Effectiveness of Placebo Interventions for Patients With Nonspecific Low Back Pain

A Systematic Review and Meta-analysis

Rob H.W. Strijkers; Marco Schreijenberg; Heike Gerger; Bart W. Koes; Alessandro Chiarotto

Pain. 2021;162(12):2792-2804.

Conclusion

Placebo interventions in any form seem to be mildly effective in reducing pain intensity in patients with chronic nonspecific LBP at short-term follow-up compared with no intervention. The reduction in pain intensity of 8 points on a 0 to 100 pain scale was statistically significant but may be of limited clinical relevance. Results are independent of the actual type of placebo intervention. A small difference was seen in physical functioning outcome between placebo and no intervention, but this difference may also not be clinically relevant. Placebo intervention improved the physical summary component score of the Short-Form 36 compared with no intervention.

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Acknowledgements
The authors would like to thank Wichor M. Bramer for his help in developing the database search syntaxes for this systematic review.
M. Schreijenberg, A. Chiarotto, and B.W. Koes made substantial intellectual contributions to the development of the original study protocol of this systematic review. R.H.W. Strijkers and M. Schreijenberg performed the data selection, data extraction, and risk of bias assessment. R.H.W. Strijkers conducted the analyses under supervision of H. Gerger and A. Chiarotto. R.H.W. Strijkers, A. Chiarotto, and H. Gerger interpreted the results. R.H.W. Strijkers and M. Schreijenberg drafted the manuscript, which was revised by A. Chiarotto, B.W. Koes, and H. Gerger. All authors have read and approved the final manuscript.

Table 1. Characteristics of eligible studies (n = 21).
First author, journal, year of publication	Population total sample participants (N) mean age in y (SD)	Percentage female participants	Duration of complaints acute (<6 wk), subacute (6–12 wk), or chronic (>12 wk)	Placebo intervention group	Comparison control group	No. of treatments. Total duration of treatment.	Pain outcome measures	Physical functioning outcome measures	Quality of life outcome measures	Follow-up available
Bialosky et al.,² 2014	Placebo N = 27 Age placebo: 33.22 (13.29) Control N = 27 Age control: 29.85 (12.09)	Placebo 63% Control 68%	Chronic	Placebo spinal manipulative therapy	No intervention	N = 6 2 wk	NRS	ODI	NA	2 wk
Borges et al.,⁴ 2014	Placebo N = 15 Age: 39.6 (9.6)* Control N = 14 Age: 39.6 (9.6)*	Placebo 73.3% Control 64.3%	Chronic	Sham laser therapy	No intervention	N = 12 6 wk	NRS	NA	NA	6 wk
Brinkhaus et al.,⁵ 2006	Placebo N = 70 Age placebo: 58.2 (9.4) Control N = 74 Age control: 58.9 (9.5)	Placebo 75.3% Control 68.4%	Chronic	Sham acupuncture	Waiting list	N = 12 8 wk	VAS pain	FFbH-R	SF-36, MCS, and PCS	8 wk
Carvalho et al.,⁶ 2016	Placebo N = 41 Age placebo: 44.4 (13.2) Control N = 42 Age control: 44.1 (13.7)	Placebo 70.7% Control 71.4%	Chronic	Open-label placebo pills	Treatment as usual	N = 2dd2 3 wk	NRS	RMDQ	NA	3 wk
Celenay et al.,⁷ 2019	Placebo N = 21 Median (range) Age placebo: 48 (39–63) Control N = 21 Median(Range) Age control: 55 (24–65)	Placebo 81% Control 71%	Chronic	Sham massage therapy	Standard treatment	N = 15 3 wk	VAS pain	ODI	SF-36, MCS, and PCS	3 wk
Eardley et al.,¹⁴ 2013	Placebo N = 21 Age placebo: 48.1 (10.6) Control N = 17 Age control: 44.6 (10.3)	Placebo 67% Control 64.7%	Chronic	Sham physiotherapy	Waiting list	N = 5 5 wk	VAS pain	RMDQ	SF-36, MCS, and PCS	5 wk
Farasyn et al.,¹⁶ 2006	Placebo N = 20 Age placebo: 43 (12) Control N = 20 Age control: 40 (12)	Placebo 55% Control 56%	Sub-acute	Sham endermology treatment	Waiting list	N = 1 30 min	VAS pain	ODI	NA	1 wk
Imamura et al.,³⁵ 2016	Placebo N = 125 Age placebo: 47.91 (8.52) Control N = 127 Age control: 48.01 (9.48	Placebo 70.4% Control 63.78%	Chronic	Sham infusion therapy	Standard treatment	N = 3 3 wk	VAS pain	RMDQ	NA	3 mo
Kleine-Borgmann et al.,³⁷ 2019	Placebo N = 67 Age placebo: 60.2 (15.15) Control N = 60 Age control: 58.37 (13.97)	Placebo 55.6% Control 69.5%	Chronic	Open-label placebo pills	Treatment as usual	N = 21 21 d	NRS	ODI	NA	3 wk
Köroglu et al.,³⁸ 2017	Placebo N = 20 Age placebo: 50.3 (11.5) Control N = 20 Age control: 47.9 (15.2)	Placebo 60% Control 40%	Chronic	Placebo taping	Treatment as usual	N = 10 2 wk	VAS pain	ODI	NA	4 wk
Leichtfried et al.,³⁹ 2014	Placebo N = 36 Median (range) Age placebo: 47 (39–54) Control N = 33 Median (range) Age control: 52.5 (49–58)	Placebo 58% Control 57%	Chronic	Light intervention	Prestudy therapy	N = 9 3 wk	Brief Pain Inventory subscore 1	NA	NA	3 wk
Lewis et al.,⁴⁰ 2010	Placebo N = 28 Age: 39.2 (11.1)* Control N = 28 Age: 39.2 (11.1)*	NA	Mixed, mostly Chronic	Sham strain-counterstrain exercise	Laying in a sleeping position for 6 min	N = 1 6 min	VAS pain	NA	NA	1–3 d
Licciardone et al.,⁴¹ 2003	Placebo N = 23 Age placebo: 52 (12) Control N = 17 Age control: 49 (12)	Placebo 57% Control 65%	Chronic	Sham manipulation therapy	Received no intervention	N = 7 5 mo	VAS pain	NA	NA	1, 3 and 6 mo
Luz Jr et al.,⁴² 2015	Placebo N = 20 Age placebo: 50.1 (17.5) Control N = 20 Age control: 48.1 (13.4)	Placebo 65% Control 85%	Chronic	Sham taping	No intervention	N = 1 48 h	NRS	RMDQ	NA	1 wk
Marchand et al.,⁴³ 1993	Placebo N = 12 Age placebo: 35.08 (7.38) Control N = 16 Age control: 37.25 (8.18)	Placebo 50% Control 50%	Chronic	Sham tense therapy	Waiting list	N = 20 10 wk	VAS pain	NA	NA	3, 6 mo
Molsberger et al.,⁴⁵ 2002	Placebo N = 61 Age placebo: 50 (6) Control N = 60 Age control: 49 (7)	Placebo 45.90% Control 53.33%	Chronic	Sham acupuncture	Standard therapy	N = 12 4 wk	VAS pain	NA	NA	3 mo
Moura et al.,⁴⁶ 2019	Placebo N = 36 Age placebo: 51.03 (14.9) Control N = 37 Age control: 46.19 (15.73)	Placebo 75% Control 81%	Chronic	Sham acupuncture	No orientation, no intervention.	N = 5 5 wk	Brief Pain Inventory	NA	NA	2 wk
Pach et al.,⁵⁰ 2011	Placebo N = 43 Age placebo: 54.8 (11.3) Control N = 50 Age control: 56.7 (10.7)	Placebo 56.3% Control 56.9%	Chronic	Sham injection	No treatment	N = 12 8 wk	VAS pain	FFbH-R	SF-36, MCS, and PCS	2, 6 mo
Schmitz et al.,⁵⁴ 2019	Placebo N = 21 Age placebo: 55.48 (10.72) Control N = 14 Age control: 48.07(8.49)	Placebo 76.19% Control 57.14%	Chronic	Sham transdermal infusion	No treatment	N = 2 8 d	NRS	FFbH-R	NA	8 d
Vas et al.,⁵⁸ 2012	Placebo N = 69 Age placebo: 43.6 (12.2) Control N = 70 Age control: 41.2 (12)	Placebo 49.3% Control 64.3%	Acute	Sham acupuncture	Treatment as usual	N = 5 2 wk	VAS pain	RMDQ	NA	3 wk
Wepner et al.,⁶² 2008	Placebo N = 18 Age: 47.06 (9.33)* Control N = 18 Age: 47.06 (9.33)*	NA	Chronic	Sham singing bowls therapy	Treatment as usual	N = 6 4 wk	VAS pain	RMDQ	SF-36, MCS, and PCS	5 wk

*Not separately available.
FFbH-r, Hannover Functional Ability Questionnaire; MCS, mental component summary; NRS, numerical rating scale; NA, not available; ODI, Oswestry Disability Index; PCS, physical component summary; RMDQ, Roland–Morris Disability Questionnaire; VAS, visual analog scale; SF-36, Short-Form 36.