Pharmacologic agents such as selective serotonin reuptake inhibitors (SSRIs) have been shown to be the most effective treatment for PMDD and are recommended as first-line therapy. Serotonergic modulation was shown to improve both psychological and physical symptoms; a 2013 Cochrane review evaluating SSRIs for PMS concluded that the drug class decreased PMDD symptoms better than placebo. The FDA-approved agents indicated for PMDD include fluoxetine, sertraline, and paroxetine. Citalopram, escitalopram, and fluvoxamine have also been effective at treating PMS/PMDD in various trials. The authors note that when treating PMS/PMDD, SSRIs should be dosed in 1 of 4 strategies: continuous, intermittent, semi-intermittent, and symptom-onset dosing. 

Serotonin norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine, have less data evaluating their efficacy for PMS/PMDD. Anxiolytics (eg, alprazolam) may reduce anxiety, tension, or irritability symptoms when taken during the luteal phase in patients with PMDD. However, due to their sedating effects and abuse potential, benzodiazepines are a second-line therapy and should only be used during the luteal phase to avoid the risk of abuse. Cognitive behavioral therapy (CBT) has shown some benefit in treating patients with severe PMS and PMDD and as an add-on to SSRI therapy.  

Oral contraceptives (OCs), as well as other hormonal treatments, are commonly used to treat PMS/PMDD. Drospirenone/ethinyl estradiol (EE) is considered first-line therapy, followed by levonorgestrel/EE or spironolactone (aldosterone receptor antagonist/K+-sparing diuretic) as second-line therapy, danazol or leuprolide (GnRH agonist) + add back therapy as third-line therapy, and bilateral salpingoophorectomy (BSO) as a last resort for PMDD. 

“Designing an effective treatment plan for women suffering from severe PMS/ PMDD should account for symptoms, lifestyle impact, personal history, prior therapies, and potential side effects,” concluded lead author, Sarah M. Appleton, MD, “It is hypothesized that with further research PMDD actually will be able to be classified into more specific phenotypes allowing clinicians to treat the patient more specifically and successfully.”


Appleton S. Premenstrual Syndrome: Evidence-based Evaluation and Treatment. Clinical Obstetrics and Gynecology. 2018 Jan 2. doi: 10.1097/GRF.0000000000000339. [Epub ahead of print].