What's Stopping Us? Using GnRH Analogs With Stable Hormone Addback in Treatment-Resistant Premenstrual Dysphoric Disorder: Practical Guidelines and Risk-Benefit Analysis for Long-term Therapy.

Objective: Despite the documented success of gonadotropin-releasing hormone analogs (GnRHa) for the treatment of treatment-resistant premenstrual dysphoric disorder (PMDD), many patients struggle to find providers who have sufficient knowledge of PMDD and its evidence-based treatments and/or who are comfortable treating PMDD after first-line treatment options have failed. Here, we discuss the barriers to initiating GnRHa for treatment-resistant premenstrual dysphoric disorder (PMDD) and offer practical solutions to address these barriers for providers who encounter patients with treatment-resistant PMDD but may not have the necessary expertise or comfort with providing evidence-based treatments (ie, gynecologists, general psychiatrists). We have included supplementary materials including patient and provider handouts, screening tools, and treatment algorithms with the hope that this review may serve as a primer on PMDD and the use of GnRHa with hormonal addback as a treatment, as well as a guideline for clinicians delivering this treatment to patients in need.Options: In addition to offering practical treatment guidelines for first and second lines of treatment for PMDD, this review offers an in-depth discussion of GnRHa for treatment-resistant PMDD.Outcomes: The burden of illness in PMDD is estimated to be similar to that of other mood disorders, and those suffering from PMDD are at a high risk for suicide.Evidence: We present a selective review of relevant clinical trials evidence supporting the use of GnRHa with addback hormones in treatment-resistant PMDD (the most recent evidence cited was published in 2021), highlighting the rationale for addback hormones and presenting the different possible hormonal addback approaches.Values: The PMDD community has and continues to suffer from debilitating symptoms despite the known interventions. This article provides guidance for implementing GnRHa into practice among a broader scope of clinicians including general psychiatrists.Benefits, Harms, and Costs: The primary benefit of implementing this guideline is that a broad range of clinicians beyond reproductive psychiatrists who encounter patients with PMDD will have a template for assessing and treating PMDD and implementing GnRHa treatment when first-line treatments fail. Harms are expected to be minimal; however, some patients may have side effects or adverse reactions to the treatment or may not respond as they had hoped. Costs of GnRHa can be high depending on insurance coverage. We provide information within the guideline to help navigate this barrier.Recommendations: (1) Prospective symptom rating in evaluating for PMDD is necessary for diagnosis and evaluating treatment response. (2) SSRIs and oral contraceptives should be trialed as the first- and second-line treatments for PMDD. (3) When first- and second-line treatments have failed to yield symptom relief, the use of GnRHa with hormone addback should be considered. Risks and benefits of GnRHa should be weighed among clinicians and patients, and potential barriers to access should be discussed.Validation: This article adds to the available systematic reviews on the effectiveness of GnRHa in the treatment of PMDD and Royal College of Obstetrics and Gynecology's guidelines on the treatment of PMDD.

Prevalence of lifetime self-injurious thoughts and behaviors in a global sample of 599 patients reporting prospectively confirmed diagnosis with premenstrual dysphoric disorder.

BACKGROUND: Suicide is the second leading cause of death among Americans ages 10 to 34, with alarming recent increases in suicide rates among those assigned female at birth. A large body of evidence points to menstrual cycle influences on self-injurious thoughts and behaviors (STBs), suggesting that neurobiological hormone sensitivities, such as in premenstrual dysphoric disorder (PMDD), may drive suicide risk in females. However, existing studies of STBs in PMDD use cross-sectional self-report measures of PMDD with poor validity. As a first step to establish accurate prevalence rates of STBs in PMDD, we examined the lifetime prevalence of STBs in a large global survey of patients reporting a diagnosis of PMDD based on daily ratings. METHOD: Individuals with self-reported PMDD symptoms were invited to an online survey through online support groups for PMDD and social media posts from PMDD awareness accounts. Participants reported demographics, whether they had been diagnosed with PMDD by a healthcare provider using daily ratings, STBs using the Columbia Suicide Severity Rating Scale, and history of lifetime comorbid psychiatric diagnoses. RESULTS: Of 2,689 survey completers, 599 (23%) reported a diagnosis with PMDD based on two months of daily ratings and were included in analyses. We observed high rates of lifetime active suicidal ideation (72%), planning (49%), intent (42%), preparing for an attempt (40%), and attempt (34%), as well as non-suicidal self-injury (51%). The majority (70%) of the sample reported at least one lifetime comorbid psychiatric diagnosis. Predictors of lifetime active suicidal ideation included nulliparity, low-to-moderate (vs. high) income, and history of diagnosis with major depression or post-traumatic stress disorder. Predictors of lifetime attempts among those reporting lifetime active ideation included older age, nulliparity, lower income, and history of diagnosis with post-traumatic stress disorder or borderline personality disorder. CONCLUSIONS: These data indicate high rates of STBs among those reporting prospective diagnosis of PMDD and highlight the need for prospective research on mechanisms and prevention of STBs in PMDD. Clinical practice guidelines for PMDD should accommodate comorbidities and recommend frequent screenings for STB risk. STBs should be considered for inclusion in future iterations of the DSM PMDD diagnostic criteria.