Repetitive transcranial magnetic stimulation offers an alternative solution that may be effective for treating depression in patients with adverse childhood experiences.
A retrospective analysis conducted at Sunnybrook Health Sciences Centre in Toronto evaluated the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) for depression. The results, published in the Journal of Affective Diseases, suggest that rTMS may be effective in treating depression in patients with adverse childhood experiences (ACEs).
In general, a “history of adverse childhood experiences (ACEs) is associated with poorer treatment outcomes in depression,” the researchers wrote.
The Adverse Childhood Experiences Questionnaire (ACE-10) assesses stressful living environments (eg, parental conflict, substance abuse, mental illness), as well as abuse or neglect from a caregiver that leads to harm, threats of harm, or potential harm before the age of 18.
Men and women 16 years or older with a history of major depressive disorder or bipolar disorder were participants in this study, receiving around 20 open-label, high-frequency rTMS treatments to the left dorsolateral prefrontal cortex (DLPFC) 5 times a week for 4 to 6 weeks. The stimulation given was either deep TMS or intermittent theta burst stimulation, according to the patient’s preference.
Out of 176 eligible treated patients, the researchers analyzed the data from 116 participants who had a baseline ACE score, a baseline Hamilton Rating Scale for Depression (HAMD-17) score, and a HAMD-17 score at the end of acute treatment. Of these, 99 patients had information on variables or covariates available. The mean age was 40 years, and the majority were women.
Mean self-reported ACE score was 2.4, mean baseline HAMD-17 score was 20.9, mean number of adequate antidepressant trials was 4.5, and mean CIRS-G score (to measure medical comorbidity) was 3.6.
Multiple linear regression analysis assessed the impact of ACE score on improvements in HAMD-17 score by the end of treatment, while also accounting for covariates, such as age, gender, refractoriness, and baseline depression. The authors also used multiple logistic regression analysis to assess whether ACE score affected remission and response of the patient.
The researchers found that patients’ HAMD-17 scores improved by an average of 8.1 points from baseline to the end of acute treatment at 4 or 6 weeks. Continuous ACE was not associated with significant improvement in HAMD-17 score (0.24; SE = 0.33; P > .05). Higher baseline depression (0.40; SE = 0.11; P <.001) was associated with a greater improvement of HAMD-17 score from baseline to end of acute treatment.
By the end of acute treatment, 26 of 99 (26.3%) of patients remitted. Higher ACE score was not significantly associated with odds of remission (odds ratio, 1.12; 95% CI, 0.98-1.35; P > .05). Additionally, men had lower odds of remission than women.
Additionally, using a categorical ACE variable, the researchers found that ACE score at any level (0, 1, 2, 3, ≥4 ACEs) was not associated with significant changes to HAMD-17 score. A higher baseline HAMD-17 score was associated with improvement in HAMD-17 (0.35 SE, 0.11, P <.01). Furthermore, having 1, 2, 3, or 4 or more ACEs did not significantly change the odds of remission relative to those with 0 ACEs.
However, in an alternative model including all covariates, perceived social status was associated with higher odds of remission, baseline depression was associated with lower odds of remission, and having 4 or more ACEs was associated with higher odds of remission. No variables were found to be significantly associated with response status.
Accounting for age, gender, TMS type, and probable posttraumatic stress disorder (PTSD) status, the researchers found that HAMD-17 scores were significantly lower than baseline by week 2, which continued in weeks 4 and 6.
Using ACE subscales based on adversity type, the researchers found that the presence or absence of neglect, abuse, or dysfunction did not significantly impact HAMD-17 trajectory over time when accounting for age, gender, TMS type, and probable PTSD status.
The study was limited by not using a placebo group. The researchers noted that “although causality cannot be determined from this study, the efficacy of rTMS treatment has been previously demonstrated in other randomized trials and meta-analysis.”
Additionally, another limitation was that the ACE questionnaire does not measure severity, frequency, or duration of adverse events.
Despite limitations, this study suggests that rTMS may prove effective in treating depression in patients with ACE.
“High levels of self-reported childhood adverse experiences were not associated with worse antidepressant outcomes in patients with MDD receiving high-frequency rTMS to the left DLPFC,” the researchers stated. “A history of childhood adversity should not preclude patients with MDD from rTMS treatment for depression.”
Ng E, Wong EHY, Lipsman N, Nestor SM, Giacobbe P. Adverse childhood experiences and repetitive transcranial magnetic stimulation outcomes for depression. J Affect Disord. 2022;320:716-724. doi:10.1016/j.jad.2022.09.153