Meta-regression analysis of paroxetine clinical trial data: does reporting scale matter?

It is unknown to which degree the effect of antidepressant drugs are related to baseline degree of depression, dose level, patient's age, or type of questionnaire used. We explored this for paroxetine.

We used placebo-controlled published and unpublished randomized, double-blind, clinical trials of paroxetine that included moderate to severely depressed patients in an outpatient setting. We specified random-effect models for the Hamilton 17-item and Hamilton 21-item studies separately and jointly.

Among 35 studies retrieved, we considered 26 appropriate for a pooled analysis. Paroxetine (placebo) was given to 2958 (2123) patients. We found that the effects of paroxetine, the differences between score reduction in drug versus placebo group, are smaller in Hamilton 17 (3.8%) than in Hamilton 21 studies (7.0%). The mean difference is 3.2% (95% confidence interval, 0.94%-5.42%), statistically significant by meta-regression analysis. Treatment effects did not change with mean age of patients, early or late studies, baseline score value, or maximal daily dose.

We forward 2 hypotheses for explanation. The Hamilton 21 studies had better selection of patients, thereby smaller effect of regression to the mean than the Hamilton 17 studies, meaning the Hamilton 21 studies reveal true somewhat higher treatment effects. Alternatively, the study groups contained some patients with psychotic symptoms tested for with the Hamilton 21-item questionnaire and thereby becoming decisive for the outcome. If so, paroxetine would have an antipsychotic effect. This is in accordance with some experimental and clinical observations.