Response to intravenous racemic ketamine after switch from intranasal (S)‐ketamine on symptoms of treatment‐resistant depression and post‐traumatic stress disorder in Veterans: A retrospective case series.

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 are no data directly comparing outcomes on depression or other comorbidities 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 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 (across 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 = 0.1) and by an average of 5.6 ± 1 after IV‐ketamine treatments (p = 0.0003) compared to pretreatment 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 = 0.03) compared to pretreatment baseline 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. [ABSTRACT FROM AUTHOR]