Recruiting

Allopregnanolone and Dynamic GABA-A Receptor Plasticity in Selective Serotonin Reuptake Inhibitor Responsive Premenstrual Dysphoric Disorder

ClinicalTrials.gov IDNCT06704594

PhasePHASE4

Enrollment288

SponsorJohns Hopkins University

Age18 Years – 50 Years

SexFEMALE

I'm interested View official listing

Conditions studied

Premenstrual Dysphoric Disorder (PMDD)

About this study

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.

Interventions

Drug: sertraline 50 mg daily — The intervention will be in the form of an oral pill, taken daily, from the day of positive urine ovulation test result until the day of menses onset.
Drug: Placebo Oral Tablet — The placebo oral tablet will be of the same shape, color, and manufacturer as the sertraline 50 mg oral tablets. Tablet will be taken daily, from the day of positive urine ovulation test result until the day of menses onset.

Primary outcomes

Neuroactive Steroid Levels (Post ovulation up to 2 days, up to 5 days pre-menses prediction)

Eligibility information

Inclusion Criteria: * female sex, * fluent in the English language * regular menstrual cycles (24-35 days) * age 18-50 years old * ability to give written informed consent Exclusion Criteria: * psychiatric medication use in the past 2 months * substance use disorder in the past 6 months * lifetime history of psychotic disorder including schizophrenia * schizoaffective disorder, major depression with psychotic features * history of psychiatric disorder other than PMDD in past year * active suicidal ideation with plan or attempt in past 6 months * steroid hormone or hormonal contraceptive use (except levonorgestrel as emergency contraceptive) in past 2 months * pregnancy in past 6 months * history of brain injury * current or history of endocrine disorder including uncontrolled diabetes or thyroid disease * BMI\>40 * History of arrythmias, severe liver impairment, history of seizure disorder * If currently taking the following meds: methylene blue, linezolid * Other prohibited concomitant meds are Monoamine oxidase inhibitors (MAOIs), pimozide, and disulfiram

Study locations

Reproductive Mental Health Center, Baltimore, Maryland 21205 United States
University of Virginia, Charlottesville, Virginia 22903 United States

Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.

Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-10-19.