Sham device v inert pill: randomised controlled trial of two placebo treatments. BMJ

Harvard University, Cambridge, Massachusetts, United States
BMJ (online) (Impact Factor: 17.45). 02/2006; 332(7538):391-7. DOI: 10.1136/bmj.38726.603310.55
Source: PubMed


To investigate whether a sham device (a validated sham acupuncture needle) has a greater placebo effect than an inert pill in patients with persistent arm pain.
A single blind randomised controlled trial created from the two week placebo run-in periods for two nested trials that compared acupuncture and amitriptyline with their respective placebo controls. Comparison of participants who remained on placebo continued beyond the run-in period to the end of the study.
Academic medical centre.
270 adults with arm pain due to repetitive use that had lasted at least three months despite treatment and who scored > or =3 on a 10 point pain scale.
Acupuncture with sham device twice a week for six weeks or placebo pill once a day for eight weeks.
Arm pain measured on a 10 point pain scale. Secondary outcomes were symptoms measured by the Levine symptom severity scale, function measured by Pransky's upper extremity function scale, and grip strength.
Pain decreased during the two week placebo run-in period in both the sham device and placebo pill groups, but changes were not different between the groups (-0.14, 95% confidence interval -0.52 to 0.25, P = 0.49). Changes in severity scores for arm symptoms and grip strength were similar between groups, but arm function improved more in the placebo pill group (2.0, 0.06 to 3.92, P = 0.04). Longitudinal regression analyses that followed participants throughout the treatment period showed significantly greater downward slopes per week on the 10 point arm pain scale in the sham device group than in the placebo pill group (-0.33 (-0.40 to -0.26) v -0.15 (-0.21 to -0.09), P = 0.0001) and on the symptom severity scale (-0.07 (-0.09 to -0.05) v -0.05 (-0.06 to -0.03), P = 0.02). Differences were not significant, however, on the function scale or for grip strength. Reported adverse effects were different in the two groups.
The sham device had greater effects than the placebo pill on self reported pain and severity of symptoms over the entire course of treatment but not during the two week placebo run in. Placebo effects seem to be malleable and depend on the behaviours embedded in medical rituals.

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    • "Another limitation was the inability to separate specific versus non-specific placebo effects of the acupuncture treatment. Clearly, there is a strong placebo component of acupuncture [34-36], and future sham-controlled trials are needed to parse-out various treatment elements. With this trial design, we cannot rule out the possibility of a placebo effect; however, participants had persistent PN in spite of having had previous treatment using standard of care methods, with which there would also have been expected benefit due to placebo. "
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    ABSTRACT: BackgroundThis single-arm study evaluated feasibility, safety, and initial efficacy of electroacupuncture for thalidomide/bortezomib-induced peripheral neuropathy (PN) in cancer patients with multiple myeloma.MethodsPatients with neuropathy ≥ grade 2 received 20 acupuncture treatments over 9 weeks.ResultsFor the 19 evaluable patients, Functional Assessment of Cancer Therapy/Gynecological Oncology Group-Neurotoxicity (FACT/GOG/NTX) mean (SD) scores improved significantly between baseline and week 13 (20.8 [9.6] vs 13.2 [8.5], p = 0.0002). Moderate effect size differences began on week 4, with the largest effect size differences found at week 9 for FACT/GOG/NTX scores, worst pain in the last 24 hours, and pain severity (Cohen’s d = 1.43, 1.19, and 1.08, respectively) and continuing through week 13 (Cohen’s d = 0.86, 0.88, and 0.90, respectively). From baseline to week 13, additional significant improvements were seen as follows: postural stability (1.0 [0.6] vs 0.8 [0.4], p = 0.02); coin test (10.0 [7.4] vs 5.6 [1.9], p < 0.0001); button test (96.1 [144.4] vs 54.9 [47.3], p < 0.0001); and walking test (21.6 [10.0] vs 17.2 [7.7], p = 0.0003). No significant changes were seen with NCS.ConclusionsAcupuncture may help patients experiencing thalidomide- or bortezomib-induced PN. Larger, randomized, clinical trials are needed.Trial Identifier: NCT00891618.
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    • "A wealth of research indicates that placebo effects can ameliorate both experimental [5,7,12,13,15,16,22,34,36,38,41–44] and clinical pain [26] [32] [40]. Recent neuroimaging studies demonstrate that placebo analgesia is accompanied by modulation of brain activity in regions known to process pain [8] [44]. "
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    ABSTRACT: Numerous studies indicate that placebo analgesia can be established via conditioning procedures. However, these studies have exclusively involved conditioning under continuous reinforcement. Thus, it is currently unknown whether placebo analgesia can be established under partial reinforcement and how durable any such effect would be. We tested this possibility using electro-cutaneous pain in healthy volunteers. Sixty undergraduates received placebo treatment (activation of a sham electrode) under the guise of an analgesic trial. The participants were randomly allocated to different conditioning schedules, namely continuous reinforcement (CRF), partial reinforcement (PRF), or control (no conditioning). Conditioning was achieved by surreptitiously reducing pain intensity during training when the placebo was activated compared with when it was inactive. For the CRF group, the placebo was always followed by a surreptitious reduction in pain during training. For the PRF group, the placebo was followed by a reduction in pain stimulation on 62.5% of trials only. In the test phase, pain stimulation was equivalent across placebo and no placebo trials. Both continuous and partial reinforcement produced placebo analgesia, with the magnitude of initial analgesia being larger following continuous reinforcement. However, while the placebo analgesia established under continuous reinforcement extinguished during test phase, the placebo analgesia established under partial reinforcement did not. These findings indicate that partial reinforcement can induce placebo analgesia and that these effects are more resistant to extinction than those established via continuous reinforcement. Partial reinforcement may, therefore, reflect a novel way of enhancing clinical outcomes via the placebo effect.
    Pain 03/2014; 155(6). DOI:10.1016/j.pain.2014.02.022 · 5.21 Impact Factor
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    • "In a previous clinical trial [5] of chronic pain patients, we found that sham acupuncture reduced pain significantly more over time than did placebo pills, while placebo pills offered more short-term benefits of improving pain-disturbed sleep over sham acupuncture. Thus it showed that not all placebo treatments are equal. "
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    ABSTRACT: Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol), sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for "placebo responders." However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non-specific effects of acupuncture may contribute to the analgesic effect observed in genuine acupuncture analgesia.
    PLoS ONE 07/2013; 8(7):e67485. DOI:10.1371/journal.pone.0067485 · 3.23 Impact Factor
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