Effects of Intranasal (S)-Ketamine on Veterans With Co-Morbid Treatment-Resistant Depression and PTSD

Objective: Ketamine is a glutamatergic drug with potent and rapid acting effects for the treatment of depression. Little is known about the effectiveness of intranasal (S)-ketamine for treating patients with comorbid depression and PTSD. Methods: We retrospectively analyzed clinical outcomes in 35 patients with both depression and PTSD referred for (S)-ketamine treatments at the VA San Diego Neuromodulation Clinic between Jan 2020 to March 2021. Outcomes were calculated across the first 8 treatments (4 weeks, induction phase) using a repeated measures ANOVA to measure change in symptoms over treatments. In a smaller sub-group (n=19) we analyzed whether (S)-ketamine continued to show effects during the maintenance period (after 4 weeks. Sub-group analyses based on antidepressant response and general linear models were also performed to identify predictors of treatment response. Results: During the induction phase of treatment there was an absolute reduction of 4.6 +/- 0.9 on the patient health questionnaire-9 (PHQ-9) rating scale for depression, from 19.6 +/- 0.8 at treatment 1 to 14.9 +/- 0.9 at treatment 8 (week 4) (F(7,238)=6, p 50%) at treatment 8. There was an absolute reduction of 12.1 +/- 2.5 on the patient checklist 5 (PCL5) rating scale for PTSD, from 54.4 +/- 2 at treatment 1 down to 42.3 +/- 2.5 at treatment 8 (F(7,238)=10.8, p 30%) for PTSD at this time-point. After transitioning to maintenance treatments, depression and PTSD symptoms remained stable or improved.   Conclusions: Our results show that (S)-ketamine can improve both depression and PTSD symptoms in Veterans with dual-diagnoses. The effects of (S)-ketamine on PTSD were temporally and individually distinct from those on depression, suggesting potentially different modes of action on the two disorders. This work warrants further research in studying intranasal (S)-ketamine for PTSD. Funding Information: This work was supported by awards from the Department of Veterans Affairs, Veterans Health Administration (Career Development Award: 7IK2BX003308 to D.S.R.), and funding from the Center of Excellence for Stress and Mental Health (CESAMH) at the San Diego VA Medical Center, as well as from the National Institute of Mental Health (K23 MH119375-01 to E.E.L.) Declaration of Interests: None of the authors have any competing interests to declare, financial or otherwise. Ethics Approval Statement: This study was approved as an IRB-exemption by the VA San Diego Medical Center IRB committee.