Educating about nocebo effects helps improve tolerance to tricyclic antidepressants

A short intervention that addresses the nocebo (negative placebo) effect appears to improve tolerance of tricyclic antidepressants (TCAs), which are commonly used to treat disorders of gut-brain interaction (DGBI), a study has shown.

In this pilot randomized controlled trial in a tertiary care gastroenterology clinic, the investigators randomly assigned 31 patients with DGBI to either “standard information,” which described the benefits and risks of TCAs, or “augmented information,” which included an additional <30-second education about nocebo effects.

Two weeks after the first visit, participants received an online survey evaluating the number and “bothersomeness” of side effects, adequate relief, global improvement, and treatment satisfaction.

Of the participants, 22 responded to the survey (mean age 40 years, 59 percent women). The augmented group attributed nominally fewer symptoms to TCAs than did the standard group, albeit not statistically significant and with a medium effect size (1.5 vs 4.2; d, 0.56; p=0.212); the augmented group also reported being remarkably less bothered by these symptoms (13.4 vs 38.1; p=0.037).

In addition, a nominally larger proportion of patients in the augmented group reported adequate relief of symptoms after 2 weeks of treatment relative to those in the standard group (55 percent vs 27 percent, respectively).

“These findings provide support for future, fully powered studies to evaluate the impact of framing on clinical outcomes, especially in chronic conditions,” the investigators said.

TCAs are often associated with side effects that lead to early discontinuation. Previous studies suggest that many of these side effects may be caused by nocebo effects, according to the investigators.