Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial

Abstract

This study tested the efficacy of repeated intravenous ketamine doses to reduce symptoms of posttraumatic stress disorder (PTSD). Veterans and service members with PTSD ( n = 158) who failed previous antidepressant treatment were randomized to 8 infusions administered twice weekly of intravenous placebo ( n = 54), low dose (0.2 mg/kg; n = 53) or standard dose (0.5 mg/kg; n = 51) ketamine. Participants were assessed at baseline, during treatment, and for 4 weeks after their last infusion. Primary analyses used mixed effects models. The primary outcome measure was the self-report PTSD Checklist for DSM-5 (PCL-5), and secondary outcome measures were the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery Åsberg Depression Rating Scale (MADRS). There were no significant group-by-time interactions for PTSD symptoms measured by the PCL-5 or CAPS-5. The standard ketamine dose ameliorated depression measured by the MADRS significantly more than placebo. Ketamine produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 h and were less pronounced with repeated administration. There was no evidence of differential treatment discontinuation by ketamine dose, consistent with good tolerability. This clinical trial failed to find a significant dose-related effect of ketamine on PTSD symptoms. Secondary analyses suggested that the standard dose exerted rapid antidepressant effects. Further studies are needed to determine the role of ketamine in PTSD treatment. ClinicalTrials.gov identifier: NCT02655692.

The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence

“…Ketamine-induced dissociative and psychotomimetic symptoms were transient, resolving completely within 1–2 h on average. However, findings regarding efficacy are still mixed, with the largest RCT 87 failing to identify significant dose-related effects of ketamine on PTSD. While this was specific to veterans and military personnel, more robust data are patently needed.…”

“…Given that benzodiazepines have potential to worsen PTSD outcomes, 86 Abdallah et al . 87 compared an inactive placebo to active comparators in a double-blind, three-arm RCT. Here, investigators tested the efficacy of repeat ketamine in veterans and active-duty military with refractory PTSD.…”

Acute Effects of Intravenous Sub-Anesthetic Doses of Ketamine and Intranasal Inhaled Esketamine on Suicidal Ideation: A Systematic Review and Meta-Analysis

“…However, ketamine had no statistically significant effect after 24 hours, suggesting that the effect may be transient, and other authors have reported similar results. [36][37][38] But there are also studies showing that ketamine can rapidly reduce SI in depressed patients within 1 day and 1 week. 39,40 The antidepressant effect of ketamine was reported to start after 2 hours and last for 1 week.…”

Registered clinical trials investigating ketamine and esketamine for treatment-resistant depression: A systematic review

“…Descriptive analyses further revealed important gaps in demographic and clinical characteristics. Patients with TRD have increased rates of psychiatric comorbidity, the most common being anxiety, substance use, post-traumatic stress disorder (PTSD), personality disorders, and non-organic psychosis (Abdallah et al, 2019(Abdallah et al, , 2022Huang et al, 2020). In this review, only one trial clearly examined ketamine for TRD with a psychiatric comorbidity, PTSD (Albott et al, 2018).…”