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. 2022 Sep 7;27(12):5096–5112. doi: 10.1038/s41380-022-01757-7

Table 2.

Moderators included in pooled dataset.

Domain Sources of Information Harmonized Variable(s) % available N available Tier/Analysis Summary statistics and case counts
Study design features Study methods
Study Placebo Type 100.00 720 Tier 1a n = 477 psychoactive; n = 243 inert
Crossover or Parallel Arm 100.00 720 Tier 1a n = 242 crossover; n = 478 parallel
Psychiatric diagnoses (principal and comorbid) Patient-level text and ICD/DSM codes; study-level inclusions/exclusions Dummy-Coded diagnoses:
Principal Diagnosis 100.00 720 Tier 1b n = 579 MDD; n = 66 BD; n = 74 PTSD; n = 1 Borderline Personality Disorder
Major Depressive Disorder (MDD) 100.00 720 Tier 1b n = 627 yes; n = 93 no
Bipolar (I or II) Disorder 99.44 716 Nonec n = 66 yes; n = 650 no
Post-traumatic Stress Disorder 72.50 522 Tier 2, M* 2d n = 118 yes; n = 365 no
Any Anxiety Disorder 72.36 521 Tier 2, M* 2d n = 285 yes; n = 236 no
Generalized Anxiety Disorder 64.58 465 Tier 2 n = 101 yes; n = 364 no
Social Anxiety Disorder 58.06 418 Tier 2 n = 99 yes; n = 319 no
Obsessive-Compulsive Disorder 57.92 417 Tier 2 n = 18 yes; n = 399 no
Panic Disorder 57.78 416 Tier 2 n = 51 yes; n = 365 no
Agoraphobia 57.78 416 Tier 2 n = 36 yes; n = 380 no
Substance Use Disorder (lifetime) 42.92 309 Tier 2 n = 26 yes; n = 283 no
Alcohol Use Disorder (lifetime) 40.28 290 Tier 2 n = 66 yes; n = 224 no
Eating Disorder 36.11 260 None n = 9 yes; n = 251 no
Dysthymia 30.69 221 None n = 31 yes; n = 190 no
Any Pain Disorder 30.28 218 None n = 48 yes; n = 170 no
Attention-Deficit Disorder 27.64 199 None n = 9 yes; n = 190 no
Specific Phobia 26.94 194 None n = 21 yes; n = 173 no
Any Personality Disorder 25.42 183 None n = 49 yes; n = 134 no
Borderline Personality Disorder 24.31 175 None n = 20 yes; n = 155 no
Demographics Patient-level integers, text, and coded variables
Age 99.72 718 Tier 1b mean = 42.4; SD = 13.3; range = 18–72
Female or Male 99.58 717 Tier 1b n = 386 yes; n = 331 no
Years of Education 74.44 536 Tier 2, M* 2 g mean = 14.6; SD = 2.9; range = 4–25
Marital Status 50.83 366 Tier 2, M* 2 g n = 127 married (or equivalent); n = 151 single/never married; n = 57 divorced or separated; n = 6 widowed; n = 25 not married (not further specified)
Income Level/Range 15.83 114 None n = 46 $0–25 K; n = 33 $25-50 K; n = 10 $50-70 K; n = 25 > $70 K
Race, Ethnicity, Culture Patient-level text and coded variables
Study Performed in the US (y/n) 100.00 720 Tier 1b n = 480 yes; n = 240 no
EthnoRacial Category 89.58 645 Tier 2, M* 2a n = 469 non-Hispanic white; n = 61 Black; n = 66 Asian; n = 26 Hispanic; n = 14 more than one race; n = 9 other non-White
Hispanic/Latinx (y/n) 72.22 520 Tier 2 n = 29 yes; n = 491 no
Depression course and characteristics Patient-level integers and coded variables; study-level inclusions/exclusions
Inpatient vs. Outpatient 100.00 720 Tier 1b n = 461 outpatient; n = 259 inpatient
Study-level TRD Threshold 100.00 720 Tier 1b n = 280 no criterion; n = 71 1 failure; n = 253 2 failures; n = 16 ≥ 3 failures
Suicidality severity at baseline (MADRS item 10) 70.42 507 Tier 2 mean = 2.01; SD = 1.5; range = 0–6
Duration of Current MDE (months)a 61.11 440 Tier 2, M* 2c mean = 52.5; SD = 95.7; range = 0.47–768
Recurrent MDD (y/n) 55.14 397 Tier 2, M* 2c n = 301 yes; n = 6 no
Number of Depressive Episodesa 52.64 379 Tier 2, M* 2c mean = 8.0; SD = 10.7; range = 1–78
Age of illness onset 48.8 351 Tier 2 mean = 23.7; SD = 12.2; range = 4–60
Number of failed ADM trials (patient-level) 42.78 308 Tier 2 mean = 4.44; SD = 2.3; range = 1–14
Childhood trauma questionnaire (or any other available measure of childhood trauma) 20.3 146 None mean = 56.4; SD = 22.4; range = 0–119
Concurrent Medications and Substances Patient-level integers and coded variables; study-level inclusions/exclusions
Any Concurrent Psych Med (y/n) 76.25 549 Tier 2, M* 2b n = 262 yes; n = 287 no
Any Benzodiazepine (y/n) 65.56 472 Tier 2, M* 2b n = 42 yes; n = 430 no
Number of Concurrent Psych Meds 51.53 371 Tier 2 mean = 0.30; SD = 0.61; range = 0–3
Smoker (Dummy-Coded) 53.47 385 Tier 2, M* 2 f n = 109 yes; n = 76 no
Biological measurements Patient-level integers
Ketamine dose (mg) 82.64 595 Tier 2 Ketamine arms only: mean = 42.1; SD = 15.4; range = 18.5–100.7b
Dosing weight (kg)a 60.83 438 Tier 2 mean = 79.03; SD = 19.8; range = 35–174
BMIa 55.56 400 Tier 2, M* 2 f mean = 27.23; SD = 6.2; range = 17–60.8
Systolic Blood Pressure 53.89 388 Tier 2, M* 2e mean = 121.49; SD = 14.3; range = 86–166
Diastolic Blood Pressure 53.89 388 Tier 2, M* 2e mean = 75.24; SD = 10.2; range = 48–112
Baseline Pulsea 52.22 376 Tier 2 mean = 70.89; SD = 12.7; range = 43–164
Baseline serum BDNF level (ng/mL) 16.90 122 None mean = 921.72; SD = 1629.1; range = 0 9419
Baseline Pulse-Ox 17.60 127 None mean = 97.77; SD = 1.9; range = 90–100
Baseline Respiration Rate 10.83 78 None mean = 15.44; SD = 3.6; range = 5–28

aTier 1 variables are those available in >99% of patients in the pooled dataset. These first two Tier 1 variables, which related to study design features rather than to patient-level characteristics, were excluded from all combined moderator analyses, as the purpose was to identify combinations of patient (not study) characteristics that predicted differential improvement following ketamine (relative to placebo).

bTier 1 variables are those available in >99% of patients in the pooled dataset. These 7 Tier 1 variables were related to patient-level characteristics and thus were included in the Tier 1 M*, and also retained in all M* analyses across all Tiers 2a-f, as their inclusion never reduced the number of studies/patients available for any analysis and could only increase predictive power for the data-driven approach.

cBipolar I/II diagnosis was highly non-orthogonal and virtually redundant with the MDD diagnosis variable, as bipolar and unipolar depression diagnoses are mutually exclusive. To eliminate this redundancy in hypothesis tests, this variable was not tested as a moderator in any analysis.