Predicting stable treatment response in patients with major depression treated with Hypericum extract WS 5570/5572

Objective: Recent research with several synthetic antidepressants indicates that early improvement during the initial weeks of treatment may be a highly sensitive predictor of therapeutic success in major depression. We investigated whether early improvement is sensitive and specific in predicting sustained response and non-response to antidepressant treatment with Hypericum extract WS (R) 5570/5572 and whether the results reported for synthetic antidepressants apply to these Hypericum extracts as well. Methods: We analyzed original data of 3 double-blind, randomized trials including a total of 594 adult outpatients suffering from major depression according to DSM-IV criteria, who received well-characterized Hypericum extract preparations WS (R) 5570, WS (R) 5572, WS (R) 5573 or placebo for 6 weeks. The main outcome measure was the prediction of a sustained >= 50% decrease of the Hamilton Depression Scale (HAM-D) total score versus baseline ('sustained response') by the presence of >= 20% HAM-D total score improvement after 1 and 2 weeks of treatment ('early improvement'). Results: For Hypericum extract, early improvement had a sensitivity of 87% (95 confidence interval [CI], 82-93%) and a specificity of 54% (95% Cl, 45-62%) at day 14, and a sensitivity of 43% (95% CI, 35-51%) and a specificity of 86% (95% Cl, 80-92%) at day 7 for predicting sustained response. After 2 weeks of treatment, 78% (95% Cl, 69-87%) of the patients who failed to improve did not show sustained response later during treatment. Conclusion: A substantial fraction of the patients treated with Hypericum extracts WS (R) 5570/5572 showed a meaningful reduction of depressive symptoms during the first two weeks of treatment (early improvement), which was found to be a sensitive predictor of sustained response. The results determined for the herbal extracts were comparable to those for effective synthetic antidepressants investigated previously.