BackgroundMeta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials.Methods and FindingsWe obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups.ConclusionsDrug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.

This article reports an analysis of the efficacy data submitted to the U.S. Food and Drug Administration for approval of the 6 most widely prescribed antidepressants approved between 1987 and 1999. Approximately 80% of the response to medication was duplicated in placebo control groups, and the mean difference between drug and placebo was approximately 2 points on the 17-item (50-point) and 21-item (62-point) Hamilton Depression Scale. Improvement at the highest doses of medication was not different from improvement at the lowest doses. The proportion of the drug response duplicated by placebo was significantly greater with observed cases (OC) data than with last observation carried forward (LOCF) data. If drug and placebo effects are additive, the pharmacological effects of antidepressants are clinically negligible. If they are not additive, alternative experimental designs are needed for the evaluation of antidepressants.

The DASH diet plus reduced sodium intake is recommended to control blood pressure in diverse subgroups.

There have been no studies evaluating incisional NPWT as a prophylactic treatment to prevent infection and wound dehiscence of high-risk surgical incisions. Our data demonstrate that there is a decreased incidence of wound dehiscence and total infections after high-risk fractures when patients have NPWT applied to their surgical incisions after closure. There is also a strong trend for decreases in acute infections after NPWT. Based on our data in this multicenter prospective randomized clinical trial, NPWT should be considered for high-risk wounds after severe skeletal trauma.