Background: Appropriate control conditions in psychotherapy trials have long been a focus of much discussion. Broadly speaking we may think of three categories: (i) placebo interventions (ii) no treatment, and (iii) treatment as usual. Waiting list, on which the participants do not receive the treatment until after the trial is over, is usually regarded as a form of no treatment. For example, when Hrobjartsson and Gotzsche meta-analyzed the magnitude of placebo effect, they compared placebo interventions against both no treatment control (NTC) and waiting list control (WLC) indiscriminately [1]. However, there is growing suspicion that NTC and WLC may be substantively different as a control condition.

Objectives: To assess the difference in the effect sizes of NTC and WLC in psychotherapy trials.

Methods: We have been conducting a systematic review of all available evidence for all psychological therapies for treating depression. This corollary study applied random-effects Bayesian network meta-analysis on the quadrangular network of cognitive-behavior therapy (CBT: the best researched of all psychotherapies for depression), psychological placebo (PP), NTC and WLC.

Results: The comparison CBT vs WLC showed extreme funnel plot asymmetry. After excluding 12 studies contributing to this asymmetry, the consistency model showed adequate fit to the data (41 studies). CBT consistently beat PP (OR for response: 1.6, 95%CrI: 0.92–2.6), NTC (2.2, 1.5–3.3) and WLC (3.0, 2.1–4.3) in this order. The comparison between NTC and WLC was not statistically significant (1.3, 0.8–2.3).

Conclusions: The effect size of CBT against WLC was consistently but non-significantly bigger than that against NTC. The effectiveness of CBT, and other psychosocial interventions, may be overestimated if WLC was used as a control condition.

Reference

1. Hrobjartsson A, Gotzsche PC. Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. NEJM. 2001;344:1594–602.