Journal of Clinical Psychiatry最新文献

Objective: This post hoc analysis of the ESCAPE-TRD trial compared work productivity loss (WPL) and related costs among patients with treatment-resistant depression (TRD) receiving esketamine nasal spray or quetiapine extended release in combination with an oral antidepressant.

Methods: Adults with TRD randomized to receive esketamine (56/84 mg) or quetiapine (150-300 mg) combined with ongoing antidepressant therapy were included. WPL was assessed using the Work Productivity and Activity Impairment questionnaire. Least squares (LS) mean WPL change versus baseline (treatment initiation date), and LS mean differences (MDs) between esketamine and quetiapine cohorts were reported at weeks 8-32 of treatment using mixed models for repeated measurements. Per patient productivity cost savings were estimated using mean 2021 weekly wages from US Bureau of Labor Statistics.

Results: The esketamine cohort included 165 patients, and quetiapine cohort included 156 patients. At baseline, total WPL was 77.0% and 72.5% in the esketamine and quetiapine cohorts, respectively. By week 8, total WPL decreased from baseline by 30.3 and 17.3 percentage points (pp) in the esketamine and quetiapine cohorts (MD = 13.0 pp; 95% confidence interval [CI], 6.3-19.8 pp), resulting in weekly cost savings of $363 and $207 (MD = $156; 95% CI, $76-$237), respectively. By week 32, total WPL decreased from baseline by 45.3 pp and 32.5 pp in the esketamine and quetiapine cohorts (MD = 12.7 pp; 95% CI, 4.7-20.7 pp), with weekly cost savings of $543 and $390 (MD = $153; 95% CI, $57-$250), respectively.

Conclusion: Among employed adults with TRD, esketamine treatment was associated with significantly larger improvements in WPL and related costs compared to quetiapine, suggesting greater benefits from patient well-being and employer perspectives.

Background: The COVID-19 pandemic was an unprecedented global health crisis. Vulnerable populations with preexisting mental illness have been disproportionately burdened and may experience adverse mental health outcomes related to the COVID-19 pandemic.

Objectives: Our objective was to evaluate the association between COVID-19 diagnosis, known exposure to COVID-19, sheltering in place, symptom severity, psychological distress, and depression severity among adults with severe mental illness (SMI).

Methods: In a cross-sectional study, participants were recruited among patients with SMI who visited an urban community health center in Georgia between February 1, 2019, and March 11, 2021. Measures included COVID-19 impacts on the symptoms of schizophrenia and other psychotic disorders, and severe mood disorders with psychotic features, depression symptoms, self-reported psychological distress, and social connectedness.

Results: Adults diagnosed with COVID-19 experienced more severe psychological distress (odds ratio [OR] = 2.48, 95% CI, 1.02-6.28) compared to those not diagnosed with COVID-19. After adjusting for sex and age, adults with SMI who sheltered in place during the lockdown experienced higher psychological distress than those who did not (adjusted odds ratio [aOR] = 2.52, 95% CI, 1.02-6.48). Women experienced significantly higher SMI severity (Brief Psychiatric Rating Scale scores [x̄.

± SD] for women =56.7 ±24.4 vs men = 48.5± 19.1; [P= .039]) and higher odds of depression (OR = 2.74, 95% CI, 1.22-6.13) during the pandemic than men. Furthermore, adults with SMI with high social support experienced higher psychological distress than those with low social support (aOR = 4.60, 95% CI, 1.82-11.8).

Conclusions: The findings of this study emphasized the need to incorporate infectious disease responses with mental health interventions during a public health crisis.

Objective: There are few established treatments for negative symptoms in schizophrenia, which persist in many patients after positive symptoms are reduced. Oxidative stress, inflammation, and epigenetic modifications involving histone deacetylase (HDAC) have been implicated in the pathophysiology of schizophrenia. Sulforaphane has antioxidant properties and is an HDAC inhibitor. We conducted a 24-week, double-blind, placebo-controlled study, in Hunan, China, to assess the effect of high-dose sulforaphane (Nutramax extra strength sulforaphane tablets glucoraphanin content 30 mg/ tablet) on reducing negative symptoms in antipsychotic-treated patients with schizophrenia.

Methods: Participants were recruited from August 2020 to August 2022 and met DSM-5 criteria for schizophrenia. Participants were randomly assigned (2:1) to receive antipsychotics plus sulforaphane (1,700 mg Avmacol Extra Strength sulforaphane daily) or antipsychotics plus placebo for 24 weeks. Fifty-three patients treated with sulforaphane and 24 patients treated with placebo who had at least 1 postintervention clinical scale evaluation were analyzed. The primary outcome measure was change in the Positive and Negative Syndrome Scale (PANSS) negative symptoms.

Results: Sulforaphane-treated patients showed a significantly greater decrease in PANSS negative symptom total score (P = .01) and PANSS negative factor score (P = .02) than placebo-treated patients, with the most prominent difference occurring at 24 weeks (P ≤ .001) with a large effect size at this time point (d = 0.8). Sulforaphane's effect on decreasing negative symptoms was not mediated by changes in scores of depression or cognitive factors on the PANSS.

Conclusions: The results of this study suggest that add-on high-dose sulforaphane may reduce negative symptoms in patients with schizophrenia. The clinical significance of this reduction in negative symptoms needs further evaluation.

Trial Registration: ClinicalTrials.gov identifier: NCT04521868.

Objective: To provide proof-of-concept (PoC), dose-range finding, and safety data for BI 1358894, a TRPC4/5 ion channel inhibitor, in patients with borderline personality disorder (BPD).

Methods: This was a phase 2, multinational, randomized, double-blind, placebo controlled trial. Patients were randomized to oral placebo or BI 1358894 (5 mg, 25 mg, 75 mg, or 125 mg) once daily in a 2.5:1:1:1:2 ratio for 12 weeks. The primary end point was change from baseline in the Zanarini Rating Scale for BPD (ZAN BPD) total score at Week 10. Secondary end points included ≥30% ZAN-BPD reduction response from baseline at Week 10, change from baseline at Week 10 in the Difficulties in Emotion Regulation Scale-16 item total, State-Trait Anxiety Inventory-State Anxiety total, Patient Health Questionnaire-9 total, Clinical Global Impressions-Severity, and Patient Global Impression-Severity scores.

Results: Of 655 enrolled patients, 390 were randomized and 323 (82.8%) completed the trial. For primary and secondary end points, no differences were observed between treatment and placebo; therefore, PoC was not established. The proportion of patients with adverse events (AEs, BI 1358894 overall vs placebo: 77.9% vs 75.0%) and serious AEs (SAEs; 10.3% vs 8.6%) was comparable between treatments. The proportion of patients with an SAE of suicidal ideation was 4.2% (BI 1358894 overall) and 6.3% (placebo).

Conclusions: Although the primary end point was not met, BI 1358894 was well tolerated with no increase in self harm or suicidality. More targeted populations, alternative outcome assessments, and additional measures to minimize placebo effects should be considered for future trials.

Trial Registration: ClinicalTrials.gov identifier: NCT04566601.

Objective: The US Department of Veterans Affairs (VA) and Department of Defense (DOD) Work Group revised the 2013 VA/DOD Clinical Practice Guideline (CPG) for the Management of Bipolar Disorder (BD). This paper reviews the 2023 CPG and its development process, including how recommendations were made for evidence-based treatment in BD.

Methods: Subject experts and key stakeholders developed 20 key questions and reviewed the published literature after a systematic search using the PICOTS (population, intervention, comparator, outcomes, timing of outcomes measurement, and setting) method. The evidence was then evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. Recommendations were based on quality and strength of evidence and informed by other factors, including feasibility, patient perspectives, and the unique needs of people with BD. Peer review by an external group of experts then resulted in completion of the CPG.

Recommendations: While the scope of the CPG is broad, this synopsis focuses on clinically relevant recommendations related to the identification and management of BD, including the acute and maintenance phases of illness.

Objective: Psychiatric inpatients represent an acutely vulnerable population with high rates of suicidality (ie, suicidal ideation, attempts, and completed suicide). This systematic review aimed to evaluate treatments for suicidality delivered within inpatient settings.

Data Sources: MEDLINE, Embase, APA PsycInfo, CINAHL, and The Cochrane Library were systematically searched using 3 concepts: suicidality, inpatient population/setting, and treatment/ interventions. Searches were limited to years 2001-2024, with no language restrictions.

Study Selection: Of 19,921 articles identified, 11,519 were screened, and 179 underwent full-text review. We included clinical trials on pharmacologic and nonpharmacologic interventions for suicidality in psychiatric inpatients aged 18-65 with moderate to high levels of suicidality that measured changes in suicidality.

Data Extraction and Synthesis: Studies were organized into tables by study design, treatments, participants, suicide measure, outcomes, and key findings. Due to heterogeneity, a meta-analysis was not conducted; instead, a narrative synthesis was used for qualitative analysis.

Results: Forty-nine studies were included. Of 14 pharmacologic trials, intravenous ketamine showed most consistent rapid reduction in suicidality. Thirty-five nonpharmacologic trials, covering a broad spectrum of treatments including chronotherapy, neurostimulations, and psychotherapies, were reviewed. The results were mixed, with some interventions showing potential in reducing suicidality, particularly in the mood, personality, and trauma-related disorders. Many studies had methodological concerns including nonrandomized designs, lack of control arms, and retrospective assessments.

Conclusion: A range of interventions for treating suicidality in inpatient settings have been evaluated, with mixed results. The current review underscores the need for larger, well-designed trials to assess the effectiveness of these treatments in inpatient settings.