Stimulated by Power et al 2020, and Kang et al 2020.
Placebo figured heavily in last week’s blog, so I could not overlook this paper when it appeared on PubMed at the end of the same week. The first author has a remarkably suitable name on a paper that tests whether or not the placebo effect is more or less powerful in chronic pain patients compared with healthy individuals.
Andrea Power and colleagues from Manchester, Liverpool and Leeds recruited 60 patients with osteoarthritis (OA), 79 with fibromyalgia (FM) and 98 healthy individuals (HI). They used an inert cream that was made to look like the application of a local anaesthetic cream, and a laser stimulus calibrated to each individual to reliably obtain a pain rating of 7 on a scale from 0 to 10. The laser was turned down to 3 out of 10 on one forearm to condition participants who were expecting to receive an anaesthetic cream on one side. This was also done in the control group who knew the cream was inactive on both sides.
There was no difference in the placebo response between patients in either group or healthy controls. The FM patients had higher levels of anxiety throughout, but placebo responses did not seem to be influenced by this, nor were they influenced by expectation. Also, curiously, there was both site specific and site non-specific placebo responses, although the expected (conditioned) site of analgesia did generate a greater placebo response.
The authors had quite a bit of discrepancy with prior research to explain, including the apparent lack of influence (correlation) of anxiety or expectation with the size of the placebo response. Expectation only correlated with response within the placebo group where overt manipulation of expectation was congruent with covert conditioning.
Another paper popped up the same day as Power et al, but on an entirely different topic. It is a topic we have discussed on this blog in the past: electroacupuncture (EA) in mixed urinary incontinence (MUI). MUI is a combination of stress urinary incontinence (SUI) and urge urinary incontinence (UUI), but often one or other of these predominates. This paper reanalysed the data from a large prior trial on MUI, and selected a subgroup of women with balanced MUI, which is apparently more resistant to treatment. The original trial randomised 500 women, and out of this group only 79 were found to have balanced MUI. 34 had been randomised to EA and 45 to conventional care with the drug solifenacin and pelvic floor muscle training (PFMT). When the results of this subgroup were analysed, 32% were responders in the EA group and 37% in the conventional care group. The wide confidence intervals meant that EA was considered non-inferior. Responders were determined by a 50% or greater reduction in 24-hour incontinence episode frequency (24-h IEF). The primary outcome used in the larger original trial was 72-h IEF, and for that outcome 38% were responders in the EA group, and 36% in the conventional care group. I am unsure why the difference in primary outcome, since the 72-h IEF would also have been available as it was in the original larger dataset, so I have written to the authors to ask.
Whilst I was seeking full text of the paper at the Int Urogunecol J website, I was scrolling through the online first publications in this journal, and another related paper caught my eye. This one was a retrospective cohort examining the long-term success rates of percutaneous tibial nerve stimulation (PTNS) maintenance therapy. 141 patients initiated monthly maintenance therapy after a course of 12 weekly sessions. This group derived from a cohort of 640 patients with overactive bladder (OAB) symptoms who had initiated PTNS in Southern California under Kaiser Permanente from January 2015 to August 2017. Of the original number (470 after 170 were excluded) 141 (30%) went on the monthly maintenance, 66 (14%) completed one year of treatment, and 60 (12.8%) were considered successful based on patient global impression of improvement (PGI-I) scores.
PTNS is EA in the leg, and MUI is of course somewhat worse than OAB, and of course the outcomes are entirely different, so we should not compare the results even in passing. The longest outcome we have from the MUI trial is 25–36 weeks, at which point the responder rate to EA and conventional care was over 70%.
1 Power A, Brown CA, Sivan M, et al. Individuals with chronic pain have the same response to placebo analgesia as healthy controls in terms of magnitude and reproducibility. Pain Published Online First: 24 June 2020. doi:10.1097/j.pain.0000000000001966
2 Kang J, Sun Y, Su T, et al. Electroacupuncture for balanced mixed urinary incontinence: secondary analysis of a randomized non-inferiority controlled trial. Int Urogynecol J 2020;38:1035–42. doi:10.1007/s00192-020-04305-5
3 Liu B, Liu Y, Qin Z, et al. Electroacupuncture Versus Pelvic Floor Muscle Training Plus Solifenacin for Women With Mixed Urinary Incontinence: A Randomized Noninferiority Trial. Mayo Clin Proc 2019;94:54–65. doi:10.1016/j.mayocp.2018.07.021
4 Jung CE, Menefee SA, Diwadkar GB. Percutaneous tibial nerve stimulation maintenance therapy for overactive bladder in women: long-term success rates and adherence. Int Urogynecol J Published Online First: 22 June 2020. doi:10.1007/s00192-020-04325-1