Can the Nocebo Effect in Pain Management Be Reduced by Patient Education?

After reading a description of the nocebo concept in an online survey, approximately one-third of a general population sample from Denmark and the United States stated they agreed that receiving information about side effects can increase their incidence, according to study results reported in the European Journal of Pain. The findings have implications for implementation of nocebo education and risk-framing strategies.

The term nocebo describes negative effects of a treatment caused by a patient’s expectations or beliefs. Nocebo effects may include worsened symptoms, less effective treatment, or adverse side effects, and their impact on the perception of pain is substantial. However, nocebo effects can be minimized through patient education, nondisclosure (with the patient’s consent), positive framing, and tailored information.

To guide design and execution of nocebo effect-minimization strategies in pain management, health care user perspectives are essential. To better understand beliefs and attitudes about nocebo effects, researchers conducted a cross-sectional study comprising a large-scale online survey of general population samples in Denmark and the United States. Study methodology followed the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines.

During the survey, which was conducted in Danish and English, 2766 adults (1397 in the Danish sample and 1369 in the US sample) provided a complete response to questions about their familiarity with nocebo effects, their beliefs about these effects, and their attitudes toward disclosure of side effects. Among the survey respondents, mean age was 47 years (range, 18 to 99 years) and 58% were women. In the US sample, 66.6% of respondents self-reported as White; race/ethnicity information was not available for the Danish sample. Slightly more than half (58%) had at least 1 chronic disease, and 15% had chronic pain. The majority (67%) of the cohort reported taking or having taken medication, and 66% had undergone surgery.

Participants were first asked to respond to 2 questions that assessed their familiarity with the terms nocebo and nocebo effect and the concept of nocebo side effects. Subsequently they were provided with a brief description of side effects, nocebo side effects, and moral issues faced by clinicians regarding full disclosure of potential treatment side effects during the process of informed consent vs patient experience of nocebo side effects related to this disclosure. These descriptions were followed by survey questions that assessed attitudes towards side effect disclosure and positive framing as a means of presenting side effect information in a manner that would minimize nocebo side effects. Finally, participants were asked a series of questions regarding to what extent they agreed that receiving information about side effects could increase their incidence.

Spearman’s rho and point-biserial correlations were used to test for associations between knowledge about nocebo side effects and attitudes towards side effect information. A correlation coefficient of 0.10 or greater was considered meaningful. General linear models were used to analyze sample differences in attitudes towards side effect disclosure.

Survey responses indicated that while 17% of all participants were familiar with the term nocebo, 50% were familiar with the concept with respect to side effects. A total of 31% of participants agreed or completely agreed that providing information about side effects could increase their incidence, 39% agreed somewhat, and 30% disagreed.

Greater belief in the nocebo effect was associated with more negative attitudes toward side effect disclosure. However, 73% of participants overall (73.3% of Danes and 73.5% of US respondents) believed using positive framing to provide side effect information was acceptable, and only 10% disagreed with use of positive framing.

The majority of participants (65.1% overall; 55.3% of the Danish group vs 75.1% of the US group) favored disclosing all possible side effects. A greater majority of participants, 83.6%, favored ensuring that a patient is fully informed about potential side effects of a treatment. Only 16.4% prioritized having their clinician withhold side effect information to avoid increasing their risk of experiencing side effects.

Most participants, 84.3%, considered having a clinician present no information about the side effects of a pain treatment to be irresponsible. In contrast, only 1.8%, stated that they preferred not to receive any information about side effects.

Information about severe and frequent side effects was considered important by approximately 89% of survey respondents overall, information about mild side effects was considered important by 69.0%, and information about rare side effects was considered important by 52.3%. In the overall cohort, 42.1% of participants (30.8% in the US sample vs 54.1% in the Danish sample) agreed that a patient’s health care provider should decide what information to disclose and considered this approach to be responsible.

Compared with survey respondents who had no chronic pain, those with chronic pain were significantly more likely to agree that a clinician should disclose all side effects, even mild ones. They were also significantly less likely to agree to let clinicians choose which information to disclose.

Compared with Danes, US participants had greater familiarity with and belief in the nocebo effect and a stronger preference for  disclosure of side effects. US participants were also less likely than Danes to agree to let clinicians choose which information to disclose.

Limitations of this study include differences in participant recruitment and compensation between Denmark vs the United States, which may explain differences in the response rates. Additionally,, use of a general population sample limited the level of detail available regarding participants’ chronic pain type and duration, as well as the effects of these variables on quality of life.

The investigators concluded, “Nocebo belief was low yet consistently associated with more lenient attitudes towards side effect disclosure.”  They added, “Furthermore, the study uncovered a gap between nocebo familiarity and nocebo belief, as well as positive attitudes towards the use of framing. With large nocebo effects in pain and new indications that side effect information is especially important to people living with pain, the study provides important insight to the medical and ethical discussion about the management of nocebo side effects.”

This article originally appeared on Clinical Pain Advisor