Ketamine Dose and Duration Effects in Internalizing Disorders

The dose-response profile of racemic ketamine in internalizing disorders is poorly characterized. This was a secondary analysis of outcome responses in patients with treatment-resistant depression, post-traumatic stress disorder, generalized and/or social anxiety, or obsessive-compulsive disorder. For each disorder, they received single intramuscular doses of racemic ketamine (0.5 and 1.0 mg/kg) and a psychoactive control, using a three-way within-subject double-blind active-controlled cross-over design. Intramuscular racemic ketamine doses of 0.5 and 1.0 mg/kg produced robust effects on diagnosis-appropriate outcome scales for all these internalizing disorders, compared with psychoactive controls. These effects were most obvious at 24 h after dosing and noticeably smaller at 168 h. The magnitude of change after 1 mg/kg did not differ significantly from 0.5 mg/kg at either time point, and did not differ significantly between the internalizing disorders at 24 h. When combined with other ketamine dose-response data, we propose that ketamine may have a narrow inverted-U dose-response profile (peaking in the regions of 0.5-1.0 mg/kg) in patients with internalizing disorders.