PainRelief.com: What are the main findings?
Response: Compared head-to-head in a randomized double-blind protocol, there was no evidence of greater reduction in either pain intensity (Differential Description Scale) or pain disability (Roland Morris Disability Questionnaire) between any of the four treatments groups.
The four treatments groups consisted of:
1) Desipramine Hydrochloride;
2) Desipramine & Cognitive Behavioral Therapy;
3) Cognitive Behavioral Therapy & Active Placebo (Benztropine Mesylate); and
4) Active Placebo alone.
Instead, all groups showed statistically significant pre-to-posttreatment reductions on both primary outcome measures. To address the concern that group similarities reflected deficiencies in statistical power, we also examined effect sizes and rates of clinically significant changes (>30% reductions in pain intensity or disability). These analyses yielded the same conclusion: We observed moderate to large effect size changes in each group (~.5-.8 in Cohen’s d values), and 33.3%-47% rates of clinically significant symptom decreases.
There are several methodological features that are important to consider in interpreting this finding.
a) First, we used a rigorous inclusion/exclusion protocol to reduce potential confounds. These exclusions made our sample different from many of the chronic back pain patients seen by pain providers in routine practice. For example, we required daily pain symptoms of an intensity 4 or greater/10. We similarly excluded patients with significant mental health conditions, including major depression.
b) Secondly, we employed a biologically active placebo (Benztropine Mesylate) whose side effects mirrored those of our active medication treatment, Desipramine. The objective of this step was to blind participants as much as possible to their treatment, knowing that this could also increase the magnitude of the placebo effect.
c) Thirdly and related to b) we used genetic testing to phenotype patients and adjust their Desipramine schedules and achieve serum concentration levels in established therapeutic dose ranges. Thus, participants did not receive a standardized Desipramine dose; based on their phenotype results, participant’s starting doses and titration schedules differed. However, this step ensured that participants receiving Desipramine were receiving clinically effective doses.
PainRelief.com: What should readers take away from your report?
1) Although the number of previous trials comparing pain medicines and cognitive behavioral therapies to active controls is small, our results are consistent with this literature. Under controlled conditions, previous trials suggest that differences between active treatments and active controls are usually non-significant. Thus, the placebo effect remains alive and well as a potentially viable alternative treatment for chronic back pain based on our results.
2) Notably, we can’t say that the effects would have been the same with a “sugar pill” (biologically inactive placebo) instead of the Benztropine Mesylate. We also can’t discount that there was also a placebo effect contributing to the Desipramine and Cognitive Behavioral Therapy treatments as well; it is plausible that beliefs about pain treatment explain a substantial portion of medical and psychological treatments, a position paralleled by statements from the Institute of Medicine in describing the reliable benefits of placebo effects in pain treatments.
PainRelief.com: What recommendations do you have for future research as a result of this work?
Response: Beyond our primary questions about the overall efficacy of the treatments and between group treatment differences, we hope to understand more about the variation in participants’ responses. As noted, between a third and half of the participants showed clinically significant reductions in pain intensity or pain disability. Treatment assignment did not predict participant effects. Our current analyses are examining medical, demographic, and psychological factors that may help identify participants more likely to experience larger treatment effects or larger responses to active placebo conditions. For us, these are exploratory questions that may offer clues to evaluate in subsequent studies.
A randomized placebo-controlled trial of desipramine, cognitive behavioral therapy, and active placebo therapy for low back pain.
Gould HM, Atkinson HJ, Chircop-Rollick T, D’Andrea J, Garfin S, Patel SM, Funk SD, Capparelli EV, Penzien DB, Wallace M, Weickgenant AL, Slater M, Rutledge T
Pain. 2020 Feb 12. PMID: 32068667
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