Perception of gender disparity in academic reproductive endocrinology and infertility.

The aim of this study was to identify gender differences in leadership/academic rank and attitudes regarding gender representation among academic Reproductive Endocrinology and Infertility subspecialists. Members of the Society of Reproductive Endocrinology and Infertility (SREI) were surveyed regarding gender, academic rank, and attitudes concerning gender disparity in academic medicine in March 2021. Univariate comparisons were performed using Chi-squared and Fischer-exact tests with significance at p ≤ 0.05. A total of 237 SREI members completed the survey with a response rate of 28.8%. Of those, 176 practiced in academic medicine. The majority (76.7%) have been in practice for greater than 10 years. The female-to-male ratio changed over time with ratios of 1.1:1 for those in practice over 10 years and 5.8:1 for those less than 10 years. Of providers in practice greater than 10 years, there were significantly more male vs. female full professors (72.3% vs. 48.5%, p < 0.01), less frequent male assistant professors (3% vs.17%, p < 0.01) and a similar percentage of male and female associate professors (24.6% vs. 34.3%, p = 0.2). Among those in practice for less than 10 years, there were no differences in academic rank between males and females. When stratified by years in practice, there was no difference in gender among division directors, fellowship directors, or assistant/associate fellowship directors. 68.2% of respondents believe there is a gender disparity in academic rank, with females more likely to have this opinion (79% vs. 52.1%, p < 0.001). The female-to-male ratio in academic REI has dramatically changed with time. Even with this shift, the majority of providers believe in a gender disparity regarding academic rank that is due to systemic factors limiting the academic advancement of females. When stratified by years in practice, women in practice greater than 10 years were less likely to hold the rank of full professor than men despite equal leadership positions.

Survey assessing policies regarding patient age and provision of fertility treatment in the United States.

PURPOSE: To determine what policies exist regarding age and provision of fertility treatment in United States fertility clinics. METHODS: Medical directors of the Society for Assisted Reproductive Technology (SART) member clinics were surveyed regarding clinic demographics and current policies pertaining to age and provision of fertility treatment. Univariate comparisons were performed using Chi-square and Fisher exact tests as appropriate, with significance set at P ≤ 0.05. RESULTS: Of the 366 clinics surveyed, 18.9% (69/366) responded. A majority of clinics who responded 88.4% (61/69) reported having a policy regarding patient age and provision of fertility treatment. Responding clinics with an age policy did not differ from those without a policy on the basis of geographical location, (p = 0.5), insurance mandate status (p = 0.9), practice type (p = 0.4), or annual number of ART cycles (p = 0.7). Of all clinics who responded, 73.9% (51/69) had a maximum maternal age for autologous IVF, with a median of 45 years (range 42-54). Similarly, 79.7% (55/69) of responding clinics had a maximum maternal age for donor oocyte IVF, with a median of 52 years (range 48-56). Slightly under half, 43.4% (30/69) of responding clinics had a maximum maternal age for fertility treatment other than IVF (including ovulation induction or ovarian stimulation with or without IUI) with a median of 46 years (range 42-55). Of note, only 4.3% (3/69) of responding clinics had a policy with respect to maximum paternal age, with a median of 55 years (range 55-70). The most commonly cited reasons for having an age-limit policy were maternal risks of pregnancy, lower ART success rates, fetal/neonatal risks, and concerns about patients' ability to parent at an older age. More than half 56.5% (39/69) of responding clinics reported making exceptions to these policies, most commonly for patients who have pre-existing embryos. The majority of medical directors who responded to the survey believed there should be an ASRM guideline regarding maximum maternal age for autologous IVF 71% (49/69), donor oocyte IVF 78% (54/69) and other fertility treatments 62% (43/69). CONCLUSIONS: Most fertility clinics who responded to this national survey reported having a policy regarding maternal age (but not paternal age) and provision of fertility treatment. Policies were based on risk of maternal/fetal complications, lower success rates at older age, and concerns about patients' ability to parent at an older age. The majority of medical directors of responding clinics believed there should be an ASRM guideline regarding age and provision of fertility treatment.

Direct-to-consumer fertility testing: utilization and perceived utility among fertility patients and reproductive endocrinologists.

RESEARCH QUESTION: What is the utilization of direct-to-consumer fertility tests (DTCFT) among fertility patients? How does the perceived utility of DTCFT differ between patients and reproductive endocrinologists (REI)? DESIGN: Infertility patients visiting the Duke Fertility Center between December 2020 and December 2021 were sent an electronic invitation to participate in a patient survey. Members of the Society of Reproductive Endocrinology and Infertility were also sent e-mail invitations to participate in the REI survey. DTCFT were defined as tests not ordered by a physician or performed at a physician's office, including calendar methods of ovulation prediction, urinary ovulation prediction kits, basal body temperature (BBT) monitoring, hormone analysis, ovarian reserve testing and semen analysis. Patients and REI were asked how likely they were to recommend a given DTCFT, on a 0-10 Likert scale. RESULTS: In total, 425 patients (response rate 50.5%) and 178 REI (response rate 21.4%) completed the surveys. Patients reported the utilization of calendar methods of ovulation prediction (83.8%), urinary ovulation prediction (78.8%), BBT monitoring (30.8%), hormone analysis (15.3%), semen analysis (10.1%) and ovarian reserve testing (9.2%). REI rated the utility of all DTCFT significantly lower than patients did (average discordance -4.2, P < 0.001), except for urinary ovulation prediction, which REI gave a significantly higher score (discordance +1.0, P < 0.001). Prior pregnancy was significantly associated with home ovulation prediction utilization among patients (adjusted odds ratio 3.21, 95% confidence interval 1.2-9.83). CONCLUSIONS: Methods of ovulation prediction are commonly used by fertility patients. Significant discordance exists in the perceived utility of DTCFT between patients and REI. Patient education and guidelines are needed to better inform individuals considering DTCFT.

Reproductive Functions of the Mitochondrial Progesterone Receptor (PR-M).

Classic transcriptional regulation by progesterone via the nuclear progesterone receptors A and B (PR-A, PR-B) has been recognized for decades. Less attention has been given to a mitochondrial progesterone receptor (PR-M) responsible for non-nuclear activities. PR-M is derived from the progesterone receptor (PR) gene from an alternate promoter with the cDNA encoding a unique 5' membrane binding domain followed by the same hinge and hormone-binding domain of the nPR. The protein binds to the mitochondrial outer membrane and functions to increase cellular respiration via increased beta-oxidation and oxidative phosphorylation with resulting adenosine triphosphate (ATP) production. Physiologic activities of PR-M have been studied in cardiac function, spermatozoa activation, and myometrial growth, all known to respond to progesterone. Progesterone via PR-M increases cardiomyocyte cellular respiration to meet the metabolic demands of pregnancy with increased contractility. Consequential gene changes associated with PR-M activation include production of proteins for sarcomere development and for fatty acid oxidation. Regarding spermatozoa function, progesterone via PR-M increases cellular energy production necessary for progesterone-dependent hyperactivation. A role of progesterone in myometrial and leiomyomata growth may also be explained by the increase in necessary cellular energy for proliferation. Lastly, the multi-organ increase in cellular respiration may contribute to the progesterone-dependent increase in metabolic rate reflected by an increase in body temperature through compensatory non-shivering thermogenesis. An evolutionary comparison shows PR-M expressed in humans, apes, and Old World monkeys, but the necessary gene sequence is absent in New World monkeys and lower species. The evolutionary advantage to PR-M remains to be defined, but its presence may enhance catabolism to support the extended gestation and brain development found in these primates.

Use of fertility preservation services in male reproductive-aged cancer patients.

While fertility preservation is a major concern among reproductive age cancer patients, little is known about access and use of fertility preserving services. We examined use of fertility preserving services among men with common solid tumors. A total of 3648 men age 18-40 including 2610 (71.6%) with testicular cancer, 939 (25.7%) with colorectal and 99 (2.7%) with prostate cancer were identified. Fertility preservation services were utilized in 9.3% of men overall including 4.1% who underwent fertility evaluation only and 7.8% who had a fertility preservation procedure. The rate of fertility preservation services rose from 6.6% (95%CI, 3.2-10.0) in 2008 to 12.4% (95%CI, 7.3-17.5) in 2017 (P = 0.04). Use of fertility preservation service was more common in patients with testicular (11.6%, aRR = 3.31; 95% CI 2.22-4.92) and prostate cancer (6.1%, aRR = 3.14; 95% CI 1.28-7.70) compared to those with colon cancer (3.4%). Younger men were more likely to utilize fertility preservation services. 11.5% of men age ≤ 35 years vs. 5.2% of men 36-40 used these services (P < 0.0001). Fertility preservation services were used in 10.8% of those who received chemotherapy (aRR = 1.81; 95% CI, 1.45-2.27) and in 8.1% of those who received radiation (aRR = 1.30 95% CI, 0.98-1.73). Medicaid patients were less likely to receive fertility preservation services than those with commercial insurance (0.7% vs. 10.1%; aRR = 11.58, 95%CI 2.10-63.69). These data indicate that while use of fertility preserving services is increasing, overall use of services is low among reproductive age males with cancer.

Gender inequality in leadership and academic rank in academic reproductive endocrinology programs.

PURPOSE: To identify gender differences in leadership and academic rank within academic reproductive endocrinology (REI) programs with fellowships in the USA. METHODS: Official institutional websites of the 2017-2018 American Board of Obstetrics and Gynecology (ABOG)-accredited reproductive endocrinology fellowship programs were reviewed, and gender representation at each leadership position and academic rank (Division and Fellowship Director and Full, Associate, and Assistant Professor) was recorded. Univariate comparisons were performed using Chi-square tests, with significance at p < 0.05. RESULTS: Among 49 ABOG-accredited reproductive endocrinology programs, 263 faculty were identified, 129 (49.0%) male and 134 (51.0%) female. Division directors were 69.3% male and 30.7% female (p = 0.006). Similarly, fellowship directors were 65.3% male and 34.6% female (p = 0.03). Full professors (n = 101) were more frequently male (70.3% vs. 29.7%, p < 0.001). There was no difference in gender among associate professors (n = 60, 51.7% male vs. 48.3% female, p = 0.79), while significantly more assistant professors were female than male (n = 102, 73.6% vs. 26.4%, p < 0.001). CONCLUSION: While a majority of residents in obstetrics and gynecology and half of reproductive endocrinology academic faculty are female, women are still underrepresented among leadership positions and full professors in academic reproductive endocrinology programs with fellowship programs.

Cost-Benefit Analysis of a Support Program for Nursing Staff.

OBJECTIVES: A peer-support program called Resilience In Stressful Events (RISE) was designed to help hospital staff cope with stressful patient-related events. The aim of this study was to evaluate the impact of the RISE program by conducting an economic evaluation of its cost benefit. METHODS: A Markov model with a 1-year time horizon was developed to compare the cost benefit with and without the RISE program from a provider (hospital) perspective. Nursing staff who used the RISE program between 2015 and 2016 at a 1000-bed, private hospital in the United States were included in the analysis. The cost of running the RISE program, nurse turnover, and nurse time off were modeled. Data on costs were obtained from literature review and hospital data. Probabilities of quitting or taking time off with or without the RISE program were estimated using survey data. Net monetary benefit (NMB) and budget impact of having the RISE program were computed to determine cost benefit to the hospital. RESULTS: Expected model results of the RISE program found a net monetary benefit savings of US $22,576.05 per nurse who initiated a RISE call. These savings were determined to be 99.9% consistent on the basis of a probabilistic sensitivity analysis. The budget impact analysis revealed that a hospital could save US $1.81 million each year because of the RISE program. CONCLUSIONS: The RISE program resulted in substantial cost savings to the hospital. Hospitals should be encouraged by these findings to implement institution-wide support programs for medical staff, based on a high demand for this type of service and the potential for cost savings.

Use of fertility preservation services in female reproductive-aged cancer patients.

OBJECTIVE: The objective of the study was to determine the rates and predictors of fertility preservation services among reproductive-aged women with common cancers in the United States. STUDY DESIGN: We used the MarketScan database to identify women 18-45 years of age with lung, breast, colorectal, or cervical cancer who underwent surgery and chemotherapy from 2009 through 2016. Services from 3 months before to 3 months after chemotherapy for evaluation for fertility preservation, laboratory testing for fertility evaluation, and fertility-preserving procedures were captured. Multivariable models were used to assess the factors associated with the use of fertility-preservation services. RESULTS: A total of 18,781 women, including 386 cervical, 1372 colorectal, 246 lung, and 16,777 with breast cancer, were identified. In women 18-35 years old, 11.7% underwent evaluation for fertility preservation, 13.7% underwent laboratory testing, and 6.3% pursued fertility-preserving procedures. The rates of office evaluation, laboratory testing, and performance of procedure were 3.3%, 7.5%, and 1.9 % in women aged 36-40 years and 0.5%, 7.2%, and 0.3% in those aged 41-45 years, respectively. The rate of fertility preservation evaluation rose from 1.0% in 2009 to 5.5% in 2016 (risk ratio, 4.66, 95% confidence interval, 2.38-9.11) while use of fertility-preserving procedures increased from 1.0% to 4.6% (risk ratio, 3.84, 95% confidence interval, 1.94-7.59) during the same time period. In a multivariable model, use of any fertility-preserving interventions were more common in patients with breast cancer (adjusted risk ratio, 2.30, 95% confidence interval, 1.30-4.06), those in the Northeast (adjusted risk ratio, 1.24, 95% confidence interval, 1.10-1.40), and in younger women (18-35 years) (adjusted risk ratio, 2.59, 95% confidence interval, 2.32-2.89). CONCLUSION: Although limited by lack of information regarding cancer stage and desire for future fertility, only a small fraction of reproductive-aged female cancer patients receiving chemotherapy are evaluated in a nationwide sample for fertility preservation or undergo fertility-preserving procedures.

Life-threatening complications among women with severe ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome is a potentially life-threatening clinical condition. OBJECTIVE: The objective of this study was to evaluate risk factors for life-threatening complications for patients with severe ovarian hyperstimulation syndrome in a United States nationwide sample. MATERIALS AND METHODS: Ovarian hyperstimulation syndrome admissions from 2002 to 2011 from the Nationwide Inpatient Sample were included in this study. The association between patient and hospital factors and life-threatening complications (deep vein thrombosis/pulmonary embolism, acute respiratory distress syndrome, acute renal failure, intubation), nonroutine discharge (discharge to skilled nursing facility, transfer hospital), prolonged length of stay, and total hospital charges were analyzed. Survey-adjusted multivariable logistic regression analyses were performed for these outcomes, controlling for risk factors, with adjusted odds ratios with 95% confidence intervals as the measures of effect. RESULTS: A total of 11,562 patients were hospitalized with severe ovarian hyperstimulation syndrome from 2002 to 2011. The majority were white (55.7%), with private insurance (87.7%), aged 25-39 years (84.6%), and hospitalized in an urban location (95%). In all, 19.3% of patients had medical comorbidities including hypertension, diabetes, obesity, hypothyroidism, and anemia. Life-threatening complications occurred in 4.4% of patients (deep vein thrombosis/pulmonary embolism, 2.2%; acute renal failure; acute respiratory distress syndrome, 0.9%; intubation, 0.5%). Patients ≥40 years old (odds ratio, 4.02; 95% confidence interval, 1.37, 11.76), those with comorbidities (odds ratio, 2.29; 95% confidence interval, 1.46, 3.57), and African American patients (odds ratio, 2.15; 95% confidence interval, 1.25, 3.70) were more likely to develop life-threatening conditions. Patients with medical comorbidities (odds ratio, 0.39; 95% confidence interval, 0.24, 0.63) were also less likely to be routinely discharged from the hospital. Adjusting for patient and hospital demographics, patients with comorbidities were more likely to develop deep vein thrombosis/pulmonary embolism (adjusted odds ratio, 2.44; 95% confidence interval, 1.28, 4.65) and acute renal failure (adjusted odds ratio, 2.26; 95% confidence interval, 1.21, 4.23). Patients who developed life-threatening complications had longer hospital length of stay (adjusted odds ratio, 3.72; 95% confidence interval, 2.28, 6.07) and higher hospital costs (adjusted odds ratio, 5.20; 95% confidence interval, 3.22,8.39). CONCLUSION: Patients with common medical comorbidities are at higher risk for life-threatening complications in the setting of severe ovarian hyperstimulation syndrome. Furthermore, these complications are associated with high hospital costs and hospital burden. Given the increasing number of in vitro fertilization patients with medical comorbidities, closer monitoring of at-risk patients may be indicated. As assisted reproductive technology practice changes in recent years with strategies designed to reduce ovarian hyperstimulation syndrome risk, future studies are needed to assess the impact of these changes on hospitalization and complication risk.

Lesbian, gay, bisexual, transgender content on reproductive endocrinology and infertility clinic websites.

OBJECTIVE: To assess geographical distribution and practice characteristics of fertility clinics inclusive of lesbian, gay, bisexual, and transgender (LGBT) patients. DESIGN: Cross-sectional analysis. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prevalence and geographical distribution of fertility clinic websites with LGBT-specific content, indicated by keywords and home page cues specific to the LGBT patient population. Assessment of relationship between LGBT-specific content and clinic characteristics, including U.S. region, clinic size, private versus academic setting, and state-mandated fertility insurance coverage. RESULT(S): Of 379 websites analyzed, 201 (53%) contained LGBT content. Clinics with the highest proportion of LGBT website content were in the Northeast (59/82, 72%) and West (63/96, 66%), while the lowest proportion was in the Midwest (29/74, 39%) and South (50/127, 39%). Most frequently used terms included lesbian (72%), LGBT/LGBTQ (69%), and gay (68%), while less used terms included trans/transgender (32%) and bisexual (15%). Larger clinic size was associated with LGBT-specific website content (odds ratio, 4.42; 95% confidence interval, 2.07-9.67). Practice type and state-mandated fertility insurance coverage were not associated with a clinic website having LGBT content. CONCLUSION(S): Over half of Society for Assisted Reproductive Technology member fertility clinics included LGBT content on their websites, yet those in the Midwest and South were significantly less likely to do so. Predictive factors for having LGBT website content included location in northeastern and western regions and increasing clinic size. Further studies are needed to evaluate whether inclusion of LGBT content on clinic websites impacts use of reproductive services by the LGBT patient population.

Hydronephrosis: A Rare Presentation of Uterine Didelphys with Obstructed Hemivagina and Ipsilateral Renal Anomaly.

BACKGROUND: Obstructed hemivagina and ipsilateral renal anomaly syndrome is a Müllerian duct anomaly characterized by uterine didelphys, obstructed hemivagina, and ipsilateral renal anomalies. CASE: A 12-year-old girl with a history of right renal agenesis presented to the emergency department with abdominal pain, dysuria, and urinary retention. Imaging identified a uterine didelphys with a large obstructed right hemivagina compressing the left ureter, causing hydronephrosis. She underwent vaginal septum resection for curative treatment. SUMMARY AND CONCLUSION: In female patients who present with abdominal pain and a history of renal abnormalities, obstructed hemivagina and ipsilateral renal anomaly syndrome must be considered in the differential diagnosis. This consideration is important in preventing complications such as hydronephrosis seen in this patient.

In Vitro Activation: A Possible New Frontier for Treatment of Primary Ovarian Insufficiency.

In vitro activation (IVA) represents a new frontier in the treatment of women with primary ovarian insufficiency as well as patients with cancer desiring fertility preservation. Here, we review the biological basis of IVA and the recent translation of IVA to humans by targeting Hippo and Akt-signaling pathways. We then provide a new integrated viewpoint on IVA, highlighting basic science research on the aspects of follicular development and ovarian tissue transplantation which may potentially optimize future translational research on IVA. Specific topics discussed include cryopreservation techniques, additional IVA pathway targets, the roles of actin polymerization, paracrine and endocrine factors, and the role of mechanical signaling and associated tissue rigidity in controlling ovarian follicular activation. Further research and improved understanding is needed to optimize success of IVA.

The relationship between Graves' ophthalmopathy and dry eye syndrome.

BACKGROUND: A complex relationship between Graves' ophthalmopathy (GO) and dry eye syndrome exists. New research brings more insight into the association between these two diseases. METHODS: A review of the literature was conducted using the query terms "Graves' Ophthalmopathy", "Thyroid Eye Disease", and "Dry Eye" in MedLine (PubMed) and Scopus. A total of 55 papers were reviewed. Case reports were excluded. CONCLUSION: This review paper shows the close relationship between dry eye syndrome and GO. The underlying mechanisms behind their association suggest mechanical impairment of orbital muscles and immune-mediated lacrimal gland dysfunction as the causes of dry eye in GO patients. However, there are a variety of treatment options available for patients with GO with signs of dry eye, which help combat this issue.

Dietary and medication adjustments to improve seizure control in patients treated with the ketogenic diet.

Unlike anticonvulsant drugs and vagus nerve stimulation, there are no guidelines regarding adjustments to ketogenic diet regimens to improve seizure efficacy once the diet has been started. A retrospective chart review was performed of 200 consecutive patients treated with the ketogenic diet at Johns Hopkins Hospital from 2007 to 2013. Ten dietary and supplement changes were identified, along with anticonvulsant adjustments. A total of 391 distinct interventions occurred, of which 265 were made specifically to improve seizure control. Adjustments led to >50% further seizure reduction in 18%, but only 3% became seizure-free. The benefits of interventions did not decrease over time. There was a trend towards medication adjustments being more successful than dietary modifications (24% vs 15%, P = .08). No single dietary change stood out as the most effective, but calorie changes were largely unhelpful (10% with additional benefit).

Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder.

The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD). In rats, ketamine selectively increased electroencephalogram (EEG) slow wave activity (SWA) during non-rapid eye movement (REM) sleep and altered central brain-derived neurotrophic factor (BDNF) expression. Taken together, these findings suggest that higher SWA and BDNF levels may respectively represent electrophysiological and molecular correlates of mood improvement following ketamine treatment. This study investigated the acute effects of a single ketamine infusion on depressive symptoms, EEG SWA, individual slow wave parameters (surrogate markers of central synaptic plasticity) and plasma BDNF (a peripheral marker of plasticity) in 30 patients with treatment-resistant MDD. Montgomery-Åsberg Depression Rating Scale scores rapidly decreased following ketamine. Compared to baseline, BDNF levels and early sleep SWA (during the first non-REM episode) increased after ketamine. The occurrence of high amplitude waves increased during early sleep, accompanied by an increase in slow wave slope, consistent with increased synaptic strength. Changes in BDNF levels were proportional to changes in EEG parameters. Intriguingly, this link was present only in patients who responded to ketamine treatment, suggesting that enhanced synaptic plasticity - as reflected by increased SWA, individual slow wave parameters and plasma BDNF - is part of the physiological mechanism underlying the rapid antidepressant effects of NMDA antagonists. Further studies are required to confirm the link found here between behavioural and synaptic changes, as well as to test the reliability of these central and peripheral biomarkers of rapid antidepressant response.

Baseline delta sleep ratio predicts acute ketamine mood response in major depressive disorder.

BACKGROUND: Electroencephalographic (EEG) sleep slow wave activity (SWA; EEG power between 0.6 and 4Hz) has been proposed as a marker of central synaptic plasticity. Decreased generation of sleep slow waves--a core feature of sleep in depression--indicates underlying plasticity changes in the disease. Various measures of SWA have previously been used to predict antidepressant treatment response. This study examined the relationship between baseline patterns of SWA in the first two NREM episodes and antidepressant response to an acute infusion of the N-methyl-d-aspartate (NMDA) antagonist ketamine. METHODS: Thirty patients (20M, 10F, 18-65) fulfilling DSM-IV criteria for treatment-resistant major depressive disorder (MDD) who had been drug-free for two weeks received a single open-label infusion of ketamine hydrochloride (.5mg/kg) over 40 min. Depressive symptoms were assessed with the Montgomery-Asberg Depression Rating Scale (MADRS) before and after ketamine infusion. Sleep recordings were obtained the night before the infusion and were visually scored. SWA was computed for individual artifact-free NREM sleep epochs, and averaged for each NREM episode. Delta sleep ratio (DSR) was calculated as SWA(NREM1)/SWA(NREM2). RESULTS: A significant positive correlation was observed between baseline DSR and reduced MADRS scores from baseline to Day 1 (r=.414, p=.02). LIMITATIONS: The sample size was relatively small (N=30) and all subjects had treatment-resistant MDD, which may limit the generalizability of the findings. Further studies are needed to replicate and extend this observation to other patient groups. CONCLUSIONS: DSR may be a useful baseline predictor of ketamine response in individuals with treatment-resistant MDD.

Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial.

BACKGROUND: Currently, no pharmacological treatments for bipolar depression exist that exert rapid (within hours) antidepressant or antisuicidal effects. We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. The present study sought to replicate this finding in an independent sample. METHODS: In this double-blind, randomized, crossover, placebo-controlled study, 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate received a single intravenous infusion of either ketamine hydrochloride (.5 mg/kg) or placebo on 2 test days 2 weeks apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline; at 40, 80, 110, and 230 minutes postinfusion; and on days 1, 2, 3, 7, 10, and 14 postinfusion. RESULTS: Within 40 minutes, depressive symptoms, as well as suicidal ideation, significantly improved in subjects receiving ketamine compared with placebo (d = .89, 95% confidence interval = .61-1.16, and .98, 95% confidence interval = .64-1.33, respectively); this improvement remained significant through day 3. Seventy-nine percent of subjects responded to ketamine and 0% responded to placebo at some point during the trial. The most common side effect was dissociative symptoms, which occurred only at the 40-minute time point. CONCLUSIONS: This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response. In addition, we found that ketamine rapidly improved suicidal ideation in these patients.