Sertraline for Premenstrual Dysphoric Disorder

(BLOOM Trial)

Recruiting at 1 trial location

Overseen By Victoria Paone, B.S.

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Johns Hopkins University

Must not be taking: Psychiatric meds, MAOIs, pimozide, disulfiram

Disqualifiers: Substance use, Psychotic disorder, others

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

Compensation: Varies

Number of Visits: 8

Duration: 2-3 months

288 Participants Needed

Trial Summary

What is the purpose of this trial?

Premenstrual dysphoric disorder (PMDD) is a severe affective disorder impacting millions of women worldwide, thought to be due to altered sensitivity to hormone fluctuations across the menstrual cycle. Neuroactive steroid hormones (NAS) and the gamma-aminobutyric acid (GABA)-A receptor (GABAAR) are thought to play a role in PMDD. This research will assess the blood levels of GABAergic NAS, expression of associated enzymes, and expression of GABAAR subunits across the premenstrual (luteal) phase of the menstrual cycle in healthy controls and individuals with PMDD. Within the PMDD group, the investigators will assess how these measures are affected by a low-dose antidepressant medication versus placebo. The results will provide a comprehensive view of the changes in these systems across the menstrual cycle and will add to the investigator's understanding of the mechanisms that underlie PMDD, as well as therapeutic mechanisms of PMDD treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking psychiatric medications, steroid hormones, hormonal contraceptives, and certain other medications like methylene blue, linezolid, MAOIs, pimozide, and disulfiram at least 2 months before joining the trial.

What data supports the effectiveness of the drug sertraline for treating premenstrual dysphoric disorder (PMDD)?

Research shows that sertraline, a type of antidepressant, helps improve symptoms in women with PMDD. In one study, 68% of women taking sertraline reported feeling much better, compared to 40% who took a placebo (a sugar pill). ^{1 2 3 4 5}

Is sertraline safe for humans?

Sertraline is generally considered safe and well-tolerated in humans, with common side effects including stomach issues and effects on the nervous system. It has a good safety profile even in overdose situations and is used widely for various mood and anxiety disorders. ^{6 7 8 9 10}

How does the drug sertraline differ from other treatments for premenstrual dysphoric disorder?

Sertraline is unique for treating premenstrual dysphoric disorder because it can be taken intermittently, specifically during the luteal phase (the second half of the menstrual cycle), which can be as effective as continuous treatment. This approach may reduce side effects and is different from other treatments that require daily use. ^{2 3 4 11 12}

Research Team

Liisa Hantsoo, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for English-speaking women aged 18-50 with regular menstrual cycles who have Premenstrual Dysphoric Disorder (PMDD). Participants must be able to give written consent. It's not specified who can't join, but typically those with health conditions affecting the study may be excluded.

Inclusion Criteria

I am fluent in English.

My menstrual cycles are regular, lasting 24-35 days.

I can sign and understand the consent form.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants track mood, answer surveys, and complete blood draws across two menstrual cycles. In the second cycle, PMDD participants take sertraline or placebo from ovulation until menses onset.

2-3 months

8 visits (in-person) for PMDD groups, 4 visits (in-person) for control group

Follow-up

Participants are monitored for changes in neuroactive steroid levels and GABAAR subunit expression after treatment

4 weeks

Treatment Details

Interventions

• Sertraline

Trial Overview The trial is testing whether sertraline, an SSRI medication commonly used for depression and PMDD, affects certain brain chemicals during the luteal phase of the menstrual cycle compared to a placebo. The focus is on how this treatment impacts GABA receptors and related neurosteroids in PMDD patients.

Participant Groups

Group I: PMDD with sertraline Active Control 1 Intervention

Participants delegated to the "PMDD with sertraline" arm will be individuals with severe premenstrual symptoms in the luteal phase of the menstrual cycle. Participants will be asked to track mood across two menstrual cycles, answer self-report surveys, and complete eight blood draws (four in each menstrual cycle). In the second cycle, participants in this arm will take a daily pill of 50 mg of sertraline from ovulation until menses onset (end of menstrual cycle 2).

Group II: Control Active Control 1 Intervention

Participants delegated to the "control" arm will be individuals without premenstrual symptoms in the luteal phase of the menstrual cycle. Participants will be asked to track mood across the menstrual cycle, answer self-report surveys, and complete four blood draws.

Group III: PMDD with placebo Placebo Group 1 Intervention

Participants delegated to the "PMDD with placebo" arm will be individuals with severe premenstrual symptoms in the luteal phase of the menstrual cycle. Participants will be asked to track mood across two menstrual cycles, answer self-report surveys, and complete eight blood draws (four in each menstrual cycle). In the second cycle, participants in this arm will take a daily placebo pill from ovulation until menses onset (end of menstrual cycle 2).

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

In a study involving 1251 patients, sertraline was found to have a similar safety profile to other SSRIs, with common side effects like nausea, headache, and diarrhea reported by both groups.

Despite the similarities, sertraline users reported a higher incidence of diarrhea compared to users of other SSRIs, and the study identified over 100 different unlabelled adverse events, indicating the need for ongoing monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in users of sertraline: results from an observational study in psychiatric practice in The Netherlands. Meijer, WE., Heerdink, ER., van Eijk, JT., et al.[2022]

Sertraline is a well-tolerated selective serotonin reuptake inhibitor that effectively treats various depressive and anxiety disorders, showing efficacy even in patients with psychiatric and medical comorbidities.

It is effective for both short-term and long-term management of conditions like major depressive disorder, social anxiety disorder, PTSD, panic disorder, generalized anxiety disorder, and OCD, with a low risk of fatal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evidence-based review of the clinical use of sertraline in mood and anxiety disorders. Sheehan, DV., Kamijima, K.[2022]

References

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

Sertraline in the treatment of premenstrual dysphoric disorder. [2013]

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

Intermittent versus continuous sertraline therapy in the treatment of premenstrual dysphoric disorders. [2022]

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

Efficacy of intermittent, luteal phase sertraline treatment of premenstrual dysphoric disorder. [2019]

4. Croatia pubmed.ncbi.nlm.nih.gov

[Sertraline in the treatment of premenstrual dysphoric disorder]. [2022]

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

Does Symptom-Onset Treatment With Sertraline Improve Functional Impairment for Individuals With Premenstrual Dysphoric Disorder?: A Randomized Controlled Trial. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Adverse events in users of sertraline: results from an observational study in psychiatric practice in The Netherlands. [2022]

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

The selective serotonin reuptake inhibitor sertraline: its profile and use in psychiatric disorders. [2023]

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

Fetal Congenital Cardiac and Vascular Disorders Associated with Sertraline Treatment during Pregnancy: Analysis of FAERS Data. [2022]

9. England pubmed.ncbi.nlm.nih.gov

An evidence-based review of the clinical use of sertraline in mood and anxiety disorders. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Double-blind, multicenter comparative study of sertraline versus amitriptyline in outpatients with major depression. [2013]

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

Luteal phase sertraline treatment for premenstrual dysphoric disorder. Results of a double-blind, placebo-controlled, crossover study. [2022]

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

Treatment of premenstrual dysphoric disorder with sertraline during the luteal phase: a randomized, double-blind, placebo-controlled crossover trial. [2022]