title: A regulatory Apologia--a review of placebo-controlled studies in regulatory submissions of new-generation antidepressants.
abstract: Data on percentage of patients experiencing a relevant response (>50% reduction of the baseline Hamilton Depression Scale (HAMD) score), average baseline severity and sample size were retrieved for all placebo-controlled studies in regulatory submissions of SSRIs and SNRIs between 1984 and 2003. Overall there was 16%-units (95% CI: 12; 20) more responders on active drug compared to placebo. There was no evidence of a diminishing magnitude of effect with lower severity at baseline. With one exception significant differences varying between 13.5 and 19.3%-units were demonstrated for the individual antidepressants. Statistically significant mean differences versus placebo in change in HAMD are not a proper basis for evaluation of clinical relevance and are not sufficient for approval. Differences in the percentage of patients experiencing a clinically relevant response should also be demonstrated. In this respect, the approved SSRIs and SNRIs were found superior to placebo, independent of severity of depression.
authors.affiliation: Medical Products Agency, P.O. Box 26, SE-751 03 Uppsala, Sweden. hans.melander@mpa.se
authors.forename: Hans
authors.initials: H
authors.lastname: Melander
authors.forename: Tomas
authors.initials: T
authors.lastname: Salmonson
authors.forename: Eric
authors.initials: E
authors.lastname: Abadie
authors.forename: Barbara
authors.initials: B
authors.lastname: van Zwieten-Boot
mesh_terms: D000928:Antidepressive Agents / Q000592:standards / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods*; D003863:Depression / Q000188:drug therapy*; D017277:Drug Approval / Q000379:methods / Q000706:statistics & numerical data*; D006801:Humans; D010919:Placebos / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D012720:Severity of Illness Index
chemical_list: D000928:Antidepressive Agents; D010919:Placebos; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors