In this controlled, crossover design study, we investigated several factors relevant to the mechanisms underlying the possible positive benefits of acupuncture in CLBP, such as placebo response, the impact of the level of psychopathology, and expectations for improvement. Overall, contrary to our hypothesis, both groups of CLBP patients, those with a High or Low level of psychopathology, benefitted similarly with either acupuncture or placebo treatment. Although, there was a trend for the High psychopathology group to experience less placebo analgesia than the Low group (17 vs. 34%, p=.09) The magnitude of response for the verum condition (an average 32.6% for both groups) mirrors the clinical improvement reported in the acupuncture RCTS for CLBP. We chose subjects with a discogenic component to their back pain because this is a very common presentation of CLBP, for which patients seek acupuncture treatment. In addition, we were most interested in understanding how psychiatric factors impact the response to a treatment for underlying physical pathology.
In our study, the benefits of verum
or placebo treatment were reported immediately after a session, and no ordering effects were seen. While the acupuncture treatment in this study was not a typical acupuncture treatment session for CLBP, our findings suggest that broad swaths of patients with CLBP may benefit, if only for its placebo effects. Interestingly, subjects rated the needling sensations during the verum
treatment as being fundamentally different than the placebo treatment. This result is in contrast to earlier studies that found the Streitberger placebo needle was rated more similarly to real acupuncture.61
It is unclear why this occurred, but it is possible that the manner in which the placebo needle was described and introduced in this study was different than earlier experiments. And yet, despite the subjects’ experiences of acupuncture differing from placebo in this study, both treatment sessions were analgesic. As noted, the complexity of the placebo phenomena makes it impossible to control for all nonspecific treatment effects. Such effects that were common to both sessions are the focused and caring attention of the healer on the patient, and the effects of relaxation during the treatment sessions.
Clinically, there are many subgroups of patients with CLBP and these results indicate that the level of psychopathology is not a determining factor in the response to acupuncture needling. The acupuncturist was blinded to group assignment and there was no evidence to suggest that the acupuncturist interacted differently with subjects from either group, which one could argue is a potential confound. Given the significant analgesia with verum or placebo needling at sites not commonly used in CLBP treatment, our results also raise the question of whether the specificity of needling sites is important to the therapeutic benefits of acupuncture.
As noted, in some studies positive expectations for relief have shown a positive correlation to acupuncture benefit,4, 31
but this is not universally the case.45
Previous studies in our group have shown that expectancy can be manipulated to augment the effectiveness of acupuncture,32
but these were performed in healthy normals with low levels of psychopathology at study entry. To our knowledge, no investigation studying the impact of expectations on acupuncture treatment for pain has examined whether comorbid psychiatric illness is a factor modulating the effect of expectations on acupuncture response for pain.33
Our findings indicate that greater expectations for improvement are a significant predictor of verum
acupuncture response, regardless of the level of psychopathology (as predicted). But, we did not find that the level of expectations significantly predicted the response to placebo acupuncture. This result must be interpreted cautiously, for the study was only adequately powered for a definitive analysis of the primary outcome. It is unclear why expectations significantly interacted with treatment and group in the verum
condition, but not the placebo condition. However, scores on the MASS scale indicate that the somatic experience of real acupuncture is fundamentally different than placebo, and perhaps there is some unknown relationship between these perceptions and the impact of expectations on verum
or placebo response.
Randomization order effects did not impact this finding, which suggests that when subjects in either group thought they were going to get acupuncture, they expected more relief and received it. The effectiveness of the blind does not appear to be a confounder since only 50% of subjects overall guessed correctly that they were receiving placebo treatment during that session. A 50% rate means that the ability of the subjects to guess the placebo treatment correctly is no better than chance alone. Hence, we can conclude that the placebo used in this study was credible. However, the High psychopathology group was more attune to receiving placebo for unclear reasons. The High group had an 18% greater rate of correct guessing and 50% less analgesia in the placebo condition compared to the Low psych group, which were nonsignificant differences. Overall, our findings indicate that the level of psychopathology does not significantly affect the analgesic benefits of acupuncture or placebo needling in CLBP and does not affect the positive impact of expectations on heightening acupuncture analgesia. Importantly, potential confounders, such as the degree of neuropathic pain or the level of physical disability, do not mitigate these results. Since our primary finding is contrary to our hypothesis, which was based on earlier studies using different treatments for CLBP, these results also suggest that the effects of psychopathology on treatment outcome are modality specific, and that the effect of expectations on outcome may depend on whether the treatment is real or placebo. That is, these factors may have different relationships to outcome depending on the treatment administered. Since psychiatric comorbidity bodes poorly for pain treatment outcome in general,7
this statement may not hold true depending on the type of treatment administered, particularly if the treatment in question has a strong mind-body emphasis, such as acupuncture. Future studies of acupuncture and placebo may consider an assessment for psychopathology in addition to expectancy effects, so that these relationships can be further investigated.
Since there were no significant relationships between analgesia during the verum
and placebo sessions, and no significant predictors of response to either treatment (except for expectations predicting verum
response only), our results add to the body of literature arguing that there are no valid means at present to identify placebo responders, be it to acupuncture or other treatments for pain.28, 42
These conclusions have implications for how analgesic effects are calculated in general, and for the conduct of acupuncture trials, more specifically. Our findings suggest that to determine the “true” or intrinsic analgesic properties of a treatment that subtracting placebo analgesia from the verum
treatment analgesia is not scientifically valid. And yet, this is quite a natural instinct whenever one sees a table or graph of treatment and placebo responses side by side. In terms of acupuncture, the high placebo responses seen in the RCTs may not signal that positive verum
acupuncture treatment results are just placebo effects. Indeed, a neurobiological basis for this interpretation is emerging. Recent brain neuroimaging findings from our group have demonstrated that as seen on fMRI, the evoked neural activation patterns are overlapping but distinctly different between verum
acupuncture analgesia and placebo acupuncture analgesia, even when controlling for the effects of expectancy.32
Several limitations of our study deserve discussion. First, the verum treatment we administered was not a commonly used treatment protocol for CLBP, and so our findings may not be wholly applicable to acupuncture treatment for CLBP. Therefore, our study adds no information on whether a typical acupuncture protocol has efficacy beyond placebo. However, since patients still significantly benefitted with this intervention to the same extent as they have in the RCTs for CLBP, our results do have implications for all forms of CLBP acupuncture treatment. Second, this was a study of acupuncture needling, and not a course of acupuncture treatment. We only examined immediate treatment response and not sustained benefit. And lastly, while our study was adequately powered for analysis of the primary pain outcome, it was not sufficiently powered for a definitive analysis of the covariates which can be said to apply to populations receiving acupuncture treatment for CLBP. Nevertheless, we can conclude with caution that within this sample of patients expectations for improvement do predict the response to verum acupuncture needling, but not placebo needling. Moreover, we can also conclude that within our sample no other covariates we examined were significantly relevant. These findings can inform the development of future studies.
In sum, the controlled and blinded study design provided a framework for a detailed analysis of the effects of placebo, psychopathology, and expectations on the response to acupuncture needling in patients with CLBP. Our findings reveal that the level of psychiatric comorbidity was not a significant predictor of verum or placebo responses, and that both treatments produced clinically meaningful analgesia. Expectations for improvement may only be a significant predictor of response to verum treatment, and this result may hold true regardless of the level of psychopathology.
Psychiatric comorbidity may predict differences between acupuncture and placebo responses, not otherwise seen in the RCTs for low back pain. Using a blinded, crossover design, we report that it does not predict outcome, nor does it seem to modify the effect of expectancy (a known, predictor) on acupuncture response.