New Study Shows Placebo Effect for Antidepressant Treatment Growing Stronger
Placebos have long been an integral part of medical research, serving as the gold standard for evidence in placebo-controlled trials. However, recent research has shed light on the growing strength of the placebo effect when it comes to antidepressant treatments.
A new study, building on previous findings, has revealed that the placebo effect for transcranial magnetic stimulation (TMS) is also increasing over time. TMS is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain. While effective treatments are continuing to improve, this phenomenon raises questions about the reliability of placebo-controlled trials.
Transcranial magnetic stimulation works by inducing currents in the brain, influencing neural activity in targeted areas. Despite its non-invasive nature, there are limitations to this technique, such as difficulty in targeting deep areas of the brain and imprecise targeting of specific neural processes. The effectiveness of TMS depends on various factors, including the length, intensity, and number of magnetic pulses administered.
Several clinical trials, including those for depression, have utilized placebo controls alongside TMS treatment. Placebos in these studies involve placing inactive hardware near the skull or directing the magnetic fields to stimulate areas adjacent to the skull rather than underneath it.
Over the past few decades, placebos have exhibited an interesting trend in relation to depression treatment. They have become more potent since at least the 1980s, as multiple studies have shown this phenomenon with pill-based placebos. A few studies have also hinted at the increasing potency of placebo effects in transcranial magnetic stimulation. To address this phenomenon comprehensively, researchers conducted a meta-analysis, analyzing high-quality clinical trial data from 52 studies encompassing 4,500 participants, half of whom received placebo treatments.
The study found that placebos consistently elicited improvements in participants’ conditions, though the actual treatment had a larger effect. When measured using the “response magnitude,” the placebo was rated at 24 percent, while the actual treatment scored 38 percent. To examine the changes in placebo effects over time, the researchers divided the trials into two periods, spanning 1999 to 2007 and 2018 to 2022. Both the placebo and treatment effects increased over time, but in parallel, ensuring that the changes did not skew trial outcomes.
The researchers performed a regression analysis to identify factors influencing these correlations. The analysis revealed a correlation between the placebo effect and the impact of the actual treatment. Trials conducted in North and South America and those with a higher risk of bias also tended to have larger effects.
While the placebo effect remains a significant factor, the findings suggest that changes in study design may account for some differences between earlier and later trials. The researchers noted that numerous factors, such as patient populations, TMS protocols, sham procedures, and trial methodology, have undergone significant shifts over the past two decades. These changes could influence how participants perceive the sham treatment, as the placebo effect is heavily influenced by the belief that treatment is occurring. Recent efforts to make the placebo convincing could explain the observed changes.
However, the lack of detailed reporting on placebo procedures in studies makes it challenging to pinpoint specific changes driving the increasing placebo effect.
The researchers estimate that approximately 7,500 new studies showing no placebo effect would be needed to eliminate it entirely. This highlights the complexity of the placebo phenomenon and the need for further research to understand its mechanisms fully.
The study was published in Nature Mental Health and can be accessed under the DOI: 10.1038/s44220-023-00118-9.