Depression with comorbid posttraumatic stress disorder (PTSD) is associated with more severe symptoms and a reduced response to traditional treatments. Although ketamine shows promise as a rapid-acting antidepressant for treatment-resistant depression (TRD), its effectiveness in patients with comorbid PTSD remains underexplored. Therefore, we conducted a retrospective analysis of 134 patients from the Canadian Rapid Treatment Center of Excellence to compare the effectiveness of four ketamine infusions (0.5-0.75 mg/kg) in reducing symptoms of depression and PTSD in TRD patients with and without comorbid PTSD. A repeated-measures linear mixed model was used to evaluate the impact of comorbid PTSD on ketamine's antidepressant effectiveness, measured by the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Paired samples t-tests were used to assess changes in PTSD symptoms, measured by the PTSD Checklist for DSM-5 (PCL-5). We found a significant main effect of time on QIDS-SR16 scores, F(4, 209.32) = 36.67, p < 0.001, but no significant group-by-time interaction (p = 0.895), suggesting that comorbid PTSD did not impact the antidepressant effectiveness of ketamine. Significant improvements in PTSD symptoms were observed in overall PCL-5 scores, t(66) = 6.66, p < 0.001, and across all PCL-5 symptom clusters with moderate to large effect sizes. In a real-world sample of TRD patients, ketamine was effective in reducing symptoms of depression and PTSD, regardless of PTSD comorbidity. These findings highlight ketamine's potential as a novel intervention for a patient population that is frequently non-responders to conventional treatments. Future randomized controlled trials should explore mediating factors of improvement and long-term effects.
