Examining the impact of comorbid posttraumatic stress disorder on ketamine's real-world effectiveness in treatment-resistant depression

Dec 6, 2024European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

How PTSD may affect ketamine's effectiveness in hard-to-treat depression

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Abstract

A significant reduction in depression symptoms was observed in 134 treatment-resistant depression patients receiving four ketamine infusions.

Ketamine infusions (0.5-0.75 mg/kg) were effective in reducing depression symptoms, as measured by the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16).
No difference in antidepressant effectiveness was found between patients with and without comorbid PTSD.
Significant improvements in PTSD symptoms were recorded, with moderate to large effect sizes across all symptom clusters measured by the PTSD Checklist for DSM-5 (PCL-5).
Overall, ketamine demonstrated effectiveness in alleviating symptoms of both depression and PTSD in treatment-resistant patients.

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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.

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Examining the impact of comorbid posttraumatic stress disorder on ketamine's real-world effectiveness in treatment-resistant depression

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