Controlled trials in patients with major depressive disorder that compared Hypericum with SSRIs in oral formulations were eligible for inclusion; major depressive disorder diagnosis was according to DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) or ICD-10 (International Statistical Classification of Diseases and Related Health Problems 10th Revision).
Studies were excluded if Hypericum was compared only with placebo or if outcomes did not relate to efficacy or tolerability. Included SSRIs comprised: fluoxetin, fluoxetine, citalopram and sertraline; the most frequent comparison was with fluoxetine. In included studies Hypericum dose ranged from 20mg to 1,800mg per day and SSRI dose from 20 mg to 100mg per day. Outcomes included: clinical response; remission; total adverse events; withdrawals due to adverse events; and mean reduction in Hamilton Rating Scale for Depression score from baseline. Mean patient age, where stated, ranged from 37.3 to 69 years. Depression severity ranged from mild to severe. In the included trials, treatment duration was from four to 12 weeks.
Three reviewers independently selected the studies for inclusion; there were no disagreements.