched by

Dr. Inara Isani

Written by

Avantika Sukhia

References

1. Chu A, Wadhwa R. Selective serotonin reuptake inhibitors. InStatPearls [internet] 2023 May 1. StatPearls Publishing.

2. Institute for Quality and Efficiency in Health Care (IQWiG). Premenstrual syndrome: Learn more – Treatment for PMS [Internet]. Cologne (DE): IQWiG; 2022 May 18 [cited 2025 Apr 23]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279264/

3. Jespersen C, Lauritsen MP, Frokjaer VG, Schroll JB. Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder. Cochrane Database of Systematic Reviews. 2024(8).

4. Reilly TJ, Wallman P, Clark I, Knox CL, Craig MC, Taylor D. Intermittent selective serotonin reuptake inhibitors for premenstrual syndromes: A systematic review and meta-analysis of randomised trials. Journal of Psychopharmacology. 2023 Mar;37(3):261-7.

5. Shah NR, Jones JB, Aperi J, Shemtov R, Karne A, Borenstein J. Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder: a meta-analysis. Obstetrics & Gynecology. 2008 May 1;111(5):1175-82.

6. Dimmock PW, Wyatt KM, Jones PW, O'Brien PS. Efficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: a systematic review. The lancet. 2000 Sep 30;356(9236):1131-6.

1. Ferguson JM. SSRI antidepressant medications: adverse effects and tolerability. Primary care companion to the Journal of clinical psychiatry. 2001 Feb;3(1):22.