Stage I: failure of 1 AD of 1 major class of AD Stage II: failure of 2 AD of at least 2 different classes of ADs Stage III: Stage II plus failure of a TCA Stage IV: Stage III plus failure of a MAOI Stage V: Stage IV plus a course of bilateral ECT
Stage A, nonresponder: nonresponse to 1 AD or ECT with a trial duration of 6 to 8 weeks (score = 1) Stage B, TRD: TRD1, resistance to 2 or more ADs of different classes for at least 12- to 16-week duration (score = 2) TRD2, resistance to 2 or more ADs of different classes for at least 18- to 24-week duration (score = 3) TRD3, resistance to 2 or more ADs of different classes for at least 24- to 32-week duration (score = 4) TRD4, resistance to 2 or more ADs of different classes for at least 30- to 40-week duration (score = 5) TRD5, resistance to 2 or more ADs of different classes for at least 36- to 52-week duration (score = 6) Stage C, CRD: resistance to several AD trials (at least 5) including augmentation strategies (score = 7) Total score = 1 to 7
Stage I: nonresponse to each adequate (at least 6 weeks at an adequate dose) trial of an AD (1 point per trial) Stage II: optimisation of dose, optimisation of duration, and augmentation or combination of ach trial (increases overall TRD score by 0.5 for each optimisation/augmentation) Stage III: ECT used (3 points) Total score = summation of each treatment trial
Duration: acute (≤12 mnths) = 1 point; subacute (13 to 24 mnths) = 2 points; chronic (>24 mnths) = 3 points Symptom severity: subsyndromal = 1 point; mild = 2; moderate = 3; severe without psychosis = 4; severe with psychosis = 5 Treatment failures: Level 1: 1-2 ADs = 1 point Level 2: 3-4 ADs = 2 points Level 3: 5-6 ADs = 3 points Level 4: 7–10 ADs = 4 points Level 5: >10 ADs = 5 points Augmentation: not used = 0 points; used = 1 point ECT: not used = 0 points; used = 1 point Total score = 3 to 15
Stage 0: increased risk; no symptoms currently
Intervention Psychoeducation; brief cognitive skills training
Markers For example, smooth pursuit eye movements, mismatch negativity,
Stage 1a/b: mild or nonspecific symptoms or mild functional change or ultrahigh-risk.
Psychoeducation; CBT; substance use reduction; antidepressants
For example, folate status, HPA axis dysregulation
Stage 2: first episode. Moderate to severe severity and functional decline
Psychoeducation; CBT; substance use reduction; antidepressants
Continue with markers of illness state and progression
Stage 3a: incomplete remission from first episode. Could fast track to Step
As for 2 with emphasis on medical and psychosocial strategies to achieve remission
Continue with markers of illness state and progression
Stage 3b: recurrence or relapse or residual symptoms
As for 3a with emphasis on relapse prevention and early warning signs of relapse
Continue with markers of illness state and progression
Stage 3c: multiple relapses
As for 3b with emphasis on long-term stabilization
Continue with markers of illness state and progression
Stage 4: Severe, persistent or unremitting illness
As for 3c, but with emphasis on augmentation strategies
Continue with markers of illness state and progression
(i) No definition of dose/duration of trials (ii) Ranks antidepressant classes hierarchically (iii) Ordinal staging
(i) TRD stages and the distinction between TRD and CRD are arbitrarily chosen based on trial duration and number of treatment failures (ii) Ordinal staging
(i) Each trial is scored individually resulting in a continuous scale with no maximum total (ii) No antidepressant hierarchy (iii) Incorporates augmentation and ECT
(i) Multidimensional model includes illness duration, severity, augmentation and ECT (ii) No antidepressant hierarchy (iii) Continuous staging
(i) Entire illness progression staged (ii) Biomarkers incorporated (although does not include genetic or neurobiological markers) (iii) Targeted interventions for each stage
