Intranasal Ketamine vs Midazolam for TRD: Double-Blind Parallel Pilot RCT (Gálvez 2018, Thompson Institute / Otago)
Double-blind parallel pilot RCT suspended early for tolerability (J Psychopharmacol 2018; Gálvez V, Li A, Huggins C, Glue P, Martin D, Somogyi AA; Thompson Institute / UNSW Australia + University of Otago NZ; PMID 29542371). Target: n=10 (5/arm); suspended after n=5 enrolled due to acute adverse effects. Participants: DSM-5 unipolar MDE ≥3 months, MADRS ≥20, failed ≥2 adequate antidepressants; exclusions: non-MDD primary diagnosis, suicidal risk, substance dependence, lifetime ketamine misuse. Randomised to intranasal ketamine (100 mg as 1 mL via atomiser, ten 100-μL sprays) vs intranasal midazolam (4.5 mg) active control; 8 treatments over 4 weeks (3×/week × 2 weeks, then weekly × 2 weeks). Dosing protocol modified early (initial 2 sprays q10 min → 1 spray q5 min alternating nostrils) to manage adverse effects. Participants monitored 4h post-dose; CogState battery, mood (MADRS, HAM-A) and safety (CADSS, BPRS, BPIC-SS, LFTs) assessed. CT.gov: 0 hits; no registration number in methods.
Study Arms & Interventions
Ketamine
experimentalA 4-week course of eight intranasal ketamine treatments (100 mg per treatment, administered as 10 separate sprays).
Interventions
- Ketamine100 mgvia intranasal• three times a week for 2 weeks, then weekly for 2 weeks• 8 doses total
Each treatment consisted of 10 separate IN sprays, self-administered 5 min apart (later modified to 5 min intervals between sprays due to tolerability).
Midazolam
active comparatorA 4-week course of eight intranasal midazolam treatments (4.5 mg per treatment, administered as 10 separate sprays).
Interventions
- Placebo4.5 mgvia intranasal• three times a week for 2 weeks, then weekly for 2 weeks• 8 doses total
Each treatment consisted of 10 separate IN sprays.
Primary Results(1 publication)
Participants
Adverse Events (from all publications)
| Arm / Group | n | Any TEAE | Severe | Serious | Discont. |
|---|---|---|---|---|---|
| Ketamineexperimental | 3 | 3(100.0%) | 3(100.0%) | 0(0.0%) | 3(100.0%) |
| Midazolamactive_comparator | 2 | 1(50.0%) | — | 0(0.0%) | 2(100.0%) |
* All 3 participants experienced acute side effects described as 'moderate to severe' (e.g., light-headedness, inability to walk, metallic taste) and discontinued the study due to tolerability issues.
* One participant experienced drowsiness. Both participants discontinued the study due to the overall study suspension for tolerability issues, although the midazolam group did not experience the same level of acute tolerability problems as the ketamine group.