Declining differences in response rates with antidepressants versus placebo: a modest proposal for another...

Area of Science:

• Pharmacology
• Clinical Trials
• Psychiatry

Background:

• Observed decline in response rates for sequential selective serotonin reuptake inhibitor (SSRI) drug trials compared to placebo.
• Existing literature often attributes this to increasing placebo response rates.

Purpose of the Study:

• To propose an alternative explanation for declining SSRI response rates: an order effect.
• To investigate the impact of sequential drug introductions within a therapeutic class on clinical trial outcomes.

Main Methods:

• Conceptual analysis of clinical trial data trends.
• Literature review focusing on SSRI and placebo response rates.
• Examination of drug class introduction timelines and participant pools.

Main Results:

• Response rates in SSRI trials appear to decline as a function of the number of previously introduced SSRIs.
• This trend suggests that the pool of likely responders diminishes with each new agent in a class.

Conclusions:

• An order effect, where prior treatment within a drug class reduces the pool of available responders, is a plausible explanation for declining SSRI trial response rates.
• This phenomenon is likely applicable to other drug classes with a shared mechanism of action (MOA).