Adverse Childhood Experiences and Antidepressant Therapy: A Systematic Review

Adverse childhood experiences (ACEs) increase depression risk and may affect antidepressant (ADM) treatment outcomes; however, cumulative research on each ACE in conjunction with ADM outcomes is lacking. This review aims to examine the relationship between ACEs and ADM. We examined PsychInfo and PubMed/MEDLINE databases from 2010-2025 and identified 26 publications that met review criteria (i.e., peer-reviewed and concurrently examined ACEs and ADM). ACEs were associated with an increased propensity to use ADMs, an interaction between DNA methylation and ADM efficacy, an increased risk of suicide while on ADMs, and ADM responsiveness. The majority of the studies show serotonin modulators and stimulators, selective serotonin reuptake inhibitors, and serotonin norepinephrine reuptake inhibitors are associated with fewer depressive symptoms in ACE survivors. Multiple ACEs and child abuse impaired ADM effectiveness. Yet, genetic links and age when the ACE occurred may explain this vulnerability. These findings should be interpreted with caution, as cumulatively, the research often had smaller sample sizes in the ACE history groups, research often did not test antidepressants against each other, and reported depression symptom changes in the studies may be organic symptom reduction unrelated to treatment. Before medical providers initiate depression treatment, they should ask their patients about ACE history. If patients confide they have these experiences, medical providers will want to consider treatment drug class and establish a plan to monitor the patient carefully for unremitting symptoms, symptoms severity, and suicide risk.