Management of Premenstrual Dysphoric Disorder: A Scoping Review.

Premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS) refer to physical, cognitive, or affective symptoms that arise in the late luteal phase and remit with menses. The present work is a clinically focused scoping review of the last twenty years of research on treatment for these disorders. A search of key terms using the PubMed/Medline, the Cochrane Library, Embase, and Web of Science databases was performed, and 194 studies of adult women met initial inclusion criteria for review. Research studies concerning medications, pharmacological and non-pharmacological complementary and alternative medicine treatments, and surgical interventions with the most available evidence were appraised and summarized. The most high-quality evidence can be found for the use of selective serotonin reuptake inhibitors (SSRIs) and combined oral contraceptives (COCs), with gonadotropin releasing hormone (GnRH) agonists and surgical interventions showing efficacy for refractory cases. While there is some evidence of the efficacy of alternative and complementary medicine treatments such as nutraceuticals, acupuncture, and yoga, variability in quality and methods of studies must be taken into account. Reprinted from Int J Womens Health 2022; 14:1783-1801, with permission from Dove Medical Press Ltd. Copyright © 2022.

Current pharmacotherapy approaches and novel GABAergic antidepressant development in postpartum depression.

Postpartum depression has deleterious effects on childbearing persons globally. Existing treatments have been largely extrapolated from those for other forms of depression and have included pharmacotherapy, psychotherapy, and neuromodulation. Hormonal treatments with oestrogen and progestogens, thought to be a rational approach to treatment in response to an emerging literature on the pathophysiology of postpartum depression, have only limited evidence for efficacy to date. Novel antidepressant development with allopregnanolone analogues, in contrast, has proven a promising avenue for the development of rationally designed and efficacious treatments. This state-of-the-art review presents the evidence for the current standard-of-care pharmacotherapy, hormonal treatment, and emerging allopregnanolone analogues for the treatment of postpartum depression along with a discussion of the current understanding of its neuroactive steroid-driven pathophysiology.

Management of Premenstrual Dysphoric Disorder: A Scoping Review.

Premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS) refer to physical, cognitive, or affective symptoms that arise in the late luteal phase and remit with menses. The present work is a clinically focused scoping review of the last twenty years of research on treatment for these disorders. A search of key terms using the PubMed/Medline, the Cochrane Library, Embase, and Web of Science databases was performed, and 194 studies of adult women met initial inclusion criteria for review. Research studies concerning medications, pharmacological and non-pharmacological complementary and alternative medicine treatments, and surgical interventions with the most available evidence were appraised and summarized. The most high-quality evidence can be found for the use of selective serotonin reuptake inhibitors (SSRIs) and combined oral contraceptives (COCs), with gonadotropin releasing hormone (GnRH) agonists and surgical interventions showing efficacy for refractory cases. While there is some evidence of the efficacy of alternative and complementary medicine treatments such as nutraceuticals, acupuncture, and yoga, variability in quality and methods of studies must be taken into account.

Clinical correlates of women endorsing premenstrual suicidal ideation: a cross-sectional study.

BACKGROUND: Prevalence of premenstrual syndrome (PMS) may be as high as 13-18%, but it remains under-recognized and is associated with increased suicidal ideation (SI), plans, and attempts in epidemiological studies. The present study reports on women endorsing premenstrual SI (PMSI) and characterizes this at-risk group and its clinical correlates. METHODS: A cross-sectional study assessed demographics, anxiety and depression severity, psychiatric diagnoses, menstrual symptoms, SI, and trauma in adult women at a major medical center over 11 months. RESULTS: Three hundred two women were assessed. Of 153 participants endorsing premenstrual symptoms, 41 (27%) reported new or worsening concurrent premenstrual passive or active SI. Women who reported PMSI were significantly more likely to be single, unemployed, and childless as well as significantly more likely to report interference from premenstrual symptoms, histories of psychiatric hospitalization, adverse childhood events, suicide attempts, and current and past depression and anxiety compared to women without PMSI. The final regression model indicated the most significant predictors of PMSI were history of a depression diagnosis, severity of current depressive symptoms, and having experienced 3 or more childhood adverse events. CONCLUSION: Nearly one-third of women reporting premenstrual symptoms endorsed concurrent SI, a clinically valuable demonstration of the importance of this predictable cyclic risk factor.

Advances in pharmacotherapy for postpartum depression: a structured review of standard-of-care antidepressants and novel neuroactive steroid antidepressants.

Postpartum depression is one of the most common morbidities of childbearing, yet it is underdiagnosed and undertreated with negative consequences for mother and offspring. Despite the widespread use of standard-of-care antidepressants as the mainstay of treatment for postpartum depression, there is limited evidence on their safety and efficacy due to their slow onset of action and suboptimal outcomes. The emergence of gamma-aminobutyric acidergic neuroactive steroids may offer faster response and remission times and improved patient outcomes. This article reviews the evidence base for the efficacy of standard-of-care antidepressants, hormonal therapeutics including progestins and estradiol, and gamma-aminobutyric acidergic neuroactive steroids in the treatment of postpartum depression, as well as the safety of infant exposure to these agents during lactation.

Antenatal Antidepressant Prescription Associated With Reduced Fetal Femur Length but Not Estimated Fetal Weight: A Retrospective Ultrasonographic Study.

PURPOSE/BACKGROUND: Antidepressants are among the most frequently prescribed medications during pregnancy and may affect fetal weight. Associations between antenatal antidepressant use and ultrasonographic measures of fetal development have rarely been examined. We hypothesized that the prescription of an antenatal antidepressant would be associated with lower estimated fetal weight (EFW). METHODS/PROCEDURES: A retrospective analysis of routine ultrasonographic data extracted from electronic medical records was performed on a cohort of pregnant women with psychiatric diagnoses and grouped according to the presence of an antenatal antidepressant prescription (n = 32 antidepressant-prescribed and n = 44 antidepressant prescription-free). After stratifying for gestational age, comparisons included 13 ultrasonographic parameters, frequency of oligohydramnios and polyhydramnios and growth deceleration, and maternal serum protein markers assessed per routine care, including α-fetoprotein, free ß-human chorionic gonadotropin, and unconjugated estriol levels, using t tests, nonparametric and Fisher tests, and effect sizes (ESs) were computed. FINDINGS/RESULTS: No statistically significant EFW differences between groups at any time point were detected (P > 0.05). Antenatal antidepressant prescription was associated with lower femur length at weeks 33 to 40 (P = 0.046, ES = 0.75) and greater left ventricular diameter at weeks 25 to 32 (P = 0.04, ES = 1.18). No differences for frequency of oligohydramnios or polyhydramnios or growth deceleration were observed (P > 0.05). We did not detect group differences for maternal proteins (P > 0.05). IMPLICATIONS/CONCLUSIONS: Our evidence suggested a lack of association between antenatal antidepressant prescription and lower EFW but indicated an association with lower femur length and greater left ventricular diameter in mid-late gestation. Future research should examine the clinical implications of these findings.

Enhanced primary care and impact on quality of care in Massachusetts.

OBJECTIVES: Using Behavioral Risk Factor Surveillance System (BRFSS) telephone survey data, we evaluated whether individuals who reported access to enhanced primary care features experienced improved quality of care. STUDY DESIGN: Cross-sectional population-level survey. METHODS: We assessed a sample of 16,731 Massachusetts residents contacted by telephone using random-digit dialing, to complete the BRFSS in 2008. A randomized subset of 5693 respondents received an additional 5-question enhanced primary care assessment module. We defined an "enhanced" primary care group as those who reported having a regular, personal provider and responded that their provider "always" or "almost always" 1) had knowledge of their medical history, 2) gave them an appointment right away when necessary, 3) was up-to-date in their knowledge of the patient's specialist care, and 4) asked them about all of their medications. Multivariable logistic regression was used to compare the "enhanced" versus "usual care" groups and assess several quality process measures. RESULTS: Nearly one-third of participants endorsed having indicators of enhanced care, and this group reported significantly higher rates of diabetes process measures (56% vs 38%), cholesterol screening (89% vs 81%), influenza vaccination (57% vs 49%), pneumonia vaccination (51% vs 43%), and lower cost and/or access barriers to care (22% vs 33%). CONCLUSIONS: Enhanced primary care was associated with improved self-reported quality outcomes in a statewide telephone survey. A brief, 5-question module provided a novel population measure of access to enhanced primary care. This is a scalable option for other states hoping to characterize their own primary care improvement efforts through the patient-centered medical home model.

Single dose propranolol does not affect physiologic or emotional reactivity to smoking cues.

BACKGROUND: Smoking cue exposure reactivates salient smoking-related memories, triggering craving to smoke, a phenomenon associated with maintenance of smoking behavior and relapse after periods of abstinence. Acute ß-adrenergic blockade with propranolol reduces physiologic reactivity during subsequent recollection of traumatic events by inhibiting reconsolidation of reactivated memories in a process called memory reconsolidation blockade. OBJECTIVE: The objective of this study is to determine whether a single dose of propranolol prior to retrieval of smoking-related memories reduces subsequent physiologic reactivity to personally salient smoking imagery scripts in current smokers. METHODS: Fifty-four overnight-abstinent, adult smokers received a single-dose propranolol or placebo prior to reactivation of smoking-related memories in a randomized, double-blind, placebo-controlled trial and resumed smoking afterward. One week later, skin conductance (SC), heart rate (HR), left corrugator electromyogram (EMG), self-reported emotional state, and craving were assessed following script-driven imagery with neutral and personalized smoking-related scripts. RESULTS: Smoking scripts were associated with increased physiologic activation (SC, HR, EMG), craving, and negative emotional state compared with neutral scripts. Propranolol did not moderate the effect of script type on any outcome. CONCLUSION: Personalized smoking script-driven imagery robustly increased physiologic activation, negative emotional state, and craving, and a single dose of propranolol prior to memory reactivation did not moderate this effect.

Accuracy of race, ethnicity, and language preference in an electronic health record.

BACKGROUND: Collection of data on race, ethnicity, and language preference is required as part of the "meaningful use" of electronic health records (EHRs). These data serve as a foundation for interventions to reduce health disparities. OBJECTIVE: Our aim was to compare the accuracy of EHR-recorded data on race, ethnicity, and language preference to that reported directly by patients. DESIGN/SUBJECTS/MAIN MEASURES: Data collected as part of a tobacco cessation intervention for minority and low-income smokers across a network of 13 primary care clinics (n = 569). KEY RESULTS: Patients were more likely to self-report Hispanic ethnicity (19.6 % vs. 16.6 %, p < 0.001) and African American race (27.0 % vs. 20.4 %, p < 0.001) than was reported in the EHR. Conversely, patients were less likely to complete the survey in Spanish than the language preference noted in the EHR suggested (5.1 % vs. 6.3 %, p < 0.001). Thirty percent of whites self-reported identification with at least one other racial or ethnic group, as did 37.0 % of Hispanics, and 41.0 % of African Americans. Over one-third of EHR-documented Spanish speakers elected to take the survey in English. One-fifth of individuals who took the survey in Spanish were recorded in the EHR as English-speaking. CONCLUSION: We demonstrate important inaccuracies and the need for better processes to document race/ ethnicity and language preference in EHRs.

Varenicline for Smoking Cessation in Schizophrenia: Safety and Effectiveness in a 12-Week, Open-Label Trial.

OBJECTIVES: Varenicline was approved by the FDA in 2006. In 2009, based largely on case reports, the FDA issued a warning of possible adverse neuropsychiatric effects including depression and suicidal thoughts and behavior for varenicline and bupropion. Prospective trials of varenicline have not reported increased incidence of psychiatric adverse events other than sleep disturbance, but smokers with major mental illness have been excluded from large prospective trials of varenicline to date. We sought to evaluate the effect of a standard open-label 12-week varenicline trial on prospectively assessed safety and smoking outcomes in stable, treated adults with schizophrenia spectrum disorder and nicotine dependence. METHODS: One-hundred-and-twelve stable outpatients who smoked >10 cigarettes/day participated in a 12-week, open-label, smoking cessation trial of varenicline and weekly group cognitive behavioral therapy. Participants took varenicline for 4 weeks before attempting cessation. Trained raters collected safety and smoking outcome data weekly. RESULTS: Participants demonstrated improved psychotic symptoms, depressive symptoms and nicotine withdrawal symptoms from baseline to week 12 or early termination. At the end of 12 weeks open label treatment, the 14- and 28-day continuous abstinence rates were 47.3 and 34%, respectively. Expired CO declined significantly during treatment in those who did not achieve abstinence. CONCLUSIONS: This prospective study suggests that varenicline may be well-tolerated and effective for smoking cessation in combination with group CBT in stable outpatients with schizophrenia, a group with high rates of smoking and smoking-attributable morbidity and mortality.

Varenicline as a smoking cessation aid in schizophrenia: effects on smoking behavior and reward sensitivity.

RATIONALE: Smoking rates are up to five times higher in people with schizophrenia than in the general population, placing these individuals at high risk for smoking-related health problems. Varenicline, an α4ß2 nicotinic acetylcholine receptor partial agonist, is a promising aid for smoking cessation in this population. To maximize treatment efficacy while minimizing risks, it is critical to identify reliable predictors of positive response to varenicline in smokers with schizophrenia. OBJECTIVES: Negative symptoms of schizophrenia are related to dysfunctions in the brain reward system, are associated with nicotine dependence, and may be improved by nicotine or nicotinic receptor agonists, suggesting that smoking cessation may be especially difficult for patients with substantial negative symptoms. The purpose of the study was to evaluate negative symptoms as predictors of response to varenicline. METHODS: Patients with schizophrenia (N = 53) completed a 12-week smoking cessation trial combining varenicline with cognitive behavioral therapy. Negative symptoms were assessed via the Scale for the Assessment of Negative Symptoms (Andreasen 1983). Outcomes included smoking abstinence as assessed by self-report and expired carbon monoxide. Change in performance on a probabilistic reward task was used as an index of change in reward sensitivity during treatment. RESULTS: At week 12, 32 participants met criteria for 14-day point-prevalence abstinence. Patients with lower baseline symptoms of affective flattening (more typical affect) were more likely to achieve smoking abstinence and demonstrated larger increases in reward sensitivity during treatment. CONCLUSIONS: These data suggest that affective flattening symptoms in smokers with schizophrenia may predict response to varenicline.

A double-blind, placebo-controlled trial of the NMDA glycine site antagonist, GW468816, for prevention of relapse to smoking in females.

Relapse to smoking is common after initial abstinence with pharmacotherapy and behavioral support and represents a major clinical challenge. Although mechanisms underlying relapse to smoking have not been elucidated, preclinical studies suggest that glutamate receptors may be involved. We sought to test a selective antagonist of the glycine coagonist site on the glutamate N-methyl-D-aspartate receptor, GW468816, for prevention of relapse in recently abstinent smokers. To do so, we enrolled 264 healthy female smokers in an open 8-week smoking cessation intervention with behavioral therapy and a standard dose of transdermal nicotine replacement therapy with taper and additional gum or lozenge as needed for nicotine withdrawal symptoms. Ninety-eight participants achieved 7-day point prevalence abstinence and were randomized into a 5-week double-blind, placebo-controlled, relapse-prevention trial of GW468816 (200 mg/d) and then followed for 60 days after randomization. There was no effect of treatment on abstinence rates at the end of treatment (χ² [1, n = 96] = 0.168, P = 0.838), on the rates of relapse (χ² [1, n = 98] = 0.031, P = 1.000) or lapse (χ² [1, n = 62] = 0.802, P = 0.423), or on time to relapse (χ² [1, n = 98) = 0.001, P = 0.972). No significant relationships were detected between plasma GW468816 concentrations and abstinence, time to relapse, or self-reported craving. In conclusion, despite promising preclinical data that support the use of a selective NMDA glycine site antagonist for prevention of relapse to smoking, we observed no effect of GW468816 on relapse or lapse rates, time to relapse, or craving compared to placebo.