DEPRE'5sion

🔍 DEPRE’5 Study Overview

A pragmatic, assessor-blinded, multi-centre randomized controlled trial compared five treatment strategies over 6 weeks in patients with Major Depressive Disorder who had not responded to an SSRI:

1. SSR‑I dose optimization (SSRI‑Opt)

2. Lithium augmentation of SSRI (SSRI + Li)

3. Nortriptyline combination (SSRI + NTP)

4. Switching to venlafaxine (VEN)

5. SSRI + Problem-Solving Therapy (SSRI + PST) clinicaltrials.gov+11researchgate.net+11cambridge.org+11

📊 Key Findings

Second-line approaches (excluding SSRI‑Opt) vs Dose Optimization:

• Greater response rates: 28.2% vs 14.3% (OR = 2.36, 95% CI 1.0–5.6; p = 0.05)

• Larger average HRDS‑17 improvement: –2.6 points (95% CI –4.9 to –0.4; p = 0.021) researchgate.net+1cambridge.org+1

Most consistent (though only marginally significant) benefits:

• Venlafaxine switch:

  • OR for response ≈ 2.53 (95% CI 0.94–6.80; p = 0.067)

  • HDRS‑17 decrease ≈ –2.7 points (95% CI –5.5 to 0.0; p = 0.054) en.wikipedia.org+15researchgate.net+15pubmed.ncbi.nlm.nih.gov+15

• SSRI + PST (psychotherapy):

  • OR ≈ 2.46 (95% CI 0.92–6.62; p = 0.074)

  • HDRS‑17 drop ≈ –3.1 points (95% CI –5.8 to –0.3; p = 0.032) sciencedirect.com+5researchgate.net+5pubmed.ncbi.nlm.nih.gov+5

Adverse effects:

• Lowest in the SSRI + PST group (~28% mild)

• Highest in SSRI + NTP (~75%), though mostly mild psychiatryai.com+14researchgate.net+14pubmed.ncbi.nlm.nih.gov+14

✅ Conclusions

• Patients who don’t adequately respond to an SSRI typically benefit from a second-line strategy, rather than simply optimizing the SSRI dose.

• Switching to venlafaxine or adding problem-solving psychotherapy showed the greatest consistent benefit, despite limited statistical power.

• Based on safety and tolerability, SSRI + PST may be the most balanced option.

💡 Clinical Implication

If an SSRI fails initially, rather than increasing the dose, consider either:

• Switching to an SNRI (like venlafaxine)

• Or adding structured psychotherapy, such as problem-solving therapy

These strategies are supported both by clinical efficacy and tolerability data.

https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/abs/depre5-study-pragmatic-multicentre-fivearm-parallelgroup-randomised-controlled-trial-with-blinded-assessment-to-compare-treatment-strategies-in-major-depression-after-a-failed-selective-serotonin-reuptake-inhibitor-treatment/12C2AADD33C0DD86A4C03C99560A1180