Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.

BACKGROUND: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. AIMS: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. METHOD: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. RESULTS: The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h. CONCLUSIONS: Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

The course of symptoms over time in people with posttraumatic stress disorder.

OBJECTIVE: There is inadequate evidence regarding the symptom profile of people who have posttraumatic stress disorder (PTSD) over time. The goal of this study was to determine the consistency of symptoms in people with PTSD over successive assessments. METHOD: The sample comprised military personnel who participated in the Army Study to Assess Risk and Resilience in Servicemembers. Participants completed the PTSD Checklist, and this sample included those who completed two assessments. RESULTS: There were 1,164 participants with two consecutive PTSD diagnoses. Only 212 (18.2%) of participants reported the same number of symptoms over both timepoints. Intrusive memories, distress to reminders, avoidance, detachment, and sleep problems were among the most reported symptoms at the second assessment not reported initially. CONCLUSIONS: The observed pattern of findings indicate that although PTSD diagnoses often remain consistent over time, the symptoms that comprise this diagnosis can fluctuate. Clinicians should be sensitive to the changing symptoms that PTSD patients can display over time. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Dimensionality of the Swahili version of the General Health Questionnaire (GHQ-12) in a Kenyan population: A confirmatory factor analysis.

The current study evaluated the Kiswahili version of General Health Questionnaire (GHQ-12) in a Kenyan context comprising of women exposed to gender-based violence. Participants were randomly drawn from community sampling using household screening methods in peri-urban areas in Nairobi. A total of 1,394 participants with varying levels of literacy (years of education: mean [M] = 9.42; standard deviation [SD] = 3.73) and aged between 18 and 89 years were recruited for the study. The observed factor structure of the GHQ-12 was evaluated using six most tested models querying the dimensionality of the instrument insofar as the impacts of positive and negative wording effects in driving multidimensionality. Results from the confirmatory factor analysis supported a bifactor model, consisting of a general distress factor and two separate factors representing common variance due to the positive and negative wording of items. Overall, the findings support the use of the Kiswahili version of the GHQ-12 as a unidimensional construct with method-specific variance owing to wording effects. Importantly, GHQ-12 responses from a sample of Kenyan women with relatively low levels of literacy are congruent with the factor structure observed in other cross-cultural settings in low- and-middle-income countries.

Cognitive outcomes from the randomised, active-controlled Ketamine for Adult Depression Study (KADS).

BACKGROUND: Due to its rapid antidepressant effect, ketamine has recently been clinically translated for people with treatment-resistant depression. However, its cognitive profile remains unclear, particularly with repeated and higher doses. In the present study, we report the cognitive results from a recent large multicentre randomised controlled trial, the Ketamine for Adult Depression Study (KADS). METHODS: In this randomised, double-blind, active-controlled, parallel group, multicentre phase 3 trial study we investigated potential cognitive changes following repeated treatment of subcutaneous racemic ketamine compared to an active comparator, midazolam, over 4 weeks, which involved two cohorts; Cohort 1 involved a fixed dose treatment protocol (0.5 mg/kg ketamine), Cohort 2 involved a dose escalation protocol (0.5-0.9 mg/kg) based on mood outcomes. Participants with treatment-resistant Major Depressive Disorder (MDD) were recruited from 7 mood disorder centres and were randomly assigned to receive ketamine (Cohort 1 n = 33; Cohort 2 n = 53) or midazolam (Cohort 1 n = 35; Cohort 2 n = 53) in a 1:1 ratio. Cognitive measurements were assessed at baseline and at the end of randomised treatment. RESULTS: Results showed that in Cohort 1, there were no differences between ketamine and midazolam in cognitive outcomes. For Cohort 2, there was similarly no difference between conditions for cognitive outcomes. LIMITATIONS: The study included two Cohorts with different dosing regimes. CONCLUSIONS: The findings support the cognitive safety of repeated fixed and escalating doses at least in the short-term in people with treatment resistant MDD.