{"title":"Aerobic Exercise: Randomized Controlled Trial Data Suggest Qualified Benefits for Erectile Dysfunction.","authors":"Chittaranjan Andrade","doi":"10.4088/JCP.24f15480","DOIUrl":"https://doi.org/10.4088/JCP.24f15480","url":null,"abstract":"<p><p>Erectile dysfunction (ED) refers to the difficulty in achieving and maintaining a degree of penile erection that suffices for satisfactory sexual activity. ED is multifactorial in origin; its prevalence therefore varies with the population studied. In the general population, ED is present in 18-52% of men in younger to older age groups and in 43-76% of men with different medical conditions. Phosphodiesterase-5 inhibitor drugs are gold standard treatments for ED. However, because many lifestyle disorders predispose to ED and because aerobic exercise is beneficial for these lifestyle disorders, aerobic exercise may be a possible intervention for ED. In this context, a recent systematic review and meta-analysis identified 11 randomized controlled trials (RCTs; pooled N = 1,147) of aerobic exercise vs nonexercising control conditions for the treatment of ED. These RCTs had been conducted in men with different medical and surgical conditions, commonly obesity, metabolic syndrome, diabetes mellitus, and cardiovascular disease. The exercise interventions were varied but mostly involved 30-60 minutes sessions of activity, 3-5 times a week, for a median duration of 6 months. Advice for diet and weight loss was also commonly provided. The meta analysis found that aerobic exercise was significantly superior to nonexercising control conditions, with greater improvement in erectile functioning observed in subjects with greater baseline impairment. Limitations of the findings were that subjects could not be blinded to the nature of the intervention and that the magnitude of benefit with exercise, although statistically significant, fell below thresholds suggested for clinical significance. Aerobic exercise might therefore be more useful for the primary prevention of ED, for which preliminary evidence already exists. Exercise can also be recommended, along with other lifestyle guidance, to improve sexual functioning in both men and women and to improve health across a range of domains.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"85 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Learning by Doing: Can Our Collective Experiences as Clinicians Improve Mental Health Care?","authors":"A John Rush, Tony Tramontin","doi":"10.4088/JCP.24com15366","DOIUrl":"https://doi.org/10.4088/JCP.24com15366","url":null,"abstract":"","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"85 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Belén S Martín-Moreno, Julio Guija, Mario Blanco, Alejandro Porras-Segovia, Víctor Pereira-Sánchez, Enrique Baca-García, Lucas Giner
{"title":"Underdiagnosis, Undertreatment, and Noncompliance With Treatment in People Who Died by Suicide.","authors":"Belén S Martín-Moreno, Julio Guija, Mario Blanco, Alejandro Porras-Segovia, Víctor Pereira-Sánchez, Enrique Baca-García, Lucas Giner","doi":"10.4088/JCP.23m15182","DOIUrl":"10.4088/JCP.23m15182","url":null,"abstract":"<p><p><b>Background:</b> This study explored the characteristics of people who die by suicide, comparing those who had depression with those who did not.</p><p><p><b>Methods:</b> Clinical data were collected through a postmortem proxy-based semistructured interview (psychological autopsy). Postmortem toxicological analysis provides data on the presence of substances or drugs in the blood of suicides. Participants were adults who died by suicide in the province of Seville, Spain, during 2006-2016. The main independent variables were previous diagnosis, postmortem diagnosis, prescribed treatment, and treatment found in blood. The primary outcome was the postmortem diagnosis of depression, after which the sample was divided into 2 groups according to <i>DSM IV</i> criteria to the presence or absence of major depressive episode (MDE).</p><p><p><b>Results:</b> Our sample is composed of 313 people, of which 200 (63.9%) had a diagnosis of MDE according to the psychological autopsy. Predeath diagnosis of depression was more frequent in MDE suicides than in non-MDE suicides (18.6% vs 3.5%, respectively; <i>Χ</i><sup>2</sup> = 23.420; <i>df</i> = 9; <i>P</i> = .005) and had more access to mental health treatment previous to death (67.7% vs 35.6%, respectively; <i>Χ</i><sup>2</sup> = 27.572; <i>df</i> = 1; <i>P</i> < .001). Antidepressants were prescribed in 21.5% of the MDE suicides, but only 8.5% of them were taking them at the time of death according to the toxicology exam.</p><p><p><b>Conclusions:</b> The underdiagnosis of depression in people who die by suicide is striking, as is the undertreatment. Further efforts mu<b>s</b>t be made to train primary care physicians in the proper identification of persons at risk of suicide, as they are one of the main gatekeepers in the fight for suicide prevention.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"85 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samantha C Dashineau, Caroline E Balling, Susan C South, Mark Zimmerman
{"title":"Borderline Personality Disorder and Eating Disorders: Investigating the Role of Emotion Regulation.","authors":"Samantha C Dashineau, Caroline E Balling, Susan C South, Mark Zimmerman","doi":"10.4088/JCP.23m15152","DOIUrl":"https://doi.org/10.4088/JCP.23m15152","url":null,"abstract":"<p><p><b>Objective:</b> Borderline personality disorder (BPD) and eating disorders (EDs) both cause significant distress and co-occur at rates higher than expected, signifying potential overlapping regulatory mechanisms between both disorders. More specifically, both disorders involve emotion regulation deficits, suggesting they may share specific maladaptive regulatory components. The present study sought to examine the predictive role of emotion dysregulation within the comorbidity between EDs and BPD.</p><p><p><b>Methods:</b> A sample of psychiatric outpatients (N = 872) collected from a longitudinal study spanning the mid-1990s to 2015 completed the Structured Clinical Interview for <i>DSM-IV</i> for Axis I Disorders as well as a measure of emotion regulation strategies, the Difficulties in Emotion Regulation Scale, in order to assess overall functioning.</p><p><p><b>Results:</b> In a regression analysis, BPD was significantly predicted by emotion regulation deficits and was strongly related to categories of emotion dysregulation. EDs were not significantly predicted by emotion regulation deficits but did predict BPD diagnoses (B = -0.14, <i>P</i> < .001). Overall, BPD demonstrated strong relationships to emotion regulation deficits.</p><p><p><b>Conclusions:</b> Results indicate that targeted treatment focusing on emotion regulation deficits may be particularly indicated with co-occurring BPD and ED diagnoses.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"85 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epilepsy, Antiepileptic Drugs, and Adverse Pregnancy Outcomes, 2: Major Congenital Malformations With Antiepileptic Drug Monotherapy.","authors":"Chittaranjan Andrade","doi":"10.4088/JCP.24f15432","DOIUrl":"https://doi.org/10.4088/JCP.24f15432","url":null,"abstract":"<p><p>Women with epilepsy (WWE) are usually advised antiepileptic drug (AED) treatment even during pregnancy. It is therefore important to know what the major congenital malformation (MCM) risks might be with untreated epilepsy, and with first-trimester exposure to different AEDs in monotherapy. This article reviews recent findings from a large multinational registry, a large multinational population based study, and a large meta-analysis. In summary, data from the meta-analysis suggest that the MCM rate is 2%-3% in women without epilepsy and about 3% in WWE who were unexposed to AEDs during pregnancy. Data from the meta analysis also suggest that the MCM rate is approximately population level at 2.6%-3.5% with levetiracetam and lamotrigine and that it is about 4%-5% with carbamazepine, 2.8%-4.8% with oxcarbazepine, about 4% with topiramate, about 5%-7% with phenytoin, about 6%-9% with phenobarbital, and nearly 10% with valproate. The MCM risk with valproate is significantly higher than that with other AEDs (including topiramate and phenobarbital) that significantly increase the risk. Data from the registry suggest that risks are dose-dependent with valproate, phenobarbital, and carbamazepine and that the risk with valproate may be as high as 25% at doses >1,450 mg/d. Valproate is also associated with a wide range of MCMs. Data from the population-based study were generally confirmatory. Strengths and limitations of the studies are considered. The findings of these studies encourage the consideration of levetiracetam or lamotrigine monotherapy for WWE who are pregnant and strongly discourage the consideration of the older AEDs, especially phenytoin and phenobarbitone, and most especially valproate. These considerations also apply to all WWE of childbearing age because it may not be easy to change AEDs when pregnancy is planned and because pregnancy is often unplanned.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"85 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nidhi P Kulkarni, Mikaela K Dimick, Kody G Kennedy, David A Axelson, Dara J Sakolsky, Rasim S Diler, Danella M Hafeman, Tina R Goldstein, Kelly J Monk, Fangzi Liao, John A Merranko, Boris Birmaher, Benjamin I Goldstein
{"title":"Controlled Study of Metabolic Syndrome Among Offspring of Parents With Bipolar Disorder.","authors":"Nidhi P Kulkarni, Mikaela K Dimick, Kody G Kennedy, David A Axelson, Dara J Sakolsky, Rasim S Diler, Danella M Hafeman, Tina R Goldstein, Kelly J Monk, Fangzi Liao, John A Merranko, Boris Birmaher, Benjamin I Goldstein","doi":"10.4088/JCP.23m15058","DOIUrl":"https://doi.org/10.4088/JCP.23m15058","url":null,"abstract":"<p><p><b>Objectives:</b> Bipolar disorder (BD) is highly heritable and associated with increased rates of metabolic syndrome (MetS). However, little is known about MetS in offspring of parents with BD. We therefore examined this topic in the Pittsburgh Bipolar Offspring Study cohort.</p><p><p><b>Methods:</b> Participants included 199 parents (n = 116 BD, diagnosed using <i>DSM-IV</i>; n = 83 non-BD) and 330 offspring (mean age 19.9 ± 5.3 years), including 198 high-risk offspring of parents with BD (n = 80 affected with a mood disorder) and 132 control offspring. We defined MetS and its components using International Diabetes Federation (IDF) guidelines (primary) and National Cholesterol Education Program (NCEP) guidelines (secondary). Multivariable analyses controlled for age and socioeconomic status in offspring. Sensitivity analyses controlled for psychotropic medications.</p><p><p><b>Results:</b> There was higher prevalence of MetS in parents with BD as compared to controls. NCEP-defined MetS was significantly more prevalent among affected high-risk offspring (16.3%) and controls (15.2%) vs unaffected high-risk offspring (6.0%; χ<sup>2</sup> = 6.54, <i>P</i> = .04). There was greater mean number of MetS components (IDF: 1.7 ± 1.1; NCEP: 1.4 ± 1.0) among affected high-risk offspring vs unaffected high-risk offspring (IDF: 1.2 ± 1.0; NCEP: 1.0 ± 1.0) and controls (IDF: 1.3 ± 1.2; NCEP: 1.1 ± 1.1; IDF: <i>H</i>[2] = 10.26, <i>P =</i> .006; NCEP: <i>H</i>[2] = 9.18, <i>P =</i> .01). Most findings became nonsignificant in multivariable analyses. Some between-group results became nonsignificant after controlling for second-generation antipsychotics.</p><p><p><b>Conclusions:</b> This preliminary study found increased risk of MetS among affected high-risk offspring, which may be attributable to socioeconomic status. Prospective studies may determine timing of MetS onset in relation to mood disorder onset, and the role of socioeconomic status in moderating this association.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"85 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sindhura Vangala, Roy Williams, Cara M Buskmiller, Jessian L Munoz
{"title":"Mental Health Assessments for Fetal Interventions.","authors":"Sindhura Vangala, Roy Williams, Cara M Buskmiller, Jessian L Munoz","doi":"10.4088/JCP.24l15275","DOIUrl":"https://doi.org/10.4088/JCP.24l15275","url":null,"abstract":"","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"85 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mina M Rizk, Lindsay Bolton, Flurin Cathomas, Helen He, Scott J Russo, Emma Guttman-Yassky, J John Mann, James Murrough
{"title":"Immune-Targeted Therapies for Depression: Current Evidence for Antidepressant Effects of Monoclonal Antibodies.","authors":"Mina M Rizk, Lindsay Bolton, Flurin Cathomas, Helen He, Scott J Russo, Emma Guttman-Yassky, J John Mann, James Murrough","doi":"10.4088/JCP.23nr15243","DOIUrl":"10.4088/JCP.23nr15243","url":null,"abstract":"<p><p><b>Importance:</b> Increasing evidence suggests a potential role of immune-modulatory drugs for treatment-resistant depression. This scoping review explores the emerging evidence regarding the antidepressant effects of monoclonal antibodies (mAbs), a relatively newer class of immune therapeutics with favorable safety profile.</p><p><p><b>Observations:</b> PubMed was searched up to November 2023 for English publications addressing the antidepressant effects of mAbs, including meta-analyses, randomized controlled trials, open-label, single-arm studies, and case series. Several mAbs have shown potential antidepressant effects, but most studies in primary inflammatory disorders included patients with mild depression. Only infliximab and sirukumab were directly examined in individuals with primary depression. mAbs that do not require laboratory monitoring, such as ixekizumab and dupilumab, could hold potential promise if future studies establish their safety profile regarding suicide risk.</p><p><p><b>Conclusions and Relevance:</b> The use of several mAbs for the treatment of primary inflammatory disorders has been associated with improvement of comorbid depressive symptoms. Given their unique mechanisms of action, mAbs may offer a new hope for depressed patients who do not respond to currently available antidepressants. Further research addressing individuals with more severe depressive symptoms is essential. Direct examination of antidepressant effects of mAbs in people with primary depressive disorders is also crucial to refine their clinical use in the treatment of depression.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"85 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dianying Liu, Gang Lei, Dian Li, Hongdong Deng, Xiang Yang Zhang, Yonghui Dang
{"title":"Depression, Rumination, and Suicide Attempts in Adolescents With Mood Disorders: Sex Differences in This Relationship.","authors":"Dianying Liu, Gang Lei, Dian Li, Hongdong Deng, Xiang Yang Zhang, Yonghui Dang","doi":"10.4088/JCP.23m15136","DOIUrl":"https://doi.org/10.4088/JCP.23m15136","url":null,"abstract":"<p><p><b>Abstract</b>.</p><p><p><b>Background:</b> Sex differences in suicide attempts have been widely recognized across domains such as depression and rumination. The relationship between depression, rumination, and suicide attempts in mood disorders has been studied before; however, how they interact across sexes remains unclear. This study aimed to examine the sex differences in the relationship between depression, rumination, and suicide attempts in Chinese adolescents with mood disorders.</p><p><p><b>Methods:</b> We recruited 681 adolescents with mood disorders who met ICD-10 criteria for having unipolar or bipolar depression with a current depressive episode at the time of the study and collected demographic and clinical data.</p><p><p><b>Results:</b> The prevalence of suicide attempts in female adolescents with mood disorders (64.36%) was significantly higher than that in male adolescents with mood disorders (49.47%), with an odds ratio of 1.84 (95% CI, 1.31-2.59). Regression analysis showed that PHQ-9 was independently associated with suicide attempts among male adolescents with mood disorders, while in female adolescents with mood disorders, total scores of PHQ-9 and RRS-10 were independently associated with suicide attempts. Importantly, in female adolescents with mood disorders, the mediating effect of RRS-10 total score on the relationship between PHQ-9 and suicide attempts was significant (standardized β = 0.005, <i>P</i> = 0.003, 95% CI, 0.002-0.008), the mediating effect accounted for 31.25% of the total effect of depressive symptoms on suicide attempts.</p><p><p><b>Conclusions:</b> Our study suggests that there are sex differences in depression, rumination, and suicide attempts and in the interaction between them in adolescents with mood disorders. These sex differences may have important clinical implications, both for improving strategies to detect suicidal behaviors and for developing better early intervention programs for this population.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"85 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maurizio Fava, Stephen M Stahl, Luca Pani, Sara De Martin, Andrew J Cutler, Vladimir Maletic, Charles W Gorodetzky, Frank J Vocci, Frank L Sapienza, Thomas R Kosten, Cornelia Kröger, Paggard Champasa, Cedric O'Gorman, Clotilde Guidetti, Andrea Alimonti, Stefano Comai, Andrea Mattarei, Franco Folli, David Bushnell, Sergio Traversa, Charles E Inturrisi, Paolo L Manfredi, Marco Pappagallo
{"title":"Efficacy and Safety of Esmethadone (REL-1017) in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants: A Phase 3 Randomized Controlled Trial.","authors":"Maurizio Fava, Stephen M Stahl, Luca Pani, Sara De Martin, Andrew J Cutler, Vladimir Maletic, Charles W Gorodetzky, Frank J Vocci, Frank L Sapienza, Thomas R Kosten, Cornelia Kröger, Paggard Champasa, Cedric O'Gorman, Clotilde Guidetti, Andrea Alimonti, Stefano Comai, Andrea Mattarei, Franco Folli, David Bushnell, Sergio Traversa, Charles E Inturrisi, Paolo L Manfredi, Marco Pappagallo","doi":"10.4088/JCP.24m15265","DOIUrl":"10.4088/JCP.24m15265","url":null,"abstract":"<p><p><b>Objective:</b> To test esmethadone (REL-1017) as adjunctive treatment in patients with major depressive disorder (MDD) and inadequate response to standard antidepressants.</p><p><p><b>Methods:</b> In this phase 3, double-blind, placebo-controlled trial, outpatients with MDD (<i>DSM-5</i>) were randomized to daily oral esmethadone (75 mg on day 1, followed by 25 mg daily on days 2 through 28) or placebo between December 2020 and December 2022. The primary efficacy measure was change from baseline (CFB) to day 28 in the Montgomery-Asberg Depression Rating Scale (MADRS) score. The intent-to-treat (ITT) population included all randomized participants. The per-protocol (PP) population included completers without major protocol deviations impacting assessment. Post hoc analyses included participants with severe depression (baseline MADRS score ≥35).</p><p><p><b>Results:</b> For the ITT analysis (n = 227), mean CFB was 15.1 (SD 11.3) for esmethadone (n = 113) and 12.9 (SD 10.4) for placebo (n = 114), with a mean difference (MD) of 2.3, which was not statistically significant (<i>P</i> = .154; Cohen effect size [ES] = 0.21). Remission rates were 22.1% and 13.2% (<i>P</i> = .076), and response rates were 39.8% and 27.2% (<i>P</i> = .044) with esmethadone and placebo, respectively. For the PP analysis (n = 198), mean CFB was 15.6 (SD 11.2) for esmethadone (n = 101) and 12.5 (SD 9.9) for placebo (n = 97), with an MD of 3.1 (<i>P</i> = .051; ES =0.29). In post hoc analyses of patients with baseline MADRS ≥35 in the ITT population (n = 112), MD was 6.9; <i>P</i> = .0059; ES = 0.57, and for the PP population (n = 98), MD was 7.9; <i>P</i> = .0015; ES = 0.69. Adverse events (AEs) were predominantly mild or moderate and transient, with no significant differences between groups.</p><p><p><b>Conclusions:</b> The primary end point was not met. Esmethadone showed stronger efficacy in PP than in ITT analyses, with the discrepancy not attributable to AEs impacting treatment adherence. Significant efficacy occurred in post hoc analyses of patients with severe depression. Esmethadone was well tolerated, consistent with prior studies.</p><p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT04688164.</p>","PeriodicalId":50234,"journal":{"name":"Journal of Clinical Psychiatry","volume":"85 3","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}