Clinical TrialTreatment-Resistant Depression (TRD)KetaminePlaceboCompleted

Effectiveness of ketamine therapy among patients with treatment-resistant depression: a double-blind, randomised, controlled trial

This double-blind, randomised, controlled trial (n=183), known as the Ketamine for Adult Depression Study (KADS), explored the effectiveness of ketamine therapy in treating patients with treatment-resistant depression (TRD).

Target Enrollment
183 participants
Study Type
Phase III interventional
Design
Randomized, double Blind

Detailed Description

Randomised, double-blind RCT phase: subcutaneous ketamine (100 mg/mL) given twice weekly for 4 weeks; participants screened 1 month after RCT for eligibility to enter a 4-week open-label extension after a 1-month break.

Dosing is weight-based by volume (0.22–0.53 mL starting volumes depending on body weight) with the possibility of dose increases up to 0.91 mL; adherence ensured by staff-administered injections. Primary outcome: remission at end of RCT phase (MADRS <10); MADRS change also assessed.

Study Protocol

Preparation

sessions

Dosing

8 sessions

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Subcutaneous ketamine administered twice weekly for 4 weeks (RCT phase) with optional 4-week open-label extension after 1-month break.

Interventions

  • Ketamine0.22 - 0.91 ml
    via Other• twice weekly• 8 doses total

    Concentration 100 mg/mL; starting volume based on body weight (see table); subcutaneous injection. Starting volumes: 41-45 kg 0.22 mL; 46-50 kg 0.24 mL; 51-55 kg 0.27 mL; 56-60 kg 0.29 mL; 61-70 kg 0.33 mL; 71-80 kg 0.38 mL; 81-90 kg 0.43 mL; 91-100 kg 0.48 mL; >100 kg 0.53 mL. Dose may be increased depending on tolerability; maximum 0.91 mL.

Active control

active comparator

Active control drug administered during RCT (unspecified in source text).

Interventions

  • Placebo

    Specified only as an active control in source text; agent and dosing not provided.

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Criteria assessed by the research team include:
  • Major Depressive Disorder (MDD) for at least 3 months.
  • An inadequate response to at least 2 adequate antidepressant courses; stable dose of antidepressant medications at least 4 weeks prior to trial entry.
  • Montgomery Åsberg Depression Rating Scale (MADRS) score of at least 20.

Exclusion Criteria

  • Criteria assessed by the research team to determine suitability include:
  • Psychotic disorder.
  • Bipolar disorder.
  • Medical and neurologic conditions.
  • Psychiatric disorders other than MDD.
  • Planned major changes to psychotropic medication.
  • Planned or probable use of ECT.
  • Risk of suicide.
  • Substance use, abuse, dependence.
  • Recent or planned ketamine treatment.
  • Medical conditions in which use of ketamine or sedating medications may pose a significant health risk.
  • Women of childbearing potential not taking reliable contraception.
  • Inability to complete the trial.

Primary Results(3 publications)

Participants

N = 86Mean age: 45.9–46.2 across armsC. et al. 2023 →
N = 174T. et al. 2025 →
N = 86Mean age: 45–46 across armsL. et al. 2025 →

MADRS

Score at Timepoint

Active control—Day 28·C. et al. 2023 →
Ketamine—Day 28·C. et al. 2023 →
Active control—Day 28·C. et al. 2023 →
Ketamine—Day 28·C. et al. 2023 →

HAM-A

Score at Timepoint

Active control—Day 28·T. et al. 2025 →
Ketamine—Day 28·T. et al. 2025 →

AQoL-8D

Score at Timepoint

Active control—Day 28·L. et al. 2025 →
Ketamine—Day 28·L. et al. 2025 →

QALYs

Score at Timepoint

Active control—Day 28·L. et al. 2025 →
Ketamine—Day 28·L. et al. 2025 →
Active control—Day 56·L. et al. 2025 →
Ketamine—Day 56·L. et al. 2025 →

Adverse Events (from all publications)

Arm / GroupnAny TEAESevereSeriousDiscont.
Ketamineexperimental68——0(0.0%)2(2.9%)
Active controlactive_comparator106——3(2.8%)—
Ketamineexperimental174————
Active controlactive_comparator174————
Ketamineexperimental53————
Active controlactive_comparator53————

* Cohort 1 (fixed-dose). 2 participants discontinued due to non-serious adverse events (skin rash, increased anxiety, headache, or increased depression). Serious adverse events were reported as none in the ketamine group for cohort 1.

* Cohort 2 (flexible-dose). Midazolam group (active control) had 3 serious adverse events (suicide attempt, increased suicidal ideation, and wrist injury). Ketamine group had 2 serious adverse events (major dissociative episode and auditory hallucination).

* The paper reports that 174 participants received at least one dose of the study drug. Specific TEAE counts are not provided in the visible text or tables.

* The paper mentions 'few drug-related adverse events' in the introduction, but does not provide summary counts for TEAEs in the provided text/tables. Data focuses on economic evaluation.

Study Details

Locations

Unknown facility — Australia

Related Publications

Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial

Published
Authors
Loo, C., Glozier, N., Barton, D., Baune, B. T., Mills, N. T., Fitzgerald, P., Glue, P., Sarma, S., Galvez-Ortiz, V., Hadzi-Pavlovic, D., Alonzo, A., Dong, V., Martin, D., Nikolin, S., Mitchell, P. B., Berk, M., Carter, G., Hackett, M., Leyden, J., Hood, S., Somogyi, A. A., Lapidus, K., Stratton, E., Gainsford, K., Garg, D., Thornton, N. L. R., Fourrier, C., Richardson, K., Rozakis, D., Scaria, A., Mihalopoulos, C., Chatterton, M. L., McDonald, W. M., Boyce, P., Holtzheimer, P. E., Kozel, F. A., Riva-Posse, P., Rodgers, A.

Effect of ketamine on anxiety: findings from the Ketamine for Adult Depression Study

Published
Authors
Mills, N. T., Nikolin, S., Glozier, N., Barton, D., Baune, B. T., Fitzgerald, P. B., Glue, P., Sarma, S., Rodgers, A., Hadzi-Pavlovic, D., Alonzo, A., Dong, V., Martin, D., Mitchell, P. B., Berk, M., Carter, G., Hackett, L., Somogyi, A. A., Mihalopoulos, C., Chatterton, M. L., Hood, S., Loo, C. K.

Economic evaluation of subcutaneous ketamine injections for treatment resistant depression: A randomised, double-blind, active-controlled trial - The KADS study

Published
Authors
Chatterton, M. L., Perez, J. K., Thai, T., Faller, J., Loo, C. K., Glozier, N., Barton, D., Baune, B. T., Mills, N. T., Fitzgerald, P. B., Glue, P., Sarma, S., Hadzi-Pavlovic, D., Dong, V., Martin, D., Mitchell, P. B., Berk, M., Carter, G., Hackett, M., Hood, S., Somogyi, A. A., Rodgers, A., Mihalopoulos, C.

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