Pain
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The investigation of nocebo effects is evolving, and a few literature reviews have emerged, although so far without quantifying such effects. This meta-analysis investigated nocebo effects in pain. We searched the databases PubMed, EMBASE, Scopus, and the Cochrane Controlled Trial Register with the term "nocebo." Only studies that investigated nocebo effects as the effects that followed the administration of an inert treatment along with verbal suggestions of symptom worsening and that included a no-treatment control condition were eligible. ⋯ In studies in which nocebo effects were induced by a combination of verbal suggestions and conditioning, the effect size was larger (lowest g=0.76 [0.39-1.14] and highest g=1.17 [0.52-1.81]) than in studies in which nocebo effects were induced by verbal suggestions alone (lowest g=0.64 [-0.25 to 1.53] and highest g=0.87 [0.40-1.34]). These findings are similar to those in the placebo literature. As the magnitude of the nocebo effect is variable and sometimes large, this meta-analysis demonstrates the importance of minimizing nocebo effects in clinical practice.
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The degree of variability in the patient baseline 7-day diary of pain ratings has been hypothesized to have a potential effect on the assay sensitivity of randomized clinical trials of pain therapies. To address this issue, we obtained clinical trial data from the Food and Drug Administration (FDA) through the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership, and harmonized patient level data from 12 clinical trials (4 gabapentin and 8 pregabalin) in postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Models were developed using exploratory logistic regression to examine the interaction between available baseline factors and treatment (placebo vs active medication) in predicting patient response to therapy (ie, >30% improvement). ⋯ In addition, there was a small but significant age-by-treatment interaction in the PHN model, and small weight-by-treatment interaction in the DPN model. The patient's sex, baseline pain level, and the study protocol had an effect only on the likelihood of response overall. Our results suggest the possibility that, at least in some disease processes, excluding patients with a highly variable baseline 7-day diary has the potential to improve the assay sensitivity of these analgesic clinical trials, although reductions of external validity must be considered when increasing the homogeneity of the investigated sample.