Ascending-Dose Subcutaneous Ketamine for Treatment-Refractory Anxiety Disorders: Dose-Finding Study (Glue 2017, University of Otago, ANZCTR)
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).
Study Arms & Interventions
Ketamine 0.25mg/kg
experimentalSubcutaneous administration of 0.25 mg/kg ketamine
Interventions
- Ketamine0.25 mg/kgvia subcutaneous• single dose• 1 doses total
Administered at 1-week intervals in an ascending dose design
Ketamine 0.5mg/kg
experimentalSubcutaneous administration of 0.5 mg/kg ketamine
Interventions
- Ketamine0.5 mg/kgvia subcutaneous• single dose• 1 doses total
Administered at 1-week intervals in an ascending dose design
Ketamine 1mg/kg
experimentalSubcutaneous administration of 1 mg/kg ketamine
Interventions
- Ketamine1 mg/kgvia subcutaneous• single dose• 1 doses total
Administered at 1-week intervals in an ascending dose design
Midazolam 0.01mg/kg
active comparatorSubcutaneous administration of 0.01 mg/kg midazolam as an active control
Interventions
- Placebo0.01 mg/kgvia subcutaneous• single dose• 1 doses total
Counterbalanced in dosing position across patients
Primary Results(2 publications)
Participants
FQ
Score at Timepoint
Adverse Events (from all publications)
| Arm / Group | n | Any TEAE | Severe | Serious | Discont. |
|---|---|---|---|---|---|
| Ketamine 0.25mg/kgexperimental | 12 | 12(100.0%) | — | 0(0.0%) | 0(0.0%) |
| Ketamine 0.5mg/kgexperimental | 12 | 12(100.0%) | — | 0(0.0%) | 0(0.0%) |
| Ketamine 1mg/kgexperimental | 12 | 12(100.0%) | 2(16.7%) | 0(0.0%) | 0(0.0%) |
| Midazolam 0.01mg/kgactive_comparator | — | — | — | — | — |
| Ketamine 0.25mg/kgexperimental | 12 | — | — | — | 1(8.3%) |
| Ketamine 0.5mg/kgexperimental | 12 | — | — | — | — |
| Ketamine 1mg/kgexperimental | 12 | — | — | — | — |
| Midazolam 0.01mg/kgactive_comparator | 12 | — | — | — | — |
* This was a within-subject study where all 12 participants received this dose. 'All subjects reported dissociative symptoms' is a general statement for ketamine treatment across doses. No specific severe TEAEs were reported for this dose level.
* This was a within-subject study where all 12 participants received this dose. 'All subjects reported dissociative symptoms' is a general statement for ketamine treatment across doses. Two subjects rated experiences as 'very intense, feeling out of control' after the 1 mg/kg dose, which is considered severe.
* No Midazolam arm was described in the study. The study was an open-label, ascending single-dose study of ketamine only.
* One participant discontinued intervention due to poor tolerability. The study used a crossover design where 12 patients received all doses.
* Summary TEAE counts not explicitly provided per dose in text.