The overestimation of the effect sizes of psychotherapies for depression in waitlist controlled trials: a meta-analytic comparison with usual care controlled trials.

Aims: There is considerable evidence that waiting list (WL) control groups overestimate the effect sizes of psychotherapies for depression. It is not clear, however, what are the exact causes for this overestimation. We decided to conduct a meta-analytic study to compare trials on psychotherapy for depression with a WL control group against trials with a care-as-usual (CAU) control group.

Methods: We used an existing meta-analytic database of randomized trials comparing psychological treatments of adult depression with control groups and selected trials using a WL or a CAU control group. We used subgroup and meta-regression analyses to examine differences in effect sizes between WL and CAU controlled trials.

Results: We included 333 randomized controlled trials (472 comparisons; total number participants: 41,480), 141 with a WL and 195 with a CAU control group (3 included both). We found several significant differences between WL and CAU controlled trials (in type of therapy examined, treatment format, recency, target group, recruitment strategy, number of treatment arms and number of depression outcome measures). The overall effect size indicating the difference between treatment and control at post-test for all comparisons was g = 0.77 (95% confidence interval [CI]: 0.71; 0.84) with high heterogeneity (I² = 84; 95% CI: 82; 85). A highly significant difference was observed between studies with a CAU control group (g = 0.63; 95% CI: 0.55; 0.71; I² = 85; 95% CI: 83; 86) and studies with a WL (g = 0.95; 95% CI: 0.85; 1.04; I² = 80; 95% CI: 78; 82; p for difference < 0.001). This difference remained significant in all sensitivity analyses, including a meta-regression analysis in which we adjusted for all differences in characteristics of studies with a WL versus CAU control group. We also found that pre-post effect sizes in WL control conditions (g = 0.37; 95% CI: 0.28; 0.46) were significantly smaller than change within CAU conditions (g = 0.64; 95% CI: 0.50; 0.78). We found few indications that pre-post effect sizes within therapy conditions differed between WL and CAU controlled trials.

Conclusions: WL control conditions considerably overestimate the effect sizes of psychological treatments, compared to trials using CAU control conditions. This overestimation is probably caused by a smaller improvement within the WL condition compared to the improvement in the CAU condition. WL control conditions should be avoided in randomized trials examining psychological treatments of adult depression.