Early Life Trauma May Predict Later Response to Antidepressants
Abstract
Children who experienced abuse between ages four and seven were found to be about 1.6 times less likely to respond to antidepressants, with sertraline being particularly ineffective.
Exposure to abuse in childhood can have long-lasting effects, especially with regard to mental health. Research has shown that childhood abuse not only increases the risk of depression over the lifetime, but children who are abused often experience an earlier onset of depression that is more severe and often results in poorer outcomes.
New evidence now suggests that abuse can also greatly reduce response to antidepressants, with particularly poor outcomes for sertraline.
These findings, published in Translational Psychiatry, came from an analysis of over 1,000 adults who were part of the international Study to Predict Optimized Treatment in Depression (iSPOT-D). Participants were randomly assigned to receive escitalopram, sertraline, or venlafaxine for eight weeks. Researchers used the Early-Life Stress Questionnaire (ELSQ) to assess participants’ exposure to abuse or other trauma and the age at which such events first took place.
The researchers found that people with depression who experienced childhood abuse of any type (physical, emotional, or sexual) showed a lower rate of medication response and remission compared with depressed patients who had no trauma exposure or those who were exposed to non-abusive trauma, such as parental divorce or a serious injury as a child.
When the abuse occurrence was broken down by discrete age groups, the researchers found that abuse specifically from the ages of 4 to 7 was related to poor medication outcomes, with patients taking sertraline showing the lowest rates of improvement. In contrast, there were no significant associations between poor medication outcomes and abuse that occurred between ages 8 to 12 or 13 to 17.
When treating depressed patients with a history of early childhood abuse, Leanne Williams, Ph.D., says clinicians may want to consider alternative medications and adjunctive therapies that address the underlying trauma.
“These results do not imply that abuse occurring in later childhood has no ill effects,” lead author Leanne Williams, Ph.D., a professor of psychiatry and behavioral sciences at Stanford University, told Psychiatric News. “They just indicate that abuse during this critical age range may have the most significant impact on future outcomes.”
In fact, patients who experienced abuse between ages 4 and 7 represented only 18 percent of all iSPOT-D participants who responded to treatment after eight weeks and less than 16 percent of patients who achieved remission.
“I believe these odds make the chance of response too low to meaningfully consider these antidepressants as a first-line treatment for patients who experienced early abuse or neglect,” Williams said. “Consideration should be given to alternative medications plus adjunctive therapies that address the trauma issues as well as the current experience of depression.”
Trauma-focused behavioral therapies or interventions for posttrauma–related stress are two possible alternatives for depressed patients with a history of early child abuse, Williams noted. Once the experiences of trauma are addressed, antidepressants may prove to be more effective for this population, she said.
Before considering treatment, clinicians must first identify patients with a history of abuse, Williams added. She noted that a thorough patient evaluation is considered commonplace among psychiatric professionals, but many patients seeking care for depression are being treated in nonspecialty settings that may not delve deeply into the past—despite the potential importance of these aspects of life history.
Williams suggested that memory and emotional development between ages 4 and 7 may offer one explanation as to why abuse during these early years appears to have the greatest effects on response to antidepressants later in life. “At these ages, [children] can begin consolidating memories of their experiences, but they do not yet have the capacity to reflect on and contextualize their experience of the trauma,” she said.
Williams acknowledged the need for more longitudinal studies to explore how childhood trauma may alter circuits in the brain over time, possibly leading to an increased risk of depression and a decreased response to treatment.
Members of her research group are hoping to make use of such data as part of a “precision psychiatry and neuroscience” program they are developing, in which treatment choices can be tailored to the needs of the patient based on their symptoms, brain circuitry, and trauma history.
This study was supported by Brain Resource Ltd. ■
