Transcranial magnetic stimulation appears effective in patients with adverse childhood experiences

A retrospective analysis conducted at Sunnybrook Health Sciences Center in Toronto evaluated the effectiveness of repetitive high-frequency transcranial magnetic stimulation (rTMS) for depression. The results, published in the Journal of Affective Diseasessuggest that rTMS may be effective in the treatment of depression in patients with adverse childhood experiences (ACE).

In general, a “history of negative childhood experiences (ACE) is associated with poorer treatment outcomes in depression,” the researchers wrote.

The Adverse Childhood Experiences Questionnaire (ACE-10) assesses stressful living environments (e.g., parental conflict, substance abuse, mental illness), as well as abuse or neglect by a caregiver that results in harm, threat of harm or potential harm before departure. the age of 18.

Men and women 16 years of age or older with a history of major depressive disorder or bipolar disorder participated in this study, receiving approximately 20 treatments of open high-frequency rTMS to the left dorsolateral prefrontal cortex (DLPFC) 5 times per week for 4 to 6 weeks. The stimulation given was either deep TMS or intermittent theta stimulation, depending on patient preference.

Of 176 eligible treated patients, researchers analyzed 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 the variables or covariates. The average age was 40 and the majority were women.

The mean self-reported ACE score was 2.4, the mean baseline HAMD-17 score was 20.9, the mean number of trials of adequate antidepressants was 4.5, and the 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 at the end of treatment, while controlling for covariates, such as age, gender, refractory, and depression initial. The authors also used multiple logistic regression analysis to assess whether the ACE score affected remission and patient response.

The researchers found that patients’ HAMD-17 scores improved by an average of 8.1 points from the start to the end of acute treatment at 4 or 6 weeks. Continuous ACE was not associated with a significant improvement in HAMD-17 score (0.24; SE=0.33; P > .05). Higher initial depression (0.40; SE = 0.11; P

At the end of acute treatment, 26 of 99 (26.3%) patients were in remission. A higher ACE score was not significantly associated with the odds of remission (odds ratio, 1.12; 95% CI, 0.98-1.35; P > .05). In addition, men had a lower chance of remission than women.

Additionally, using a categorical ACE variable, the researchers found that ACE score at any level (0, 1, 2, 3, ≥4 ACE) was not associated with significant changes in HAMD- 17. A higher baseline HAMD-17 score was associated with improved HAMD-17 (0.35 SE, 0.11, P <.01 additionally having or more aces did not significantly alter the odds of remission compared to those with 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 to higher chances of remission. No variable was found to be significantly associated with response status.

Controlling for age, gender, MSD type, and likely post-traumatic stress disorder (PTSD) status, researchers found that HAMD-17 scores were significantly lower than baseline at week 2, which continued through weeks 4 and 6.

Using ACE subscales based on type of adversity, the researchers found that the presence or absence of neglect, abuse, or dysfunction did not significantly impact the HAMD-17 trajectory at over time taking into account age, sex, type of MSD and likely PTSD status.

The study was limited by the absence of a placebo group. The researchers noted that “although causation cannot be determined from this study, the efficacy of rTMS treatment has already been demonstrated in other randomized trials and meta-analyses.”

Additionally, another limitation was that the ACE questionnaire does not measure the severity, frequency, or duration of adverse events.

Despite the 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 MDD patients receiving high-frequency rTMS on the left DLPFC,” the researchers said. “A history of childhood adversity should not prevent patients with MDD from receiving rTMS treatment for depression.”


Ng E, Wong EHY, Lipsman N, Nestor SM, Giacobbe P. Adverse childhood experiences and outcomes of repetitive transcranial magnetic stimulation for depression. J affect disorder. 2022;320:716-724. doi:10.1016/j.jad.2022.09.153

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