Defining treatment-resistant depression

Area of Science:

• Psychiatry
• Clinical Research Methodology

Background:

• Varying conceptualizations of treatment-resistant depression (TRD) complicate the translation of research into clinical practice guidelines.
• Inconsistent definitions hinder the development of standardized treatment protocols and evidence-based care.

Purpose of the Study:

• To clarify expert and investigator definitions of TRD.
• To systematically review the alignment of TRD definitions in clinical trials with expert consensus.

Main Methods:

• Conducted a review for the Centers for Medicare & Medicaid Services and the Agency for Healthcare Research and Quality.
• Systematically reviewed clinical trial definitions of TRD up to July 5, 2019.

Main Results:

• No consensus definition for TRD was identified.
• Common definitions required 1-2 prior treatment failures, but adequacy of dose/duration lacked consensus.
• Only 17% of studies met the most common TRD criteria; functional impairment and quality-of-life measures were rarely used.

Conclusions:

• Developing a consensus definition for TRD, including prior treatment failures and adequacy of dose/duration, is critical.
• Establishing a core package of standardized outcome measures is essential for advancing TRD research.
• Improved research design and conduct will lead to clearer clinical guidelines for treating TRD.