Some exploratory evidence that wait-list conditions may act as a nocebo in psychotherapy trials

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The double-blinded placebo-controlled randomized trial have long been held as the gold standard in pharmacological research. Unfortunately, this design is impossible to mimic in clinical psychology. Even if we — at best — could try to keep the participants blinded to their treatment allocation, it would be rather hard to blind therapists to what therapy they are giving. The design of a placebo condition is — albeit not impossible — very tricky, and no real consensus exists regarding what a placebo condition should look like in psychotherapy trials. Consequently, wait-list conditions are commonly used — even though they have been hotly debated for a long time (Boot, 2013; Mohr, 2009). It is generally acknowledge that waiting-lists provide weaker control over treats to the study´s internal validity, compared to “placebo”-conditions or active treatments. It is also generally acknowledge that contrasting treatments to wait-lists will yield inflated effect sizes (Cunningham et al., 2013). I would also say that the notion is fairly well spread that wait-lists could act as a nocebo. Some evidence exists that participants put on wait-lists continue to improve during the waiting phase (Devilly, 2009; Hesser et al, 2011). However, the big question is whether this improvement is less than what would be expected to occur naturally if no treatment were received. The general theory is that being put on a wait-list will make it less likely that you would perform certain behaviors that you would have done otherwise. In the context of treating depression this could manifest as patients failing to muster the energy to do fun and reinforcing activities, since they know that they will be offered treatment soon where they will get a change to adress their problems.

This hypothesis that wait-lists could be nocebo conditions was investigated by Furukawa et al (2014). The authors performed a network meta-analysis, which seem to be quickly becoming the new cool kid on the block in clinical psychology. What it does is it allows the researchers to compare the relative effectiveness of different interventions by using data from both direct and indirect comparisons. It is thus really useful when comparing several different control conditions, that have not all been compared in a single trial. Giving a detailed description of network meta-analysis is outside the scope of this article, however good introductions can be found in Mills et al (2013), Cipriani & Higgs (2013) and Higgins & Whitehead (1996) (given in order of required math literacy of the reader).

The network meta-analysis by Furukawa et al included three different types of control conditions: Placebo (with equivalent number of sessions and therapists’ skill level), no treatment and waiting list controls. These conditions were contrasted with cognitive-behaviour therapy (CBT) for depression, delivered either individually (face-to-face) or in group sessions. In all 49 RCTs were included in the final analysis.

The outcome was presented as odds ratios for response (50% or greater reduction in depression). Interestingly, the results did not show CBT to be superior to placebo conditions, but it was superior to no treatment (OR 95% CI: 1.3-4.3) and wait-list conditions (OR 95% CI: 3.9-10.1). This is surprising since another recent network meta-analysis found all active psychotherapies to be more effective than placebo (Barth et al, 2013). Perhaps most interestingly, Furukawa et al (2014) found that participants put on waiting lists faired less well then participants who were offered no treatment (OR 95% CI: 1.3-5.7). Meaning that they found evidence for the hypothesis that a wait-list condition could act as a nocebo. However, this is really exploratory results so we should really wait for more data before jumping to any conclusions. Furukawa TA, Noma H, Caldwell DM, Honyashiki M, Shinohara K, Imai H, Chen P, Hunot V, & Churchill R (2014). Waiting list may be a nocebo condition in psychotherapy trials: a contribution from network meta-analysis. Acta psychiatrica Scandinavica PMID: 24697518

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