Journal of Clinical Psychiatry最新文献

Ketamine, introduced as an anesthetic drug, is now used for many indications beyond anesthesia; it is also increasingly a drug of abuse. Long-term recreational use and abuse of ketamine are associated with urological risks. This article discusses ketamine-associated uropathy from the perspective of prevalence, clinical features, mechanisms, and strategies for risk reduction in patients who require long term maintenance therapy with the drug for psychiatric indications. A systematic review and meta-analysis of 37 studies of uropathy in recreational (ab)users obtained prevalences of 44% to 77% for lower urinary tract symptoms and 8% to 30% for upper urinary tract disease; for reasons explained, these findings are potentially misleading and cannot be extrapolated to therapeutic contexts. More recent studies, using different methods of case ascertainment, present lower risks (2% to 27%). A systematic review of 27 studies of ketamine used to treat psychiatric disorders, mainly depression, found urological symptoms in 0% to 24% of patients; however, in 14 randomized controlled trials, urological symptom prevalences differed little between ketamine and comparison arms. The review presented no convincing evidence of ketamine-associated uropathy arising in therapeutic contexts. The literature on ketamine-associated uropathy is critically examined; reasons for false positive uropathy findings are considered. Ketamine pharmacokinetics are described to assist the understanding of how ketamine and its metabolites may predispose to uropathy. Mechanisms of uropathy, arising from exposure to ketamine and its metabolites in urine (rather than in circulation), are summarized. A reasonable conclusion is that higher doses of ketamine, more frequent dosing with ketamine, longer duration of treatment with ketamine, and oral administration of ketamine are all potential risk factors for ketamine-associated uropathy during maintenance therapy. High hydration and frequent voiding of urine on treatment days can reduce exposure of the bladder to ketamine and its metabolites, reducing urological risks. Fortnightly or monthly urine testing is also advisable.

Objective: To compare the results of a proprietary online assessment of adult attention-deficit/hyperactivity disorder (ADHD) with the current standard of care, a clinical interview, among a real-world population of adults seeking online ADHD assessment.

Methods: Participants recruited from a population of adults seeking online ADHD assessment completed a virtual clinical interview followed by the online self-report assessment between July and November 2024. Agreement was calculated using a 2×2 matrix, and disagreement was further examined: first, a licensed clinician reviewed both assessments and rendered a "full data" diagnosis using all available results, and then, factors associated with disagreement (eg, psychiatric comorbidities, ADHD presentation) were explored.

Results: The sample (N = 345) was predominantly female, with an approximate age of 35 years. The most common ADHD presentations were combined and inattentive. The agreement between assessments was 78% (positive predictive value: 94.9%, negative predictive value: 15.1%, sensitivity: 80.6%, specificity: 44.0%, and κ: 0.13). Over 80% of cases in which there was disagreement between the assessments were found to have ADHD on clinical interview, whereas the initial online assessment did not confirm a diagnosis of ADHD and recommended further assessment.

Conclusions: This is the first study to validate an online asynchronous ADHD assessment relative to the current standard of care among individuals seeking online behavioral health care. The online assessment correctly identified over 80% of ADHD-positive cases. Compared with the clinical interview, the online assessment was more conservative in rendering ADHD-positive diagnoses, allaying possible concerns about overdiagnosis. Due to the high prevalence of ADHD in the study sample, these results are not yet generalized to a broader clinical setting.

Objective: To assess proof-of-concept (PoC) for efficacy, tolerability, and safety of TRPC4/5 inhibitor BI 1358894 vs placebo in patients with major depressive disorder (MDD) with inadequate response to ongoing antidepressants.

Methods: In this phase 2, multicenter, randomized, double-blind, dose-finding trial (December 2020-February 2024), patients with MDD (per DSM-5) and current depressive episode of ≥8 weeks and ≤24 months were randomized (3.5:1:1:1:2:2) to receive placebo or BI 1358894 (5 mg, 25 mg, 75 mg, or 125 mg) or quetiapine 150-300 mg orally, once daily for 6 weeks. Primary end point was change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6. Secondary end points included ≥50% reduction from baseline in MADRS total score at Week 6, change from baseline in State-Trait Anxiety Inventory scores, Clinical Global Impression Severity Scale score, and Symptoms of Major Depressive Disorder Scale total score at Week 6.

Results: Of 940 enrolled patients, 389 were randomized, and 361 (93.0%) completed the trial. No differences were observed between BI 1358894 treatment groups and placebo for primary and secondary end points. Adverse events were slightly more frequent in the BI 1358894-total group (66.7%) vs placebo (53.9%). No worsening of Columbia-Suicide Severity Rating Scale was observed for most patients; serious adverse events of suicidal ideation were reported for 4.7% (placebo), 5.1% (BI 1358894 75 mg group), and 1.4% (quetiapine) of patients.

Conclusion: Although this was a negative trial in MDD with PoC not established, BI 1358894 was well tolerated with no increase in self-harm or suicidality.

Trial Registration: ClinicalTrials.gov identifier: NCT04521478.

Objective: Electroconvulsive therapy (ECT) has potent antidepressant effects yet can lead to neurocognitive side effects. Ketamine is a rapid-acting antidepressant, which may be an alternative to ECT. Few have directly compared the cognitive effects of ECT and ketamine treatment.

Methods: We compared cognitive effects of intravenous ketamine and ECT in patients with treatment-resistant depression (TRD), collected through a multisite, randomized trial conducted between April 2017 and November 2022 (the ELEKT-D study). Participants received 6 IV ketamine treatments or 9 ECT sessions. Cognitive functioning was assessed through 4 validated cognitive tasks at pre- and posttreatment visits. The Squire Memory Complaint Questionnaire (SMCQ) and Global Self-Evaluation of Memory (GSE-My) were used to measure changes in memory functioning. Responders (those who achieved ≥50% reduction in depressive symptoms) were evaluated again at 1-, 3-, and 6-month follow-up visits.

Results: In the intent-to-treat sample (N = 365), ECT recipients performed significantly worse than ketamine recipients on all cognitive tasks at end of treatment (P < .001), with no significant differences in task performance associated with response to either treatment. Among responders, we observed no significant group differences at 1-, 3-, and 6-month follow-up. Analyses of subjective memory questionnaires were mixed. SMCQ scores improved for both groups with ketamine recipients reporting greater functional gains; ketamine-treated patients reported improvements in GSE-My scores while ECT-treated patients reported a decline in GSE-My scores. Within-group analyses in the ketamine group found improvements in executive functioning and cognitive flexibility. This survived adjustments for changes in depression, suggesting partial independence of cognitive and mood effects.

Conclusions: Patients treated with ketamine demonstrated superior cognitive functioning compared with those treated with ECT following a 3-week treatment course, with no differences between treatments observed among responders in follow-up. Findings support the short-term superiority of ketamine on cognitive functioning and the long-term cognitive safety of both treatments for TRD.

Trial Registration: ClinicalTrials.gov identifier: NCT03113968.

Background: On October 7, 2023, Israel experienced a large-scale terrorist attack followed by a prolonged war, exposing civilians and military personnel to acute and sustained trauma. While prior studies have documented short-term psychological effects of mass trauma, few have included baseline assessments or addressed long-term trajectories across distinct exposure groups. In this study, we aimed to examine changes over time in both probable diagnoses and symptom severity of posttraumatic stress disorder (PTSD), depression, anxiety, and suicidal ideation (SI), while accounting for preattack symptom levels among different exposed groups.

Methods: A prospective, representative study assessed 614 Israeli participants (309 females; 50.3%) through an online survey conducted across 3 time points: prior to the attack (T1), 1 month after (T2), and 1 year later (T3). Participants were categorized into 4 mutually exclusive exposure groups based on a predefined hierarchy prioritizing the most impactful exposure: direct exposure, bereavement (loss of a close other), reserve-duty combatants, and indirect exposure. Probable diagnoses of PTSD (using the International Trauma Questionnaire), depression (Patient Health Questionnaire-2), and anxiety (Generalized Anxiety Disorder-2) were assessed along with symptom severity and SI (SI by the Columbia-Suicide Severity Rating Scale). Generalized estimating equations were used to examine main and interaction effects of exposure type and time (T2 to T3), controlling for baseline symptom levels (T1).

Results: Overall, prevalence and severity of psychiatric symptoms declined between T2 and T3. However, exposure group moderated these changes. Reserve-duty combatants exhibited the highest rates of probable diagnoses and symptoms at both time points, with minimal improvement over time. In contrast, indirectly exposed participants demonstrated significant symptom reduction. Uniquely, SI increased over time among reserve-duty participants, highlighting their vulnerability.

Conclusions: Recovery following mass trauma such as the October 7th attack is not uniform. Exposure type and initial distress levels shape distinct psychological trajectories. Findings underscore the importance of differentiated, long-term, and trauma-informed interventions-especially for bereaved and reserve-duty individuals. Integration of baseline mental health data enhances risk identification and has critical implications for both clinical care and policy planning in the context of ongoing national crises.

Introduction: Suicide is a leading cause of death globally. Although prior suicidal behavior is the strongest predictor of future attempts, clinical outcomes following a first suicide attempt (FSA) remain poorly understood. This study evaluates 5-year outcomes after an FSA, focusing on recurrence, lethality, and mortality to address gaps in understanding clinical trajectories and risk factors.

Methods: A cohort of 387 FSA patients was followed for 5 years. Sociodemographic and clinical data were collected at baseline and during follow-up. Outcomes included recurrence, lethality of subsequent attempts, and all-cause mortality. Multivariable logistic and Cox regression models were used to identify risk factors.

Results: During follow-up, 37.2% of patients experienced recurrence, with 27.8% classified as frequent reattempters (≥3 attempts). Overall, 5.7% of participants died, including 1.8% by suicide. High-lethality FSAs were observed in 17.3% of the sample and were strongly associated with alcohol use (odds ratio [OR], 2.142; 95% CI, 1.231-3.724; P=.021). Female sex was a significant risk factor for multiple reattempts (OR, 2.388; 95% CI, 1.036-5.507; P=.041). High-lethality FSAs significantly increased the risk of suicide deaths (hazard ratio [HR], 5.430; 95% CI, 1.189-24.792; P=.029), while older age was associated with a higher risk of nonsuicidal deaths (HR, 1.093; 95% CI, 1.035-1.153; P=.001).

Conclusions: Lethality, recurrence, and mortality following an FSA are influenced by distinct risk factors. Alcohol use predicted high-lethality FSAs, female sex predicted multiple reattempts, high-lethality FSAs predicted suicide deaths, and age predicted nonsuicidal deaths. Targeted interventions for these high-risk populations are needed.