Effect of Placebo on Various Anxiety Disorders
From MindLinc Wiki
EBM Type: Therapy Article
Clinical Question: Does placebo have differential effect on different psychiatric disorders?
Methods:
Design - Treatment response and patients' treatment expectancy were examined by using data from 70 patients with obsessive-compulsive disorder, social phobia, or panic disorder who received placebo in three randomized, controlled trials comparing cognitive behavior therapy, medication, and their combination to placebo. These data are obtained from independent RCTs at different medical centers.
Patient Population - Patients from multi-center research clinics.
Inclusion criteria and Exclusion criteria: All studies had similar inclusion criteria (e.g., adults with primary OCD, social phobia, or panic disorder) and exclusion criteria (e.g., no psychosis, mania, or substance abuse). However, unlike the other studies, the panic disorder study (10) did not exclude patients with major depression but did exclude moderate to severe agoraphobia.
Screening/enrollment methods:
Intervention / Control:
- 26 patients with OCD who received placebo in a randomized clinical trial that compared 12 weeks of cognitive behavior therapy, clomipramine, their combination, and placebo (8)
- 60 patients with social phobia who received placebo in a randomized clinical trial that compared 14 weeks of group cognitive behavior therapy, fluoxetine, their combination, placebo, and cognitive behavior therapy plus placebo (9)
- 24 patients with panic disorder who received 12 weeks of placebo in a randomized clinical trial that compared 12 weeks of cognitive behavior therapy, imipramine, their combination, placebo, and cognitive behavior therapy plus placebo (10). Psychopharmacologists saw patients for similar amounts of time in each study, and exposure to anxiety-provoking situations was not systematically encouraged during these visits.
Assessments: All studies included independent raters blind to treatment assignment and used the Clinical Global Impression (CGI) (11) severity and improvement scales, the 17-item Hamilton Depression Rating Scale (12), and a symptom -specific measure: the Yale-Brown Obsessive Compulsive Scale (13) for OCD, the Duke Brief Social Phobia Scale (14) for social phobia, or the Panic Disorder Severity Scale (15) for panic disorder.
Analysis: Non-ITT for presented results but ITT analysis had same results for the between the group comparisons. Effect sizes were calculated for the symptom measures. CGI severity and Hamilton depression scale scores were compared between and within groups by using analyses of variance for pretreatment scores, analyses of covariance for post treatment scores (covarying pretreatment severity), and paired-sample t tests for within-subject change scores. CGI improvement scores were compared by means of chi-square tests of ordinal data. Analyses were conducted separately for the completers and for all randomly assigned patients with any available data by using the last observation carried forward (intent-to-treat group).
VALIDITY:
Data used in three randomized, placebo-controlled trial, with blindness in ratings. Treatment groups appear to be similar at baseline but not explicitly expressed. ITT analysis used but not shown.Completers were analyzed in groups to which they were randomized presented in this paper.Raters were blinded. Pt may have some level of blindness (real pills vs. placebo).Groups are from different pt populations. They appear to be treated similarly outside of placebo intervention but not mentioned.Do the study population characteristics describe your patient? Yes.
Results:
The OCD patients receiving placebo had less symptom improvement than the patients with either social phobia or panic disorder in both the completer (Table 1) and intent-to-treat groups. When the most severe cases were excluded (CGI severity score=6) to eliminate significant pre-treatment CGI severity differences between the patient groups (F=2.2, df=2, 56, p=0.12), the patients with OCD continued to show less improvement at post-treatment than those with social phobia or panic disorder (p<0.01, ANCOVA). Ratios of the effect sizes for active medication and exposure therapy to the effect size for placebo were calculated to determine the treatment responsiveness of the groups. All groups showed at least a 40% larger effect size for the active treatments than for placebo, with the OCD patients showing the largest treatment effects, owing to the smallest placebo effects.
CONCLUSIONS:
- Patients with obsessive-compulsive disorder were less likely to respond to placebo than patients with generalized social phobia or panic disorder. Differential expectancy did not account for these findings.
- Strengths: Three RCTs with similar designs, particularly for the placebo group. Comparison across different studies.
- Weakness: sample sizes are rather small for each group, subjective to errors. Internal validity can be challenging from comparing different studies with different populations. External validity is unknown (generalized). Non ITT analysis might amplify the results.
- Study in context of other available literature and/or current standard-of care: Novel study.
- How will this study affect your management of the putative patient? No effect at this time.
- Next steps for further study of this problem- none.
- In summary, given these limitations, this study provides an insight into different aspects of different anxiety disorders, which may elucidate mechanisms of these disorders and have implications for treatment.
Comments:
