The authors found that TCAs were the most effective drug, followed by SNRIs, MAOIs, SSRIs and atypical antidepressants.
The largest and most expensive study conducted to date, on the effectiveness of pharmacological treatment for depression, was commissioned by the National Institute of Mental Health. Participants in the trial were recruited when they sought medical care at general medical or psychiatric clinics.
A 2015 systematic review of add-on therapies for treatment-resistant depression concluded that quetiapine and aripiprazole have the strongest evidence-base supporting their efficacy, but they are associated with additional treatment-related side effects when used as an add-on therapy.
A 2008 Cochrane Collaboration review on St John's wort (specifically, any extracts which contain Hypericum perforatum), and a 2015 meta-analytic systematic review by some of the same authors, both concluded that it: has superior efficacy to placebo in treating depression; is as effective as standard antidepressant pharmaceuticals for treating depression; and has fewer adverse effects than other antidepressants.
Conflicting results have arisen from studies analyzing the efficacy of antidepressants by comparisons to placebo in people with acute mild to moderate depression.
Stronger evidence supports the usefulness of antidepressants in the treatment of depression that is chronic (dysthymia) or severe.
The guidelines recommend that antidepressant treatment should be considered for: The guidelines further note that antidepressant treatment should be used in combination with psychosocial interventions in most cases, should be continued for at least six months to reduce the risk of relapse, and that SSRIs are typically better tolerated than other antidepressants.
American Psychiatric Association treatment guidelines recommend that initial treatment should be individually tailored based on factors that include severity of symptoms, co-existing disorders, prior treatment experience, and patient preference.Researchers Irving Kirsch and Thomas Moore have contested the pharmacological activity of antidepressants in the relief of depression, and state that the evidence is most consistent a role as active placebos.Their study consisted of a meta analysis incorporating data from both published studies and unpublished data obtained from the FDA via a Freedom of Information Act request.Overall, antidepressant pills worked 18% better than placebos, a statistically significant difference, but not one that is clinically significant. FDA published a systematic review of all antidepressant maintenance trials submitted to the agency between 19.Another study focusing on paroxetine (Paxil) and imipramine found that antidepressant drugs were only slightly better than placebo in cases of mild or moderate depression they surveyed but offered "substantial" benefit in those with severe depression. The authors concluded that maintenance treatment reduced the risk of relapse by 52% compared to placebo, and that this effect was primarily due to recurrent depression in the placebo group rather than a drug withdrawal effect.A review commissioned by the National Institute for Health and Care Excellence concluded that there is strong evidence that SSRIs have greater efficacy than placebo on achieving a 50% reduction in depression scores in moderate and severe major depression, and that there is some evidence for a similar effect in mild depression.