1. Response to Intravenous Racemic Ketamine After Switch From Intranasal (S)-ketamine on Symptoms of Treatment-Resistant Depression and PTSD in Veterans: a Retrospective Case Series
- Author
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Bentley, S., Artin, H., Mehaffey, E., Liu, F., Sojourner, K., Bismark, A., Printz, D., Lee, E.E, Martis, B., De Peralta, S., Baker, D.G., Mishra, J., and Ramanathan, D.
- Subjects
Article - Abstract
BACKGROUND. Racemic (R,S) ketamine is a glutamatergic drug with potent and rapid acting antidepressant effects. An intranasal formulation of (S)-ketamine was recently approved by the US Food and Drug Administration (FDA) to be used in individuals with treatment-resistant-depression (TRD). There is no data directly comparing outcomes on depression or other co-morbidities between these two formulations of ketamine. However, recent meta-analyses have suggested that IV racemic ketamine may be more potent than IN-(S)-ketamine. METHODS. We retrospectively analyzed clinical outcomes in 15 Veterans with comorbid treatment resistant depression (TRD) and post-traumatic-stress-disorder (PTSD) who underwent ketamine treatment at the VA San Diego Neuromodulation Clinic. All Veterans included in this analysis were given at least 6 intranasal (IN)-(S)-ketamine treatments prior to switching to treatment with IV racemic ketamine. RESULTS. Veterans receiving ketamine treatment (including both IN-(S)-ketamine and IV-(R,S)-ketamine), showed significant reductions in both the Patient Health Questionnaire-9 (PHQ-9), a self-report scale measuring depression symptoms (rm ANOVA F(14,42) = 12.6, p < 0.0001) and in the PTSD- Checklist for DSM-5 (PCL-5), a self-report scale measuring PSTD symptoms (rm ANOVA F(13,39) = 5.9, p = 0.006). Post-hoc testing revealed that PHQ-9 scores were reduced by an average of 2.4 +/− 1.2 compared to baseline after (S)-ketamine treatments (p=0.18) and by an average of 5.6 +/−1 after IV ketamine treatments (p=.0003) compared to pre-treatment baseline scores. PCL-5 scores were reduced by an average of 4.3 +/− 3.3 after IN (S)-ketamine treatments (p = 0.6) and 11.8 +/− 3.5 after IV ketamine treatments (p = 0.02) compared to pre-treatment base-line scores. CONCLUSIONS. This work suggests that off-label IV (R,S)-ketamine could be considered a reasonable next step in patients who do not respond adequately to the FDA-approved IN (S)-ketamine. Further double-blinded, randomized-controlled-trials are warranted to assess whether IV racemic ketamine is more effective than IN-(S)-ketamine.
- Published
- 2022