Thursday, May 30, 2024

Placebo Response Strongest in Depression Trials, but Robust Across Multiple Psychiatric Disorders

In a meta-analysis published yesterday in JAMA Psychiatry, researchers found that people with major depression showed the strongest placebo response in clinical trials among nine psychiatric disorders assessed, followed by individuals with generalized anxiety disorder. However, the placebo response was significant across all nine disorders.

“A genuine placebo effect, by definition, encompasses improvements induced by suggestion, hope for effective treatment, and conditioning effects through the administration of medications,” wrote Tom Bschor, M.D., of the Technical University of Dresden, Germany, and colleagues. In the case of psychiatric illness, factors such as the episodic course of many disorders and the attentive and compassionate care that clinical trial participants often receive also influences the placebo response, they added.

“A better understanding of placebo responses may improve treatments, especially in psychiatric disorders where confidence, conditioning, and belief play a significant role,” the researchers wrote.

Bschor and colleagues assessed placebo response for nine psychiatric disorders commonly treated with medications: attention-deficit/hyperactivity disorder, generalized anxiety disorder, major depressive disorder, mania, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, schizophrenia, and social anxiety disorder.

For each disorder, they combined patient data from 10 high-quality placebo-controlled trials; their final sample included nearly 10,000 clinical trial participants who received placebo.

Overall, placebo group participants showed strong symptom improvements for all nine disorders assessed. The greatest placebo response was seen for major depression and generalized anxiety, which had effect sizes of 1.40 and 1.23, respectively. An effect size is a standardized value to quantify changes like symptom improvements; an effect size above 1.2 is considered a very large change. At the other end were patients with schizophrenia and obsessive-compulsive disorder, who had placebo response effect sizes of 0.59 and 0.65, respectively (medium-to-large changes).

“[P]atients with schizophrenia had the least benefit associated with placebo treatment, possibly due to episodic relapses and an unfavorable prognosis,” Bschor and colleagues wrote. “Impaired interpersonal functioning might reduce the impact of personal attention and nonspecific effects in placebo groups. Distorted reality perception and limited insight into illness may hinder the development of hope and belief in effective treatment.”

The researchers also found that females appeared to show a stronger placebo response than males on average, though this sex difference alone did not explain why the strongest effect sizes were found in the depression and anxiety clinical trials (whose participants were ~65% female). For example, 21% of the participants in the posttraumatic stress disorder trials were female, yet the effect size was still large (0.84).

For related information, thee the American Journal of Psychiatry article, “Patient Expectancy as a Mediator of Placebo Effects in Antidepressant Clinical Trials.”

(Image: Getty Images/iStock/Kudryavtsev Pavel)

Psychiatric News Seeks Contributions From Members

New Editor in Chief Adrian Preda, M.D., invites APA members to become involved in Psychiatric News by writing news or opinion articles on the topic of their choice or by applying for leadership positions to invite and curate articles from other members in new sections that include the areas of technology, sex and gender issues, advocacy, psychotherapy, integrated psychiatry and primary care, and consultation-liaison psychiatry. Interested? For more information, send an email to


The content of Psychiatric News does not necessarily reflect the views of APA or the editors. Unless so stated, neither Psychiatric News nor APA guarantees, warrants, or endorses information or advertising in this newspaper. Clinical opinions are not peer reviewed and thus should be independently verified.