Monday, August 25, 2025

What evidence do we have so far for the Zoloft and rexulti for PTSD? (ChatGPT, 2025-8-25)

意思是說,好一點之後,rexulti 就可以撤,留下 Zoloft 即可,


Here’s what current evidence tells us about Zoloft (sertraline) and Rexulti (brexpiprazole) for treating PTSD:





Zoloft (Sertraline)




1. Official Status & Guidelines



  • Zoloft is FDA‑approved for PTSD and considered a first-line pharmacological treatment, alongside Paroxetine  .
  • Clinical practice guidelines (e.g., APA, VA/DoD) recognize SSRIs—especially Sertraline and Paroxetine—as having the most robust evidence from randomized controlled trials  .




2. Effectiveness



  • A meta-analysis of 21 PTSD trials (2021) supports the efficacy of SSRIs like sertraline, with an estimated treatment response rate of 50–60%  .
  • According to Wikipedia, sertraline produces modest improvements, particularly in cases of sexual or physical assault in women, though results in men may be less robust  .
  • In pooled trials across multiple indications (not just PTSD), sertraline showed significant improvement over placebo, supporting its broader efficacy  .




3. Summary



  • Conclusion: Zoloft is evidence-supported and guideline-recommended for PTSD, typically yielding modest to moderate symptom reduction.
  • Limitations: It helps many, but a substantial portion of patients (~40–60%) may not respond fully  .
  • Best Use: Often paired with trauma-focused psychotherapy (TF‑CBT), which remains the gold standard treatment  .






Rexulti (Brexpiprazole)

 — Particularly in Combination with Sertraline




1. Recent Clinical Trial Data



  • Combination therapy trial (2025): A Phase 3 randomized, double-blind trial showed that brexpiprazole + sertraline led to a statistically significant reduction in PTSD symptoms (CAPS-5 score improvement of –19.2 vs –13.6; p < .001)  .
  • The combination was generally well-tolerated, with side effects consistent with known brexpiprazole profiles  .




2. Regulatory Status & Controversy



  • FDA Panel Decision (2025): An FDA advisory committee voted 10‑1 against recommending approval of the brexpiprazole + sertraline combination for PTSD. Reasons included inconsistent results and modest clinical benefit  .
  • Notably, although one late-stage trial was positive, another failed to show significant difference from sertraline alone  .




3. Summary



  • Conclusion: The brexpiprazole + sertraline combination shows preliminary promise but lacks sufficient consistent evidence for approval. More studies and replication are needed.
  • Note: As of now, Rexulti remains off-label for PTSD, pending clearer regulatory outcomes.






Quick Comparison

Medication / Strategy

Evidence Quality

FDA Status

Notes

Zoloft (sertraline)

Strong RCT support, meta-analyses

FDA-approved

Modest efficacy; standard first-line

Rexulti + Sertraline (combo)

Promising Phase 3 results

Not yet approved

Mixed trial outcomes; pending FDA review

Rexulti monotherapy

Little to no evidence

Off-label

Not studied as a stand-alone PTSD agent





Bottom Line



  • Zoloft remains a validated, guideline-backed treatment for PTSD, effective for many though not all.
  • Rexulti plus Zoloft offers a hopeful possibility—but currently lacks enough consistent, compelling results to earn regulatory approval.
  • For best outcomes, psychotherapy (particularly trauma-focused CBT) paired with medications like Zoloft continues to be the core recommendation.



Further reading


https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-advisers-vote-against-otsukas-ptsd-combination-treatment-2025-07-18/?utm_source=chatgpt.com