What are the classifications of Treatment-Resistant Depression (TRD)?

Classifications of Treatment-Resistant Depression (TRD)

Five validated staging models exist to classify TRD, with the Maudsley Staging Method (MSM) being the preferred instrument as it is the only model with prospectively validated predictive utility. 1

Primary Staging Models

1. Antidepressant Treatment History Form (ATHF)

• Scoring method: Sum score based on points assigned for treatment characteristics 1
• Stages: Five stages (0–5) 1
• Key features:
  • Defines adequate treatment as ≥4 weeks duration 1
  • Does not directly correspond with number of treatment failures 1
  • Does not count psychotherapy in failed trials 1
• Validation: Predictive validity confirmed in three prospective ECT studies; reliability demonstrated as good in two studies 1

2. Thase and Rush Staging Model (TRSM)

• Scoring method: Categorical stages with higher numbers indicating greater treatment resistance 1
• Stages: Five stages (1–5) 1
• Key features:
  • Stages patients according to number of antidepressant classes that failed 1
  • Stage II corresponds with two treatment failures 1
  • Considers class hierarchy from frequently used (SSRIs, TCAs) to less common therapies (MAOIs, ECT) 1
  • Does not consider psychotherapy failures 1
• Validation: Predictive value has not been systematically assessed; reliability has not been tested 1

3. European Staging Model

• Scoring method: Based on number of weeks with treatment resistance 1
• Categories: Three distinct groups 1:
  • Nonresponders (failed one treatment)
  • TRD (failed two treatments with different antidepressant classes)
  • Chronic Resistant Depression (CRD) - resistance beyond 12 months 1
• Key features: All TRD stages require minimum of two treatment failures 1
• Validation: Predictive value and reliability have not been tested 1

4. Massachusetts General Hospital Staging Model (MGH-s)

• Scoring method: Continuous point-based score reflecting level of treatment resistance 1
• Stages: Three stages based on number of antidepressant failures, plus three points for ECT failure 1
• Key features:
  • Primarily based on number of prior antidepressant failures without class hierarchy 1
  • Considers treatment optimization, augmentation/combination strategies, and prior failed ECT 1
  • Defines adequate treatment as ≥6 weeks 1
  • No direct correspondence with two or more treatment failures 1
• Validation: Retrospective chart review showed association between higher MGH-s score and worse outcome; one retrospective study showed MGH-s predicted nonremission better than TRSM 1

5. Maudsley Staging Method (MSM) - Preferred Model

• Scoring method: Single comprehensive score ranging from 3 to 15 1
• Key features:
  • Considers number of treatment failures, augmentation strategies, and ECT 1
  • Uniquely includes disease characteristics: duration of illness and symptom severity at baseline 1
  • Most comprehensive assessment incorporating both treatment history and clinical presentation 1
• Validation: Only model with prospective validation demonstrating good predictive validity 1; two studies showed MSM score predicted future nonresponse significantly better than TRSM 1
• Consensus recommendation: Identified as the preferred instrument to assess TRD status with 69% expert consensus 1

Comparative Strengths and Limitations

Critical distinction: The MSM stands apart as the only staging model validated with prospective data, making it the most evidence-based choice for clinical practice and research 1. The ATHF demonstrates good reliability and predictive validity specifically for ECT outcomes 1, while the TRSM, European Model, and MGH-s lack systematic validation studies 1.

Common pitfall: None of these models have established reliability testing except the ATHF 1. When selecting a staging model, feasibility may guide choice in the absence of a universally mandated approach 1.

Practical Application

For clinical trials: The MSM is recommended as the preferred staging instrument 1. For clinical practice, either careful treatment history documentation or structured staging tools (ATHF, TRSM, European Model, MGH-s, or MSM) can confirm treatment resistance, with selection based on feasibility 1.