The magnitude and sustainability of treatment benefit of zuranolone on function and well-being as assessed by the SF-36 in adult patients with MDD and PPD: An integrated analysis of 4 randomized clinical trials.

BACKGROUND: Major depressive disorder (MDD) and postpartum depression (PPD) are disabling conditions. This integrated analysis of MDD and PPD clinical trials investigated the impact of zuranolone-a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and neuroactive steroid under investigation for adults with MDD and approved as an oral, once-daily, 14-day treatment course for adults with PPD in the US-on health-related quality of life, including functioning and well-being, as assessed using the 36-item Short Form Health Survey V2 (SF-36). METHODS: Integrated data from 3 MDD (201B, MOUNTAIN, WATERFALL) and 1 PPD trial (ROBIN) for individual SF-36 domains were compared for zuranolone (30- and 50-mg) vs placebo at Day (D)15 and D42. Comparisons between zuranolone responders (≥50 % reduction from baseline in 17-item Hamilton Depression Rating Scale total score) and nonresponders were assessed. RESULTS: Overall, 1003 patients were included (zuranolone, n = 504; placebo, n = 499). Significant differences in change from baseline (CFB) to D15 for patients in zuranolone vs placebo groups were observed in 6/8 domains; changes were sustained or improved at D42, with significant CFB differences for all 8 domains. Zuranolone responders had significantly higher CFB scores vs nonresponders for all domains at D15 and D42 (p < 0.001). LIMITATIONS: Two zuranolone doses were integrated across populations of 2 disease states with potential differences in functioning, comorbidities, and patient demographics. All p-values presented are nominal. CONCLUSIONS: Integrated data across 4 zuranolone clinical trials showed improvements in functioning and well-being across all SF-36 domains. Benefits persisted after completion of treatment course at D42.

Zuranolone for the Treatment of Adults With Major Depressive Disorder: A Randomized, Placebo-Controlled Phase 3 Trial.

OBJECTIVE: This study assessed the efficacy and safety of a 14-day treatment course of once-daily zuranolone 50 mg, an investigational oral positive allosteric modulator of the γ-aminobutyric acid type A (GABAA) receptor, for the treatment of major depressive disorder. METHODS: Patients 18-64 years of age with severe major depressive disorder were enrolled in this randomized, double-blind, placebo-controlled trial. Patients self-administered zuranolone 50 mg or placebo once daily for 14 days. The primary endpoint was change from baseline in total score on the 17-item Hamilton Depression Rating Scale (HAM-D) at day 15. Safety and tolerability were assessed by incidence of adverse events. RESULTS: Of 543 randomized patients, 534 (266 in the zuranolone group, 268 in the placebo group) constituted the full analysis set. Compared with patients in the placebo group, patients in the zuranolone group demonstrated a statistically significant improvement in depressive symptoms at day 15 (least squares mean change from baseline HAM-D score, -14.1 vs. -12.3). Numerically greater improvements in depressive symptoms for zuranolone versus placebo were observed by day 3 (least squares mean change from baseline HAM-D score, -9.8 vs. -6.8), which were sustained at all visits throughout the treatment and follow-up periods of the study (through day 42, with the difference remaining nominally significant through day 12). Two patients in each group experienced a serious adverse event; nine patients in the zuranolone group and four in the placebo group discontinued treatment due to adverse events. CONCLUSIONS: Zuranolone at 50 mg/day elicited a significantly greater improvement in depressive symptoms at day 15, with a rapid time to effect (day 3). Zuranolone was generally well tolerated, with no new safety findings compared with previously studied lower dosages. These findings support the potential of zuranolone in treating adults with major depressive disorder.

Patient-Specific Considerations, the GABA Pathway, and New Clinical Trial Data on Neuroactive Steroids in MDD and PPD.

Major depressive disorder (MDD) and major depressive episode with peripartum onset, commonly referred to as postpartum depression (PPD), are among the most common psychiatric illnesses and are leading contributors to disability and suicide. Standard of care antidepressants are the cornerstone of MDD treatment; however, nonadherence to antidepressants has been widely recognized as one of the reasons for treatment failure in MDD. Delayed response in current therapies can take up to 4 or even 8 weeks for patients to experience therapeutic benefits. Low treatment response rates are seen in a considerable amount of patients, with early-stage treatment-resistant depression (TRD) affecting 50% of patients receiving first-line treatments and 30% developing into substantive TRD. Given these treatment gaps, there is an urgent need to develop novel antidepressants with a faster onset of action and shorter treatment course, which could improve adherence and treatment response rates. The neurobiology of depression is multifactorial, with different pathways converging on the development of the neurocircuit dysfunction characteristic of depression. Neuroactive steroids play an important role in modulating acute and chronic stress via their phasic and tonic inhibitory effects on select GABAA receptors, ultimately modulating neurocircuit function. With clinical recognition of the importance of neurosteroids in the modulation of GABAA signaling pathways, researchers have developed novel neuroactive steroid-based pharmacotherapies that have been tested in clinical studies. Given their rapid onset of action and shorter treatment course, these novel antidepressants have the potential to change the treatment paradigm for MDD and PPD.

Zuranolone in Major Depressive Disorder: Results From MOUNTAIN-A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial.

Objective: To evaluate the efficacy and safety of zuranolone, an investigational neuroactive steroid and GABAA receptor positive allosteric modulator, in major depressive disorder (MDD).Methods: The phase 3, double-blind, randomized, placebo-controlled MOUNTAIN study enrolled adult outpatients with DSM-5-diagnosed MDD, 17-item Hamilton Depression Rating Scale total score (HDRS-17) ≥ 22, and Montgomery-Asberg Depression Rating Scale total score ≥ 32. Patients were randomized to treatment with zuranolone 20 mg, zuranolone 30 mg, or placebo for 14 days, followed by an observation period (days 15-42) and an extended follow-up (days 43-182). The primary endpoint was change from baseline (CFB) in HDRS-17 at day 15.Results: 581 patients were randomized to receive zuranolone (20 mg, n = 194; 30 mg, n = 194) or placebo (n = 193). Day 15 HDRS-17 least-squares mean (LSM) CFB was -12.5 (zuranolone 30 mg) vs -11.1 (placebo; P = .116). Improvement vs placebo was significant at days 3, 8, and 12 (all P < .05). LSM CFB (zuranolone 20 mg vs placebo) was not significant at any measured time point. Post hoc analyses of zuranolone 30 mg in patients with measurable plasma zuranolone concentration and/or severe disease (baseline HDRS-17 ≥ 24) showed significant improvement vs placebo at days 3, 8, 12, and 15 (all P < .05). Incidence of treatment-emergent adverse events was similar between zuranolone and placebo groups; the most common (≥ 5%) were fatigue, somnolence, headache, dizziness, diarrhea, sedation, and nausea.Conclusions: MOUNTAIN did not meet its primary endpoint. Significant rapid improvements in depressive symptoms were observed with zuranolone 30 mg at days 3, 8, and 12. Zuranolone was generally well tolerated in patients with MDD.Trial Registration: ClinicalTrials.gov identifier: NCT03672175.

Outpatient Pharmacogenomic Screenings to Prevent Addiction, Overdose, and Suicide.

Point-of-care genetic testing for single nucleotide polymorphisms (SNPs) to improve psychiatric treatment in outpatient settings remains a challenge. The presence or absence of certain genomic alleles determines the activity of the encoded enzymes, which ultimately defines the individual's drug metabolism rate. Classification of poor metabolizers (PMs) and rapid/ultrarapid metabolizers (RMs/UMs) would facilitate personalization and precision of treatment. However, current pharmacogenomic (PGx) testing of multiple genes is comprehensive and requires quantitative analyses for interpretations. We recommend qualitative, fast-track, point-of-care screenings, which are one- or-two gene-based analyses, as a quick initial screening tool to potentially eliminate the need for an expensive quantitative send-out test, which is a costly and lengthy process. We speculate that these tests will be relevant in two major scenarios: 1) clinical psychiatry for treating disease states such as major depressive disorder (MDD) and posttraumatic stress disorder (PTSD), where trial and error is still the mainstay of drug selection and symptom management, a process that is associated with significant delay in optimizing individualized treatment and dose, and thus response; and 2) pain management, where quickly determining an effective level of analgesia while avoiding a toxic level can cause a drastic improvement in mental health.

Effects of Flibanserin on Subdomain Scores of the Female Sexual Function Index in Women With Hypoactive Sexual Desire Disorder.

INTRODUCTION: Flibanserin treatment increases sexual desire and satisfying sexual events while decreasing distress in certain women diagnosed with acquired, generalized hypoactive sexual desire disorder (HSDD). Additional aspects of sexual function and the time course of response have not been fully characterized. AIM: To evaluate changes in sexual function assessed by the subdomains of the Female Sexual Function Index (FSFI) in women with HSDD treated with flibanserin. METHODS: FSFI data pooled from 3 pivotal flibanserin trials in premenopausal women (flibanserin = 1,165; placebo = 1,203) and FSFI data from one complete flibanserin trial in postmenopausal women (flibanserin = 432; placebo = 463) were subjected to post-hoc analyses. For each FSFI subdomain, least squares mean change from baseline was calculated at each assessment visit (treatment weeks 4, 8, 16, 24) and treatment groups were compared using analysis of covariance. Standardized effect size (Cohen's d) was also determined for each FSFI subdomain. MAIN OUTCOME MEASURE: Changes from baseline in FSFI subdomains. RESULTS: Compared to placebo, both premenopausal (P < .02) and postmenopausal (P < .045) patients in the flibanserin group reported significantly greater increases over baseline in the FSFI subdomain scores of desire, arousal, lubrication, orgasm, and satisfaction. In premenopausal patients, significant improvements were observed at the first assessment of response (week 4) and were maintained through week 24. In postmenopausal patients, significant improvements were observed at week 4 for desire and arousal, while significant improvements in lubrication, orgasm, and satisfaction were observed at week 8. At week 24, excluding the pain subdomain, standardized effect sizes ranged from 0.18 to 0.28 in the premenopausal cohort and 0.12 to 0.29 in the postmenopausal cohort. In both pre- and postmenopausal patients, improvements in pain were smaller and largely undifferentiated between treatment groups. CLINICAL IMPLICATIONS: While variations in time to response should be taken into consideration, on average, the beneficial impact of flibanserin on overall sexual function occurs within the first month of treatment. The data also suggest that the response to flibanserin is sustained for the duration of treatment. STRENGTHS AND LIMITATIONS: Sexual function assessments were performed in a large cohort of 2,368 premenopausal women and 895 postmenopausal women. However, the FSFI assesses changes over a 1-month period and time points earlier than 4 weeks could not be assessed. CONCLUSION: These analyses suggest that assessment of benefit of flibanserin in HSDD should include improvements across all domains of sexual function, not only desire. Simon JA, Clayton AH, Goldstein I, et al. Effects of Flibanserin on Subdomain Scores of the Female Sexual Function Index in Women With Hypoactive Sexual Desire Disorder. Sex Med 2022;10:100570.

Sexual dysfunction with major depressive disorder and antidepressant treatments: impact, assessment, and management.

INTRODUCTION: Sexual dysfunction (SD) is a symptom of depression in ≈70% of patients presenting with major depressive disorder (MDD). Antidepressant medications (AD) and adjunctive treatments may further contribute to SD and complicate evaluation and management. AREAS COVERED: A systematic literature search of PubMed, Ovid MEDLINE and Cochrane databases for MDD, SD, classes of antidepressants, etc. was performed with a focus on 2014 to June 2021. SSRIs are associated with 70% treatment-emergent sexual dysfunction (TESD), SNRIs and tricyclics have rates of TESD of 40-45%, and antidepressant medications without SRI effects or with additional unique mechanisms of action have rates similar to placebo (<10%). Appropriate assessment at baseline and throughout treatment, consideration of patient preferences in prescribing, addressing modifiable factors (comorbid medical/psychiatric conditions, substances, relationship difficulties), and utilizing management strategies of switching to an AD with less SD, adding an antidote/adjunctive therapy or lowering the dose are discussed. EXPERT OPINION: MDD and antidepressant treatment contribute to SD in a high percentage of patients. Treating to remission reduces SD as a symptom of depression. Frequent assessment and targeted management strategies may be effective in preventing or addressing SD. Secondary outcomes like impact on adherence, relationships and self-image should also be considered.

Prespecified and Integrated Subgroup Analyses from the RECONNECT Phase 3 Studies of Bremelanotide.

Background: Hypoactive sexual desire disorder (HSDD), the most prevalent female sexual dysfunction, is characterized as persistent diminished desire for sexual activity accompanied by distress. The efficacy and safety of bremelanotide, a melanocortin receptor agonist approved by the U.S. Food and Drug Administration for treatment of acquired generalized HSDD in premenopausal women, were established in the phase 3 RECONNECT studies, two identically designed double-blind randomized placebo-controlled studies with an optional 52-week open-label extension. This report investigates efficacy of bremelanotide versus placebo according to prespecified subgroups (age, weight, body mass index [BMI], and bioavailable testosterone) in the RECONNECT studies. Materials and Methods: Patients self-administered bremelanotide 1.75 mg or placebo subcutaneously using an autoinjector, as needed, before sexual activity for 24 weeks. Efficacy was assessed using change from baseline to end-of-study for Female Sexual Function Index desire domain and Female Sexual Distress Scale-Desire/Arousal/Orgasm Item 13 for bremelanotide versus placebo. Results: Among 1202 patients included in the integrated and subgroup analyses, bremelanotide achieved statistically significant improvements in measures of increased desire and decreased distress associated with low desire across all age, weight, and BMI subgroups, and all baseline bioavailable testosterone quartiles, with few exceptions. Bremelanotide was further associated with statistically significant increases in reported sexual desire (p < 0.05) in patients not taking hormonal contraceptives, and with a numerical advantage in those taking hormonal contraceptives. Patients treated with bremelanotide experienced decreased distress compared with those in the placebo group at levels of statistical significance (p < 0.05) regardless of hormonal contraceptive use. Statistically significant improvements were observed in the presence or absence of decreased arousal, and regardless of HSDD duration. Conclusions: Bremelanotide was associated with statistically significant improvements in sexual desire and reduced distress across several prespecified subgroups, with few exceptions.

Safety Profile of Bremelanotide Across the Clinical Development Program.

Background: Bremelanotide, a melanocortin receptor agonist, is Food and Drug Administration (FDA)-approved for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder. Methods: Review of bremelanotide's safety profile from the clinical development program (phases 1 through 3). Results: The clinical development program comprised 3500 subjects in 43 completed studies. In the phase 3 studies, subjects took bremelanotide for up to 18 months. The most common adverse events (AEs) were nausea (40.0% vs. 1.3%), flushing (20.3% vs. 1.3%), headache (11.3% vs. 1.9%), and injection site reactions (5.4 vs. 0.5), bremelanotide versus placebo groups, respectively, in the integrated double-blind portion of the phase 3 studies (N = 1247). Nausea was the most common reason for bremelanotide discontinuation. There were no deaths; a few subjects experienced serious AEs. Focal hyperpigmentation was rare when bremelanotide was dosed in accordance with label recommendations, but it occurred in more than one-third of subjects following up to 16 consecutive daily dosings. Small and transient but statistically significant blood pressure increases were observed during ambulatory blood pressure monitoring. Most drug-drug interactions were not clinically significant, except for interactions that lowered plasma concentrations of indomethacin and naltrexone. In the double-blind portion of the integrated phase 3 studies, 70% of the bremelanotide group proceeded to the open-label phase of the studies versus 87% of those on placebo. Conclusions: The AEs associated with bremelanotide are mostly mild to moderate. Although not deemed clinically important, bremelanotide should be used with caution in patients at risk of cardiovascular disease, and blood pressure should be well controlled during treatment. Clinical Trial Registration number: NCT02333071 [Study 301] and NCT02338960 [Study 302].

Pharmacotherapy for Sexual Dysfunction in Women.

PURPOSE OF REVIEW: This review article discusses the controversy in the DSM-5 conceptualization and diagnostic criteria for female sexual dysfunction (FSD). An overview of recent studies on available treatments for hypoactive sexual desire disorder (HSDD), female sexual arousal disorder (FSAD), and genitopelvic pain/penetration disorder (GPPD) is provided. RECENT FINDINGS: Include delineation of the process of care for pre- and postmenopausal women with HSDD; release of global position statement on testosterone therapy in women; updates on efficacy and safety of vaginal estrogen for genitourinary syndrome of menopause and bremelanotide for HSDD; removal of flibanserin alcohol REMS; and development of new technology to enhance bioavailability and brain delivery of treatments. The DSM-5 revision combining HSDD and FSAD into one diagnostic category is a less accurate characterization of these separate disorders and may hinder access to demonstrated effective treatments for the women with these conditions. There are a wide range of pharmacological, other physiological, and psychological treatment options available for women with FSD, which can be offered based on their specific symptoms, potential benefits/risks, and preferences.

Including partners in discussions of sexual side effects from breast cancer: a qualitative study of survivors, partners, and providers.

PURPOSE: Ensuring there are clear standards for addressing cancer-related sexual side effects is important. Currently, there are differences in two leading sets of clinical guidelines regarding the inclusion of survivors' romantic partners into clinical discussions between survivors and their providers about this issue. To help refine guidelines, we examine breast cancer survivor, partner, and oncology provider perspectives about including partners in discussions about cancer-related sexual side effects in a secondary analysis of a broader qualitative study. METHODS: Partnered female breast cancer survivors (N = 29) completed online surveys, and intimate partners of breast cancer survivors (N = 12) and breast oncology providers (N = 8) completed semi-structured interviews. Themes were derived from thematic content analysis. RESULTS: Among survivors who reported a discussion with their provider, fewer than half indicated their partner had been present, despite most survivors expressing it was - or would have been - helpful to include their partner. Partners also largely indicated being included was or would have been helpful, when welcomed by the survivor. Providers similarly emphasized the importance of survivors' autonomy in deciding whether to discuss sexual concerns in the presence of a partner. CONCLUSIONS: Partners were infrequently included in conversations about cancer-related sexual side effects, even though survivors, partners, and providers alike expressed value in these discussions occurring with the couple together - when that is the survivor's preference. Findings suggest future clinical guidelines should emphasize that incorporating partners into clinical discussions about sexual concerns is important for many breast cancer patients. Soliciting and enacting patients' preferences is essential for truly patient-centered care.

Clinically Meaningful Benefit in Women with Hypoactive Sexual Desire Disorder Treated with Flibanserin.

BACKGROUND: The efficacy of flibanserin in treating hypoactive sexual desire disorder (HSDD) is based upon statistically significant improvements in sexual desire, satisfying sexual events, and distress. However, clinically meaningful benefit has not been well characterized. AIM: Evaluate clinically meaningful benefit of flibanserin. METHODS: Data were pooled from 3 pivotal trials evaluating flibanserin 100 mg qhs in premenopausal women (flibanserin, n = 1192; placebo, n = 1215). Flibanserin trial data in postmenopausal women (flibanserin, n = 450; placebo, n = 476) were analyzed separately. Clinically meaningful benefit was evaluated by the Patient Global Impression of Improvement (PGI-I). Responders were determined through anchor-based analyses that used the PGI-I for key efficacy endpoints: satisfying sexual events (SSE), desire domain of the Female Sexual Function Index (FSFI-d), and distress associated with decreased sexual desire (FSDS-R13). Odds ratios were calculated to assess effect size and Kaplan-Meier analyses were performed to estimate onset time for treatment benefit. OUTCOMES: PGI-I, anchor-based analyses for key efficacy endpoints (SSE, FSFI-d, FSDS-R13), odds ratios, onset time for treatment benefit. RESULTS: Based on the PGI-I, more patients reported clinically meaningful benefit with flibanserin treatment versus placebo (49.8% vs 33.6%, premenopausal cohort; 40.5% vs 28.7%, postmenopausal cohort). In anchor-based analyses, responder rates were significantly higher for premenopausal women on flibanserin (46.1%-55.2%) than placebo (34.1%-44.2%) for all 3 key efficacy endpoints (P < .0001). Responder rates for postmenopausal women on flibanserin were higher compared to placebo for SSE (29.8% vs 22.9%; P = .015) and FSFI-d (38.9% vs 26.3%; P = .0001). Odds ratios for key endpoints indicated that premenopausal women were 2.0-2.4 times as likely to be responders with flibanserin treatment compared to placebo. Postmenopausal women were 1.6 times as likely to be responders with flibanserin for FSFI-d. Kaplan-Meier analyses indicated significant separation between flibanserin and placebo for the key endpoints in both premenopausal and postmenopausal cohorts (log-rank tests P < .01) with earlier median response times among patients receiving flibanserin. CLINICAL IMPLICATIONS: Patient-reported benefit assessments such as the PGI-I capture the patient's perspective and may be a useful approach in assessing overall clinical meaningfulness for sexual dysfunction therapies. STRENGTHS AND LIMITATIONS: Strengths include a well-powered study with large enrollment, use of validated instruments, and self-assessment of treatment benefit. Limitations include pooling of trial data in premenopausal women with slightly different study designs and use of an endpoint (SSE) indirectly related to HSDD. CONCLUSION: Assessment of clinically meaningful benefit and additional responder analyses provide further support for flibanserin's efficacy beyond numerical improvements in endpoint measures. Simon JA, Clayton AH, Kim NN, et al. Clinically Meaningful Benefit in Women with Hypoactive Sexual Desire Disorder Treated with Flibanserin. Sex Med 2022;10:100476.

The neurobiology of bremelanotide for the treatment of hypoactive sexual desire disorder in premenopausal women.

Hypoactive sexual desire disorder (HSDD) is a common female sexual dysfunction and is estimated to affect approximately 10% of women in the United States. It has been suggested that HSDD is associated with an imbalance of hormone and neurotransmitter levels in the brain, resulting in decreased excitation, increased inhibition, or a combination of both. Evidence suggests neurotransmitters, including dopamine (DA), norepinephrine, and serotonin, as well as hormones such as estradiol and testosterone, contribute to female sexual desire and response. Current treatments for HSDD include psychotherapy, and two US Food and Drug Administration-approved medications for premenopausal women: flibanserin, a serotonin mixed agonist and antagonist, and bremelanotide, a melanocortin receptor (MCR) agonist. Melanocortins are endogenous neuropeptides associated with the excitatory pathway of the female sexual response system. MCRs are found throughout the body, including the brain. Bremelanotide is an MCR agonist that nonselectively activates several of the receptor subtypes, of which subtype 4 (MC4R) is the most relevant at therapeutic doses. MC4R is predominantly expressed in the medial preoptic area (mPOA) of the hypothalamus in the brain, and is important for female sexual function. Animal studies suggest that bremelanotide may affect female sexual desire by activating presynaptic MC4Rs on neurons in the mPOA of the hypothalamus, leading to increased release of DA, an excitatory neurotransmitter that increases sexual desire. This review presents what is known about the mechanism of action of bremelanotide in the context of treating HSDD.

An Innovative Model of Behavior Management to Address Behavioral Emergencies in the Acute Medical Inpatient Setting: Pilot Data.

Workplace violence in healthcare is a significant and costly problem. The majority of violent events that occur in the medical inpatient setting are perpetrated by patients against staff and occur during a behavioral emergency. The primary purpose of this study was to evaluate the impact of an innovative model of behavior management on occurrence of behavioral emergencies and staff comfort and competence in managing difficult patient behaviors. This model consists of primary, secondary, and tertiary interventions provided by a clinical psychologist which include proactive training for hospital staff and consultation-liaison services for behavior management. Forty-six staff at the University of Virginia Medical Center completed a 1-h training on preventing and managing difficult patient behavior. Self-report data on comfort and competence in managing challenging patient behaviors was collected at baseline, immediately following the intervention, and one and three months post-intervention. Behavioral emergencies were tracked for the intervention unit and a comparison unit. The occurrence of behavioral emergencies decreased by 50% in the three months following the intervention compared to a 142% increase on the comparison unit. Staff reported the greatest increase in confidence from baseline to three months post-intervention on caring for patients with psychiatric illnesses, managing verbal abuse, being supported by medical center leadership, having clear roles and responsibilities, and effectiveness of the skills and strategies used to manage difficult patient behavior. The results of this study provide preliminary support for the use of a comprehensive model for managing the behavioral needs of medical inpatients.

Major Depressive Disorder, Suicides, and the Role of Dimensional Psychiatry for Triaging in Primary Care Settings: A Case Series Retroanalysis.

Objective: The goal was to promote early diagnosis and referral of patients with depressive symptomology in the primary care setting using a biopsychosocial-informed risk stratification tool to prevent suicides. Methods: A qualitative analysis of military suicides stationed at Fort Eustis, Virginia, using demographics from Fatality Review Boards (FRBs) of 10 cases assessing shared biopsychosocial stressors was conducted. The case reviews were used to assess the failure modes and effects analyses (FMEA), prompting the development of a performance improvement (PI) plan via a risk stratification scale that recognizes opportunities for intervention in the primary care and supervisor/peer settings to improve patient outcomes. Results: FMEA revealed the presence and interplay of multiple biopsychosocial stressors specifically impacting relationships, occupational functioning, financial status, legal issues, and undiagnosed mental health conditions across the 10 suicides reviewed. Furthermore, the severity of each stressor was best examined from a dimensional perspective to gauge the impact on or impairment of the individual in the military setting. The dimensional use of biopsychosocial stressors is congruent with our hypothesis that an increase in duration and intensity of biopsychosocial stressors increases risk of suicide. Conclusion: This case series reveals a gap in suicide assessment and suggests the use of a dimensional approach to measure biopsychosocial stressors at the entry level, such as primary care settings, or in the case of the military, during routine counseling. Additionally, a risk stratification tool that crosses biopsychosocial domains could provide a more accurate assessment for self-harm, in turn enabling a timely referral to appropriate helping agencies, including nonclinical resources.

Treatment of Hypoactive Sexual Desire Disorder Among Women: General Considerations and Pharmacological Options.

Hypoactive sexual desire disorder (HSDD) is a persistent or recurrent absence of sexual fantasies and desire for sexual activity, causing marked personal distress or interpersonal difficulties. HSDD affects 10% of U.S. women and is associated with depression and other negative emotional states. It is imperative that psychiatrists are competent to make this diagnosis and are aware of available treatment options. A full psychiatric and medical history are necessary to identify potential causes or contributing factors that may need to be addressed first. The authors discuss the diagnostic tools available as well as general diagnostic considerations for psychiatrists. Given its importance in the understanding of the available treatments for this disorder, the pathophysiology behind HSDD is reviewed. The authors emphasize the treatment of HSDD, including general treatment considerations, treatment in the context of depression, and psychotherapy and medications that have been approved by the U.S. Food and Drug Administration.