Placebo analgesia in physical and psychological interventions: Systematic review and meta-analysis of three-armed trials
Three pages on PainSci cite Hohenschurz-Schmidt 2024: 1. Placebo Power Hype 2. Mind Over Pain 3. A new placebo analgesia review
PainSci commentary on Hohenschurz-Schmidt 2024: ?This page is one of thousands in the PainScience.com bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided wherever possible.
Placebo’s potency has long been questioned, but we still don’t really know how much pain can be eased by faith in a treatment. This review is the first major attempt to nail that down in quite a while, and they did it by studying three-armed studies.
A “no exposure” group — where subjects get diddly squat — is needed to tease out the difference between a power-of-the-mind placebo effect from many confounders. But such studies are rare: extra arms aren’t cheap, but don’t add much value for most researchers, who aren’t studying placebo itself.
Hohenschurz-Schmidt et al found just 17 trials like this, studying people with back, neck, and other joint pain, or fibromyalgia. The treatments were “physical, psychological and self-management” — all the usual suspects, from massage to icing to TENS to mindfulness apps and cognitive behavioural therapy.
The result?
“The average short-term placebo effect was small,” right near the bottom of the scale they used. One might even say the average effect was very small. And probably also brief (although they didn’t have a lot of long-term data to work with).
Maybe the mind isn’t so mighty after all? The data didn’t seem to convince the authors!
“It may be that placebo effects are indeed less powerful than often suspected. However, the small average effect in this sample may also be due to methodological challenges present across all included RCTs, and placebo effects clearly varied in magnitude in our sample. … Various factors … may have led to an underestimation of placebo effects here.”
Maybe they are making excuses for the poor result. A weak average means that stronger placebo is probably not that strong and/or common. But there probably are good reasons to suspect that placebo analgesia can be dialed up. Manual therapists, pay attention now, you’ll like this part …
Studies of hands-on therapies generated more placebo than other kinds of treatment. More than things like, say, a disabled shockwave ultrasound device, and other controls that were less “interactive, personalized, and higher-intensity.”
“The on average larger placebo effect from manual control interventions may speak to the therapeutic potential inherent to human touch and/or to higher perceived credibility and expectations of benefits in these interventions.”
But restrain your equines: they based that on a just a few of the trials they reviewed, not enough data to actually support it. It’s just possible and plausible. We don’t know if it’s true, and it certainly doesn’t tell us how high placebo can soar in ideal conditions.
The potential potency of placebo analgesia remains unknown.
Common issues and characteristics relevant to this paper: ?Scientific papers have many common characteristics, flaws, and limitations, and many of these are rarely or never acknowledged in the paper itself, or even by other reviewers. I have reviewed thousands of papers, and described many of these issues literally hundreds of times. Eventually I got sick of repeating myself, and so now I just refer to a list common characteristics, especially flaws. Not every single one of them applies perfectly to every paper, but if something is listed here, it is relevant in some way. Note that in the case of reviews, the issue may apply to the science being reviewed, and not the review itself.
- Damned with faint praise — technically positive results (at least partially) that don’t actually impress.
original abstract †Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.
BACKGROUND: The magnitude of placebo effects from physical and psychological 'sham' is unknown but could impact efficacy trials and treatment understanding. To quantify placebo effects, this systematic review of three-armed randomised controlled trials (RCTs) of physical and psychological interventions for pain compared outcomes in 'sham' control intervention and non-exposure arms.
METHODS: RCTs with treatment, 'sham' control intervention, and non-exposure groups were included, enrolling adults with any pain. A protocol was pre-registered (PROSPERO: CRD42023413324), and twelve databases searched from 2008 to July 2023. Trial methods and blinding were analysed descriptively and risk of bias assessed. Meta-analysis of pain measures at short-, medium- and long-term was performed with random-effects models of standardised mean differences (SMD). Studies were sub-grouped according to control intervention type.
RESULTS: Seventeen RCTs were included. The average short-term placebo effect was small (0.21 SMD, 0.1-0.33 95% CI, p=0.0002, 1440 participants). It showed no heterogeneity (Tau2 =0.1, I2 =11%, p=0.3), preventing meta-regression analyses of effect modifiers. However, sub-group analyses revealed larger placebo effects in manual control interventions compared to disabled devices and miscellaneous control interventions. Overall, placebo analgesia accounted for 39% of treatments' short-term effectiveness «39% of not much.» No placebo effects were found at medium-term (7 RCTs, 381 participants) or long-term follow-up (3 RCTs, 173 participants).
CONCLUSIONS: The observed placebo analgesia has mechanistic and methodological implications, though its clinical importance may be limited. Control intervention design affects placebo effects, highlighting the importance of considering methodology in RCT interpretation. Review limitations include a small number of long-term studies and sample heterogeneity.
SIGNIFICANCE: This systematic review directly quantifies placebo effects from physical and psychological 'sham' control interventions and compares them to treatments' overall effectiveness. By doing so, the review enhances our understanding of placebo effects, their relative contribution in clinical trials, and their susceptibly to trial design. It poses further questions regarding the influence of blinding, participant expectations, and features of the therapeutic context. Overall, the insights provided by this review carry methodological significance and are important for the interpretation and synthesis of efficacy trials in this field.
related content
- “Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment,” Hróbjartsson et al, J Intern Med, 2004.
This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:
- Placebo analgesia in physical and psychological interventions: Systematic review and meta-analysis of three-armed trials. Hohenschurz-Schmidt 2024 Eur J Pain.
- Recovery trajectories in common musculoskeletal complaints by diagnosis contra prognostic phenotypes. Aasdahl 2021 BMC Musculoskelet Disord.
- Cannabidiol (CBD) products for pain: ineffective, expensive, and with potential harms. Moore 2023 J Pain.
- Moderators of the effect of therapeutic exercise for knee and hip osteoarthritis: a systematic review and individual participant data meta-analysis. Holden 2023 The Lancet Rheumatology.
- Inciting events associated with lumbar disc herniation. Suri 2010 Spine J.