Prospective within-subject ascending-dose study (J Psychopharmacol 2017; Glue P, Medlicott NJ, Harland S, Neehoff S, Anderson-Fahey B, Le Nedelec M, Gray A, McNaughton N; University of Otago, Dunedin, New Zealand; DOI 10.1177/0269881117705089). Registered with the Australian New Zealand Clinical Trial Registry (ANZCTR); number not reported in extracted methods text, PubMed DataBankList, or CrossRef. Participants: 12 adults (4 male, 8 female; mean age 31 yr) with treatment-refractory DSM-IV GAD and/or SAD (HAM-A ≥20 and/or LSAS ≥60; failed ≥2 antidepressant courses; MADRS <20). No control arm (within-subject design). Intervention: subcutaneous ketamine at three ascending dose levels (0.25, 0.5, 1.0 mg/kg) plus an active control (midazolam 0.01 mg/kg) administered once weekly; doses given in fixed ascending order with midazolam randomly inserted. Participants continued stable ongoing medications. Primary outcomes: HAM-A and Fear Questionnaire (FQ). Companion papers: anxiety symptoms (Glue P et al. J Psychopharmacol 2017) and EEG (Glue P et al. Int J Neuropsychopharmacol 2018, PMID 29718262).
Subcutaneous administration of 0.25 mg/kg ketamine
Administered at 1-week intervals in an ascending dose design
Subcutaneous administration of 0.5 mg/kg ketamine
Administered at 1-week intervals in an ascending dose design
Subcutaneous administration of 1 mg/kg ketamine
Administered at 1-week intervals in an ascending dose design
Subcutaneous administration of 0.01 mg/kg midazolam as an active control
Counterbalanced in dosing position across patients
This randomised, double-blind, active placebo-controlled study (n=12) investigated the effects of 3 ascending ketamine dose levels (17.5/35/70mg/70kg) and midazolam (0.7mg/70kg) on electrophysiological brain activity in patients with anxiety. While ketamine increased high-frequency brain rhythms and decreased low-frequency rhythms in a dose-dependent manner, only decreases within the frontal theta frequency band were related to improvements in anxiety.