Open-Label Placebo Trial among Japanese Patients with Chronic Low Back Pain

Abstract

Background. The aim of this study was to confirm the effectiveness of open-label placebo (OLP) in Japanese patients with chronic low back pain (CLBP), similar to previous reports, and to investigate its short- and medium-term effects in this study population. Methods. Fifty-two patients with CLBP were randomized into a treatment as usual (TAU) group (n = 26) or an OLP + TAU group (n = 26) for 12 weeks. The TAU included advice to remain active and exercise in conjunction with recent psychological education based on a self-management strategy. In contrast, participants in the OLP + TAU group were instructed to take two OLP capsules a day. Outcome measures were assessed at baseline and at weeks 3 and 12 using the Roland–Morris Disability Questionnaire (RMDQ), Numerical Rating Scale (NRS) for pain intensity, and the Timed-Up-and-Go (TUG) test. Difference in outcomes between the two groups was compared at the two follow-up points. Results. Although all participants completed the 3-week follow-up, four patients (two in each group) were lost to follow-up beyond week 3. There were no significant intergroup differences in changes in the RMDQ score ( p = 0.40 ), pain-NRS score ( p = 0.19 ), and TUG time ( p = 0.98 ) at week 3. Two-way repeated measure analyses of covariance showed significant time-course effects but did not show group effects or any interactions between the time-course and group in terms of the RMDQ score. However, it did not show any effects in the pain-NRS score and TUG time at week 12. Conclusions. The OLP + TAU group showed no superior findings in comparison with the TAU group after 3 weeks and 12 weeks for Japanese patients with CLBP. Nonetheless, significant improvements in functional disability were observed in both groups.

Placebo effects in low back pain: A systematic review and meta‐analysis of the literature

“…Fourteen clinical studies aimed at investigating patients with chronic LBP with averages in duration of pain ranging from 4.4 to 15.0 years (Borges et al., 2014 ; Brinkhaus et al., 2006 ; Bush et al., 1985 ; Carvalho et al., 2016 ; Charron et al., 2006 ; Cherkin et al., 2009 ; Degenhardt et al., 2014 ; Eardley et al., 2013 ; Ikemoto et al., 2020 ; Kim et al., 2020 ; Klinger et al., 2017 ; Leibing et al., 2002 ; Pach et al., 2011 ; Pires et al., 2020 ). Of these, 10 were clinical treatment studies comparing placebo interventions to a no‐treatment control (Borges et al., 2014 ; Brinkhaus et al., 2006 ; Bush et al., 1985 ; Cherkin et al., 2009 ; Degenhardt et al., 2014 ; Eardley et al., 2013 ; Kim et al., 2020 ; Leibing et al., 2002 ; Pach et al., 2011 ; Pires et al., 2020 ) and 4 were experimental studies specifically assessing placebo effects (Carvalho et al., 2016 ; Charron et al., 2006 ; Ikemoto et al., 2020 ; Klinger et al., 2017 ). Three clinical treatment studies investigated patients with acute LBP with a duration of less than 3 weeks (Faas et al., 1993 ; Sanders et al., 1990 ; Vas et al., 2012 ), and one study explored patients with subacute and chronic LBP (Bialosky et al., 2014 ).…”

“…Sham oral medication was administered in 3 out of 18 studies (Carvalho et al., 2016 ; Ikemoto et al., 2020 ; Klinger et al., 2017 ). In 2 studies, sham pills were used to investigate the effect of open‐label placebo's (Carvalho et al., 2016 ; Ikemoto et al., 2020 ).…”

“…Sham oral medication was administered in 3 out of 18 studies (Carvalho et al., 2016 ; Ikemoto et al., 2020 ; Klinger et al., 2017 ). In 2 studies, sham pills were used to investigate the effect of open‐label placebo's (Carvalho et al., 2016 ; Ikemoto et al., 2020 ). The pills were administered along with the instruction that they were inert yet could lead to functional improvement as a consequence of placebo effects.…”

“…One study showed a significant effect (p <.001) favouring placebo over no-treatment with an effect size of g = 0.74 (Carvalho et al, 2016). The other study did not report a significant effect (p = .40) (Ikemoto et al, 2020). The third study investigating LBP-related disability showed raw data for the placebo and no-treatment groups.…”

Can the Open Label Placebo Rationale Be Optimized?

“…As shown in Table 1, this 4-point discussion has become standard across OLP trials in clinical populations. With few exceptions (7,8), all studies that examined the efficacy of OLPs outside a dose-extension model have used a rationale almost identical to or a close variation of that used in the Kaptchuk et al study (9)(10)(11)(12)(13)(14)(15)(16)(17). Regarding the exceptions, patients in Kleine-Borgmann et al (7) simply watched a video describing OLPs and those in Nitzan et al (8) were told about past efficacy of placebos in studies and that they would likely help alleviate some depressive symptoms.…”