Objective: This review aimed to measure the degree of placebo response in panic disorder. Data Sources: We searched major databases up to 31 January 2021, for randomized pharmacotherapy trials published in English. Study Selection: A total of 43 studies met inclusion criteria to be in the analysis (with 174 separate outcome measurements). Data Extraction: Changes in outcome measures from baseline in the placebo group were used to estimate modified Cohen’s d effect size. Results: A total of 43 trials (2392 subjects, 174 outcomes using 27 rating scales) were included in the meta-analysis. Overall placebo effect size was 0.57 (95% confidence interval = [0.50, 0.64]), heterogeneity ( I2: 96.3%). Higher placebo effect size was observed among clinician-rated scales compared to patient reports (0.75 vs 0.35) and among general symptom and anxiety scales compared to panic symptoms and depression scales (0.92 and 0.64 vs 0.56 and 0.54, respectively). There was an upward trend in effect size over the publication period ( r = 0.02, p = 0.002) that was only significant among clinician-rated scales ( r = 0.02, p = 0.011). There was no significant publication bias, Egger’s test ( p = 0.08). Conclusion: We observed a substantial placebo effect size in panic disorder. This effect was more prominent for some aspects of panic disorder psychopathology than for others and was correlated with the source of the assessment and publication year. This finding has implications both for research design, to address the heterogeneity and diversity in placebo responses, and for clinical practice to ensure optimal quality of care. Systematic review registration number: PROSPERO, CRD42019125979.

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Background Post-stroke depressive symptoms are prevalent and impairing, and elucidating their course and risk factors is critical for reducing their public health burden. Previous studies have examined the course of post-stroke depression, but distinct depressive symptom dimensions (eg, somatic symptoms, negative affect [eg, sadness], anhedonia [eg, loss of interest]) may vary differently over time. Objective The present study examined within-person and between-person associations between depressive symptom dimensions across 3 timepoints in the year following discharge from in-patient rehabilitation hospitals, as well as the impact of multiple clinical variables (eg, aphasia). Methods Stroke survivors completed the Center for Epidemiologic Depression Scale (CES-D) at discharge from post-stroke rehabilitation (“T1”) and at 3-month (“T2”) and 12-month (“T3”) follow-ups. Scores on previously identified CES-D subscales (somatic symptoms, anhedonia, and negative affect) were calculated at each timepoint. Random intercept cross-lagged panel model analysis examined associations between symptom dimensions while disaggregating within-person and between-person effects. Results There were reciprocal, within-person associations between somatic symptoms and anhedonia from T1 to T2 and from T2 to T3. Neither dimension was predictive of, or predicted by negative affect. Conclusions The reciprocal associations between somatic symptoms and anhedonia may reflect a “vicious cycle,” and suggest these 2 symptom dimensions may be useful indicators of risk and/or intervention targets. Regularly assessing depression symptoms starting during inpatient rehabilitation may help identify stroke survivors at risk for depression symptoms and facilitate early intervention.