Magnitude of the Placebo Response Across Treatment Modalities Used for Treatment-Resistant Depression in Adults, 2021, Jones et al

A Systematic Review and Meta-analysis


Key Points

Question What is the placebo effect magnitude in different treatment modalities used for management of patients with treatment-resistant depression?

Findings In this systematic review and meta-analysis of 3228 patients with treatment-resistant depression in 50 randomized clinical trials, the placebo effect size was large and consistent across treatment modalities. Response and remission rates associated with placebo effect were comparable across modalities.

Meaning The findings of this study suggest a placebo effect size benchmark may be used to interpret the findings of past and future clinical trials.

Results Fifty RCTs were included involving various types of placebo or sham interventions with a total of 3228 participants (mean [SD] age, 45.8 [6.0] years; 1769 [54.8%] female). The pooled placebo effect size for all modalities was large (g = 1.05; 95% CI, 0.91-1.1); the placebo effect size in RCTs of specific treatment modalities did not significantly differ. Similarly, response and remission rates associated with placebo were comparable across modalities. Heterogeneity was large. Three variables were associated with a larger placebo effect size: open-label prospective treatment before double-blind placebo randomization (β = 0.35; 95% CI, 0.11 to 0.59; P = .004), later year of publication (β = 0.03; 95% CI, 0.003 to 0.05; P = .03), and industry-sponsored trials (β = 0.34; 95% CI, 0.09 to 0.58; P = .007). The number of failed interventions was associated with the probability a smaller placebo effect size (β = −0.12; 95% CI, −0.23 to −0.01, P = .03). The Egger test result was not significant for small studies’ effects.

Conclusions and Relevance This analysis may provide a benchmark for past and future clinical RCTs that recruit patients with TRD standardizing an expected placebo effect size.


https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784479

 

Looks like within-arm comparisons are all the rage, likely because of how easily they allow uninterpretable results to be interpreted in whatever direction whoever tipped the scale wanted it to tip. Especially on commonly misdiagnosed vague issues that are notoriously subject to natural improvement. It's kind of amazing that physicians can still criticize alternative medicine for doing the same thing they do with the same intent, even more so that they don't realize it at all because of the incentives, so many incentives to cheat, so few reasons not to.

Also if you "calibrate" useless instruments with one another with the same intent, it can be argued that the same instruments give the result they intended to produce. Somehow I'm not sure how almost no one sees a problem with that, especially as it was essentially the original problem that forced the scientific method into adoption.

https://twitter.com/user/status/1442207389483163649

 

It seems not to be common knowledge that not only is this standard practice in psychosomatic "medicine", it's literally all there ever is because active interventions can't be controlled so they are all technically sort of within-group. It's hard to tell because when you point this out most people have excuses for why it's OK in this context, even though everyone recognizes that it's supposed to be a standard, and thus not open to exceptions.

Some standards are more standard than others, it seems.

https://twitter.com/user/status/1441604367572951041


("a study showing that placebo effects can be meaningful for any health condition" is literally the entire "evidence" base for psychosomatic "medicine", it literally only exists in this non-standard space where standards don't apply)