Baseline depression severity affects treatment benefit of antidepressant drugs, meta-analysis shows

Among individuals with depression, the magnitude of benefit gained from antidepressant drug therapy depends on the severity of a patient's symptoms, with treatment having an overall minimal effect when used in patients whose symptoms are mild or moderate, according to a new meta-analysis. However, patients with very severe depression appear to experience a substantial therapeutic benefit. For the analysis, investigators identified six trials that compared treatment with an approved...

Among individuals with depression, the magnitude of benefit gained from antidepressant drug therapy depends on the severity of a patient's symptoms, with treatment having an overall minimal effect when used in patients whose symptoms are mild or moderate, according to a new meta-analysis. However, patients with very severe depression appear to experience a substantial therapeutic benefit.

For the analysis, investigators identified six trials that compared treatment with an approved antidepressant (a selective serotonin reuptake inhibitor or a tricyclic antidepressant) to placebo among adult outpatients with major or minor depressive disorder. The included studies lasted at least six weeks and used the Hamilton Depression (Ham-D) rating scale as a measure of efficacy. The studies' original authors also provided the researchers with individual patient-level data.

In all, 718 patients were represented, of which 434 had been treated with an antidepressant and 284 with placebo. Baseline Ham-D scores ranged from 10 to 39. Mild to moderate depression was defined as an Ham-D score of 18 or less, severe depression as a score that ranged from 19 to 22 and very severe depression as a score of 23 or greater.

The analysis revealed that the patients with Ham-D scores of less than 23 experienced only a small effect with antidepressant treatment relative to placebo. However, once baseline Ham-D scores reached 25, the magnitude of the effect of antidepressant treatment became clinically significant, according to an effect threshold established by the U.K.'s National Institute for Clinical Excellence.

The researchers also determined that for one additional patient in the treatment group to experience an improved outcome relative to placebo, 16 patients would first need to be treated among those with mild to moderate depression and 11 would need to be treated among those with severe depression. However, among the patients with very severe depression, the number needed to treat was only four.

"[E]fforts should be made to clarify to clinicians and prospective patients that whereas antidepressant medication can have a substantial effect with more severe depressions, there is little evidence to suggest that they produce specific pharmacological benefit for the majority of patients with less severe acute depressions," the authors of the study concluded.

The findings appeared in the Jan. 6 issue of JAMA.