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Childhood Maltreatment May Predict Better Response to IV Ketamine

March 19, 2021

Confirming results from a previous smaller study, researchers found people who reported a history of childhood maltreatment had a more robust response to intravenous (IV) ketamine than other depressed adults seeking ketamine treatment.

The findings were reported in a poster presented at the Anxiety and Depression Association of America 2021 Virtual Conference and discussed at a conference session.

In the study, a sample of 189 adults with treatment-resistant depression received  at least 3 IV ketamine infusions at a private outpatient clinic. Childhood maltreatment history was assessed at baseline using the Childhood Trauma Questionnaire (CTQ), and depression severity was measured at baseline and before each subsequent infusion using the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR).

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Researchers found significant relationships between a larger decrease on the QIDS-SR from baseline to the fourth assessment and higher scores on the CTQ and all 5 of its subscales (sexual abuse, physical abuse, physical neglect, emotional abuse, and emotional neglect.)

They conducted growth mixture modeling to examine patients' specific response trajectories over the 3  infusions and 3 distinct trajectories emerged. In the 1st and largest group of patients, about 40% of the sample were severely depressed at baseline and had a rapid and robust treatment response to three infusions. The second group of patients, about 30% of the sample, were severely depressed at baseline and had minimal response after three infusions. The third group of patients, the remaining 30% of the sample, were moderately depressed at baseline and had minimal response.

“We did find patients that were severely depressed at baseline and fell into the rapid and robust response group reported significantly higher scores of physical abuse on the CTQ than those in the other two groups," said Brittany O’Brien, PhD, Assistant Professor, Baylor College of Medicine, Houston, Texas.

“It appears that patients who report a significant childhood physical abuse history may especially benefit from IV ketamine treatment and given the patients with trauma histories have a lower likelihood of response to first line treatments, ketamine may be a good treatment consideration for severely depressed patients who have significant childhood trauma.”

Ketamine may work better for patients who are typically harder to treat because trauma may induce sensitization of behavioral, motivational, and stress symptoms, Dr. O'Brien said. History of trauma may lower a person’s stress threshold and increase their reactivity to subsequent threshold, resulting in an increase in the likelihood of mood episodes. This expression of sensitization by early stressful events could be blocked by ketamine.

When explaining these findings to a patient, Dr. O'Brien said clinicians can explain it using an easily digestible metaphor. Thinking of trauma as a severe, painful physical wound, when the wound is “scabbed over” that area is then more easily susceptible to subsequent “bumps and scrapes”. For every bump and scrape, the wound is reinjured and becomes more severe and painful. Ketamine may act as a “remarkable” cast or bandage that can protect the wound from additional future stressors. 

“Future research should address the impact of other factors, including substance abuse and more recent trauma experiences, and whether cumulative trauma across the lifespan may also factor into ketamine antidepressant treatment response,” researchers wrote.

—Terri Airov and Meagan Thistle

O’Brien B, Lijffijt M, Murphy N, et al. The impact of childhood maltreatment on depressed adults receiving IV ketamine: A replication study. Poster presented at the Anxiety and Depression Association of America 2021 Virtual Conference; March 18-19, 2021; Virtual.

"Ketamine Treatment in Real World, Clinical Settings." Presented at the Anxiety and Depression Association of America 2021 Virtual Conference; March 19, 2021; Virtual.

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