Ketamine Therapy Shows Promise for in Treatment-Resistant Patients with Comorbid PTSD and MDD

Recent setbacks in PTSD treatment development, including the FDA's decision to delay approval for MDMA-assisted therapy, underscore the urgent need for effective treatments for the more than 13 million Americans suffering from PTSD. While traditional treatments like SSRIs help some patients, only 20-30% achieve complete remission, often leading to complex medication regimens in clinical practice.New research examining ketamine intravenous therapy (KIT) in real-world settings may offer hope for treatment-resistant PTSD patients, particularly those with comorbid depression.


The study, presented by Dr. L. Alison McInnes and Dr Robert Berman (author of the first ever KIT trial for depression, leverages one of the largest real-world databases of KIT treatment outcomes.

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Methods
‍In this retrospective analysis, researchers examined data from Osmind's electronic health record database of over 8,000 PTSD patients receiving KIT in community practice settings. The analysis focused on 1,306 patients who completed both baseline and post-treatment assessments using the PTSD Checklist for DSM-5 (PCL-5), which measures symptom severity on a scale of 0-80, with scores above 31-33 indicating need for treatment.The patient population reflected typical community psychiatric practice: predominantly female (66%) and Caucasian (94%), with a mean age of 42.3 years. Most patients presented with multiple psychiatric comorbidities, including Major Depressive Disorder (90%), Generalized Anxiety Disorder (72%), ADHD (33%), and panic disorder (19%).

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Results
‍The findings revealed significant symptom improvement during the induction phase of KIT administration:‍• Patients showed an average decrease of 18.6 points in PCL-5 scores, dropping from a baseline of approximately 47 to 27 after four infusions• Response rates (defined as ≥30% reduction from baseline) increased progressively:◦ 27% after first infusion◦ 65% after fourth infusion◦ 73% after sixth infusion◦ Most patients (82%) completed the four-infusion induction phase within 28 days◦ Mean dose at final infusion during induction phase was 1.02 mg/kg (SD=0.39)

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Clinical Implications

‍These results suggest that KIT may offer a viable treatment option for PTSD patients, particularly those who haven't responded adequately to traditional treatments. The high proportion of patients with comorbid MDD in this study is especially noteworthy, as recent research suggests PTSD+MDD may represent a distinct trauma-related phenotype with greater impairment and suicide risk.‍

‍While promising, several important limitations should be considered:‍
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‍• Complete outcome data was available for only 16.5% of the total 8,142 PTSD patients receiving KIT‍ (50% of these patients did receive the PHQ9 pre and post however showing that treatment adherence was comparable to McInnes et al. 2022 & Hietamies et al. 2023 for depression)
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• The study population was largely Caucasian females in their forties, which may limit generalizability to other demographic groups• The PCL-5's one-month look-back period may not be ideally suited for rapid-acting agents like ketamine
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• Most patients had multiple comorbidities, suggesting findings may be most applicable to complex cases‍‍

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Future Directions

‍As the field awaits further developments in psychedelic medicine, these findings suggest KIT could provide an important treatment option for PTSD patients, especially those with comorbid depression. Further research is needed to optimize treatment protocols and identify patients most likely to benefit from this approach.‍

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