No Clear Pattern for Predicting Nocebo Response in Bipolar Disorder

White oval pills
White oval pills
Investigators assessed patterns and predictors of nocebo events, which included worsening of clinical symptoms and/or treatment-emergent adverse events.

There is no clear pattern to identify patients who will have a nocebo response to treatment for bipolar disorder, according to results published in Bipolar Disorders.

The researchers analyzed 9 placebo-controlled randomized clinical trials of olanzapine for the treatment of bipolar disorder. They looked at data from placebo-treated participants in order to identify participant or study characteristics associated with a nocebo event. They defined a nocebo event as any treatment-emergent adverse event (TEAE) or increase in score from baseline to end point for primary measures of clinical symptoms.

Of 1185 participants randomly assigned to placebo, 68% (n=806) reported a TEAE. Only 649 participants treated with placebo had available Hamilton Depression Rating Scale (HDRS) data; of these, 49.5% (n=321) had worsening scores.

The results did indicate that some variables are associated with an increased likelihood of a nocebo response, including being treatment-naïve, younger age, and being classified as obese. The researchers found that nocebo events were associated with not being treatment-naïve, younger age, being located in the United States, being a participant in an earlier study, and being classified as obese.

Related Articles

“Further research is still needed to characterize the nocebo response,” the researchers wrote. “While sometimes envisaged as an uncommon response among[st] people susceptible to negative expectations, these data suggest that the nocebo response is more likely a common response that, similar to the placebo response, is an expected consequence of exposure to a therapeutic intervention.”


Dodd S, Walker AJ, Brnabic AJM, Hong N, Burns A, Berk M. Incidence and characteristics of the nocebo response from meta-analyses of the placebo arms of clinical trials of olanzapine for bipolar disorder [published online June 21, 2018]. Bipolar Disord. doi:10.1111/bdi.12662