Table 1 Description of included studies.
Investigator(s) | Study country | Patientsa | Ketamine protocol | Control condition(s) | Study Design | Minimum ADM treatment failures required for eligibility | Excluded psychiatric diagnoses/conditions | Concurrent psych meds | Eligible Depression Measures Provided |
|---|---|---|---|---|---|---|---|---|---|
UK | MDD outpatients (n = 37) | Single infusion 0.5 mg/kg | Saline; Lanicemineb | Parallel Arm | Unspecified (no requirement) | Lifetime history of psychosis, bipolar disorder, or alcohol/substance use disorder, not right-handed, consuming more than 10 cigarettes or 8 cups of caffeinated beverages per day, positive tox screen | Unmedicated/washout period | MADRS | |
Feder #1 [46] | US | PTSD outpatients (n = 30) | Six infusionsb 0.5 mg/kg | Midazolam | Parallel Arm | Unspecified (no requirement) | Active suicidal/homicidal ideation, lifetime history of psychotic or bipolar disorder, current anorexia or bulimia, alcohol/substance use disorder in previous 3 months, history of recreational ketamine/PCP use >1x or any in the past 2 years, current long-acting benzodiazepine or opioid medication. | Stable meds continued | MADRS |
Feder #2 [55] | US | PTSD outpatients (n = 41) | Single infusion 0.5 mg/kg | Midazolam | Crossover | Unspecified (no requirement) | Active suicidal/homicidal ideation, lifetime history of psychotic or bipolar disorder, current bulimia or anorexia, alcohol/substance abuse/dependence in previous 3 months. | Unmedicated/washout period | MADRS |
US | Inpatients with MDD or BPI, II, or NOS w/ current MDE and suicidal ideation (n = 96) | Single Infusion 0.5 mg/kg | Midazolam | Parallel Arm | Unspecified (no requirement) | ECG abnormalities, current psychosis, history of drug or alcohol dependence within 6 months, suicidality due to substance use or withdrawal | Stable meds continued | HRSDc | |
Mathew, Murrough [58] | US | MDD outpatients (n = 73) | Single Infusion 0.5 mg/kg | Midazolam | Parallel Arm | 3 | Suicide/homicide risk, history of bipolar disorder, psychotic symptoms, and substance abuse within previous 2 years of enrollment | 1 week unmedicated washout (4 weeks for fluoxetine), except for stable nonbenzodiazepine hypnotics | MADRS |
McLoughlin, Gallagher [59] | Ireland | MDD or BP inpatients (n = 25) | Four infusionsb 0.5 mg/kg | Midazolam | Parallel Arm | Unspecified (no requirement) | Current involuntary admission, active SI, dementia, history of Axis 1 diagnosis other than a MDE, ECT within 2 months or alcohol/substance dependence within 6 months of enrollment | Stable meds continued | HRSDc |
Murrough [60] | US | Any non-exclusionary diagnosis Inpatient and Outpatient (n = 24) | Single infusion 0.5 mg/kg | Midazolam | Parallel Arm | Unspecified (no requirement) | Outpatients excluded with CSSRS score of 4 or 5, lifetime history of schizophrenia or primary psychotic disorder, current psychotic or manic symptoms, substance use disorder within 1 month of screening or positive urine tox, any lifetime abuse of ketamine or PCP | Stable meds continued | MADRS |
New Zealand | MDD outpatients (n = 30) | Single infusion as a 0.25 mg/kg bolus followed by a 0.25 mg/kg/hr infusion for 45 minutes for a total dose of 0.4375 mg/kg | Remifentanil | Crossover | 2 | Lifetime history of ketamine or PCP abuse, body weight <50 kg or >120 kg, any relevant psychiatric/neurological comorbidities including schizophrenia, psychosis, epilepsy, substance abuse/dependence, or acute suicidality | Stable meds continued | MADRS | |
Papakostas, Fava [29] | US | MDD Outpatients (n = 61) | Single infusion 0.1d, 0.2d, 0.5, or 1.0 mg/kg | Midazolam | Parallel Arm | 2 | Failure to achieve satisfactory response to >7 adequate ADM trials in the current major depressive episode, primary dx of Axis I disorder other than MDD, substance abuse/dependence within 6 months of screening, any history of ketamine or PCP use | Stable meds continued | MADRS, HRSD |
Phillips [47] | Canada | MDD outpatients (n = 43) | Single infusion 0.5 mg/kg; followed by up to 10 open-label infusionsb | Midazolam | Crossover | 2 ADMs plus 2 augmentation strategies | History of substance abuse/dependence, BMI ≥ 35, history of mania/hypomania | Stable meds continued | MADRS |
Shiroma [48] | US | MDD outpatients (n = 54) | One or six infusionsb 0.5 mg/kg | Midazolam | Parallel Arm | 2 | PTSD, mild to moderate TBI, psychosis-related disorder, bipolar disorder, and Axis 1 disorder other than MDD as primary presenting problem, history of alcohol/substance abuse within 6 months of screening, imminent suicide/homicide risk | Stable meds continued | MADRS |
Šóš [63] | Czech Republic | MDD inpatients (n = 27) | Single infusion; loading dose of 0.27 mg/kg for the first 10 min, followed by a maintenance infusion of 0.27 mg/kg within 20 min | Saline | Crossover | Unspecified (no requirement) | Suicide risk, any current psychiatric comorbidity on Axis I and II, lifetime history of psychotic symptoms and psychotic disorder in first- or second-degree relatives | Stable meds continued | MADRS |
Su, Chen [30] | Taiwan | MDD outpatients (n = 48) | Single Infusion 0.5 mg/kg or 0.2 mg/kgd | Saline | Parallel Arm | 2 | History of bipolar disorder, psychotic symptoms, and substance dependence | Stable meds continued | MADRS, HRSD |
Tiger, Lundberg [13] | Sweden | MDD outpatients (n = 30) | Up to four infusionsb 0.5 mg/kg | Saline | Parallel Arm | 1 | No medications taken for current MDE, any antidepressant treatment response, BP disorder, psychosis, neurodevelopmental disorders, any comorbid primary diagnoses, body weight >100 kg, substance abuse, current suicidality | Unmedicated/washout period | MADRS |
US | Bipolar (I or II) depressed inpatients (n = 39) | Single infusion 0.5 mg/kg | Saline | Crossover | 1 | Current psychotic symptoms or lifetime psychotic disorder, active suicidal ideation (MADRS Suicide item > 4), substance abuse/dependence within 3 months of enrollment | 2 weeks unmedicated washout period, except for one mood stabilizer at stable dose | MADRS, HRSD | |
Zarate, Ballard #2 [40] | US | MDD inpatients (n = 22) | Single infusion 0.5 mg/kg | Saline | Crossover | 1 | Current psychotic symptoms or lifetime psychotic disorder, active suicidal ideation (MADRS Suicide item > 4), substance abuse/dependence within 3 months of enrollment | 2 weeks unmedicated washout period | HRSDc |
Zarate, Ballard #3 [65] | US | MDD or bipolar (I or II) depressed inpatients (n = 40) | Single infusion 0.5 mg/kg | Saline | Crossover | 1 | Current psychotic symptoms or lifetime psychotic disorder, active suicidal ideation (MADRS Suicide item > 4), substance abuse/dependence within 3 months of enrollment | 2 weeks unmedicated washout period, except for one mood stabilizer at stable dose (bipolar patients only) | MADRS, HRSD |
