Review: hypericum extracts are safer and lead to fewer adverse effects than older standard antidepressants, but have similar tolerability to SSRIs.

MAIN RESULTS Thirty five published RCTs met criteria for inclusion in the review (24 trials comparing hypericum extracts with placebo, seven comparing hypericum extracts with older antidepressants, and six comparing hypericum with selective serotonin reuptake inhibitors (SSRIs)). Compared with placebo, hypericum resulted in similar numbers of dropouts due to adverse effects (24 RCTs, 8/1334 (0.6%) with hypericum v 15 (1.2%) with placebo, OR 0.61, 95% CI 0.28 to 1.31). There was no significant difference between hypericum and placebo in the number of people reporting adverse effects (236/1123 (21%) with hypericum v 254/1077 (23.6%) with placebo, OR 0.79, 95% CI 0.61 to 1.03). Compared with older antidepressants, treatment with hypericum led to fewer dropouts for adverse effects and fewer reports of adverse effects (seven RCTs, dropouts for adverse effects: 14/615 (2.3%) with hypericum v 52/616 (8.4%) with amitriptyline, imipramine, or maprotiline, OR 0.25, 95% CI 0.14 to 0.45; reports of adverse effects: 174/615 (11.1%) with hypericum v 301/616 (15.6%) with amitriptyline, imipramine, or maprotiline, OR 0.39, 95% CI 0.31 to 0.50). There were no significant differences between hypericum and SSRIs in numbers dropping out for adverse effects or total adverse effects reported, though the trend was for fewer adverse effects with hypericum (dropouts due to adverse effects: OR 0.60, 95% CI 0.31 to 1.15, total numbers reporting adverse effects: OR 0.75, 95% CI 0.52 to 1.08).