How Strong is the Placebo Effect in Anxiety and Related Disorders?

What you need to know

• Placebo effects are large in clinical trials for anxiety, obsessive-compulsive, and stress-related disorders, with about 37% of patients improving on placebo alone.
• Placebo responses are strongest for generalized anxiety disorder and post-traumatic stress disorder.
• The strength of placebo effects does not differ significantly between children, adults, and older adults.
• Strong placebo responses make it challenging to determine the true benefits of anxiety medications in clinical trials.

Understanding the placebo effect in anxiety disorders

When researchers test new medications for anxiety and related disorders, they often compare the drug to a placebo - an inactive substance with no therapeutic value. This allows them to determine if the medication is truly effective beyond just the expectation of improvement. However, placebos themselves can have powerful effects, especially for mental health conditions.

This study aimed to measure how strong the placebo effect is in clinical trials for anxiety, obsessive-compulsive disorder (OCD), and stress-related disorders like post-traumatic stress disorder (PTSD). The researchers analyzed data from 135 clinical trials involving over 12,500 participants who received placebos instead of active medications.

A powerful placebo response

The analysis found that placebo effects were quite substantial across these disorders. On average, patients taking placebos showed large improvements in their symptoms, with an effect size of -1.11. In psychology research, an effect size of 0.8 or higher is considered large.

Looking at response rates, about 37% of patients taking placebos were classified as “responders,” meaning they had a significant reduction in symptoms. Additionally, 24% of placebo patients achieved “remission,” or a near-complete resolution of symptoms.

These high placebo response rates are important to consider when evaluating anxiety treatments. If over one-third of patients improve on placebo alone, it becomes more difficult to prove that a medication is truly effective beyond this placebo effect.

Differences between disorders

The strength of the placebo effect varied depending on the specific disorder:

• Generalized anxiety disorder (GAD) and PTSD showed the largest placebo responses
• Panic disorder, social anxiety disorder, and OCD had somewhat smaller placebo effects

This suggests that conditions like GAD and PTSD may be more susceptible to placebo effects, while disorders like OCD may be less influenced by placebo. Understanding these differences can help researchers design better clinical trials for each condition.

Age and placebo response

Interestingly, the study found no significant differences in placebo response between children, adults, and older adults. This contradicts some previous research suggesting that children might have stronger placebo responses for other conditions. For anxiety disorders, it appears the placebo effect is relatively consistent across age groups.

Factors influencing placebo response

The analysis identified a few factors that seemed to influence the strength of placebo effects:

• Using a placebo “lead-in” period reduced placebo response. This involves giving all participants placebo for a short time before the main trial to exclude those who respond quickly to placebo.
• For adults, allowing use of anti-anxiety medications like benzodiazepines alongside placebo increased placebo response.
• Trials comparing multiple active medications (rather than just medication vs. placebo) saw higher placebo responses in adults.

Implications for treatment and research

These findings have important implications for both treating anxiety disorders and conducting research on new treatments:

For patients and clinicians:

• A significant portion of symptom improvement from anxiety medications may be due to placebo effects rather than the drug itself.
• Factors like positive expectations and increased attention from healthcare providers likely contribute to symptom improvement, even with inactive treatments.
• Non-drug approaches that harness these “active ingredients” of the placebo effect may be beneficial.

For researchers:

• Clinical trials need to account for large placebo responses when testing new anxiety medications.
• Strategies like placebo lead-in periods may help isolate true drug effects.
• Comparing a new drug to existing medications (rather than just placebo) may provide more meaningful results.

Limitations to consider

While this analysis provides valuable insights, there are some limitations to keep in mind:

• There was high variability between studies, suggesting other unmeasured factors influence placebo response.
• Smaller studies tended to show different results than larger ones, which could bias the overall estimates.
• The study looked at changes from the start to end of trials, so can’t account for natural symptom fluctuations over time.

Conclusions

• Placebo effects are powerful in clinical trials for anxiety, OCD, and stress-related disorders, with over one-third of placebo patients showing significant improvement.
• The strength of placebo response varies between disorders, being strongest for generalized anxiety and PTSD.
• Age does not appear to significantly influence placebo response for these conditions.
• Strong placebo effects make it challenging to prove the true benefits of anxiety medications beyond expectation effects.
• Both clinicians and researchers need to consider the substantial role of placebo when evaluating and developing anxiety treatments.