An update on pharmacotherapy for recurrent depression in 2022.

Introduction: Major depressive disorder remains a major challenge due to its biopsychosocial burden with increased morbidity and mortality. Despite successful treatment options for the acute episode, recurrence rates are high, on average four times in a life span.

Areas Covered: Both pharmacological as non-pharmacological evidence-based therapeutic options to prevent and treat recurrent depression are discussed.

Expert Opinion: Although some risk factors for recurrence are well known, better evidence is needed. Antidepressant medication should be continued after acute treatment at its full therapeutic dose for longer periods, at least 1 year. There are no clear differences between classes of antidepressant medication when treatment is focused on preventing relapse. Bupropion is the only antidepressant with a proven efficacy to prevent recurrence in seasonal affective disorder. Recent findings conclude maintenance subanesthetic ketamine and esketamine treatment can be effective in sustaining antidepressant effect following remission. Furthermore, the pharmacological approach must be integrated with lifestyle interventions, especially aerobic exercise. Finally, combining pharma- and psychotherapy seems to improve outcome. Network and complexity sciences will help to decrease the high recurrence rates of MDD by developing more integrative and personalized approaches.