What is the protocol for the ADEPP (Antidepressants for the Prevention of Depression following First‑Episode Psychosis) trial evaluating sertraline versus placebo in patients aged 16–65 years who had a first‑episode psychosis 3–12 months ago, are currently in remission, have no major depressive episode, and are not on an antidepressant?

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ADEPP Study Protocol Summary

Study Design and Rationale

The ADEPP (Antidepressants for the Prevention of Depression following First-Episode Psychosis) trial is a multi-centre, double-blind, randomised, placebo-controlled trial investigating whether sertraline 50 mg daily can prevent depression in patients recovering from first-episode psychosis. 1

The trial addresses a critical clinical gap: more than 40% of people develop depressive episodes after first-episode psychosis, contributing to poor outcomes, increased morbidity and mortality, and substantial healthcare costs. 1

Eligibility Criteria

Inclusion Criteria

  • Age: 16–65 years (protocol states 18–65 in abstract, but expanded question specifies 16–65) 1
  • Timing: 3–12 months post-treatment initiation for first-episode psychosis 1
  • Clinical status: Currently in remission from psychotic symptoms 1
  • Depression status: No current major depressive episode at enrollment 1
  • Medication status: Not currently taking an antidepressant 1

Key Exclusion Criteria

  • Active major depressive episode at time of enrollment 1
  • Current antidepressant use 1

Intervention Protocol

Treatment Arms

  • Active arm: Sertraline 50 mg orally once daily for 6 months 1
  • Control arm: Matched placebo once daily for 6 months 1
  • Background therapy: All participants continue treatment as usual (typically antipsychotic medication) 1

Duration

  • Intervention phase: 6 months of double-blind treatment 1
  • Follow-up: Outcomes assessed throughout the 6-month intervention period 1

Outcome Measures

Primary Outcome

  • Number of new cases of depression comparing sertraline versus placebo arms over the 6-month intervention phase 1

Secondary Outcomes

  • Suicidal behaviour 1
  • Anxiety symptoms 1
  • Rates of psychotic relapse 1
  • Functional outcome 1
  • Quality of life 1
  • Healthcare resource utilization (for cost-effectiveness analysis) 1

Sample Size and Statistical Power

  • Target recruitment: 452 participants 1
  • This sample size was calculated to detect clinically meaningful differences in depression incidence between treatment arms 1

Rationale for Sertraline Selection

Evidence Base

  • Sertraline has demonstrated safety when co-prescribed with antipsychotic medications, which is essential since all participants will be receiving ongoing antipsychotic therapy 1
  • Evidence supports sertraline's efficacy for treating depression in established schizophrenia 1
  • Sertraline is a selective serotonin reuptake inhibitor (SSRI) and represents a common first-line medication for depression treatment in adults 1

Dosing Justification

  • The 50 mg daily dose represents a standard starting and maintenance dose for depression prevention 1, 2
  • Previous prophylactic trials demonstrated that sertraline 50 mg daily significantly reduced recurrence rates (16.8%) compared to placebo (33.3%) in patients with highly recurrent depression 2

Clinical Context and Significance

Why Prevention Matters

  • Depression after first-episode psychosis substantially worsens functional outcomes and increases suicide risk 1
  • Early intervention in the critical period following first-episode psychosis may prevent the cascade of complications associated with depressive episodes 1
  • Reducing depression incidence could improve long-term recovery trajectories and reduce healthcare costs 1

Novel Aspects of the Trial

  • Unlike previous antidepressant maintenance trials that used the same medication from acute through maintenance phases, ADEPP enrolls patients who are not currently depressed, testing true prophylactic efficacy 1, 2
  • The trial specifically targets the high-risk period 3–12 months after first-episode psychosis, when depression risk is elevated 1

Safety Monitoring

Known Safety Profile

  • Sertraline has been extensively studied and shows acceptable tolerability when combined with antipsychotics 1
  • The trial will monitor for adverse events, including suicidal behaviour, which is tracked as a secondary outcome 1

Trial Registration and Status

  • Registration: ISRCTN12682719, registered 24 November 2020 1
  • Status: Protocol published 2023; trial designed to test clinical utility, acceptability, and cost-effectiveness 1

References

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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