The Impact of Childhood Maltreatment on Intravenous Ketamine Outcomes for Adult Patients with Treatment-Resistant Depression

Abstract

Childhood maltreatment is associated with a poor treatment response to conventional antidepressants and increased risk for treatment-resistant depression (TRD). The N-methyl-D-aspartate receptor (NDMAR) antagonist ketamine has been shown to rapidly improve symptoms of depression in patients with TRD. It is unknown if childhood maltreatment could influence ketamine’s treatment response. We examined the relationship between childhood maltreatment using the Childhood Trauma Questionnaire (CTQ) and treatment response using the Quick Inventory of Depressive Symptoms–Self Report (QIDS-SR) in TRD patients receiving intravenous ketamine at a community outpatient clinic. We evaluated treatment response after a single infusion (n = 115) and a course of repeated infusions (n = 63). Repeated measures general linear models and Bayes factor (BF) showed significant decreases in QIDS-SR after the first and second infusions, which plateaued after the third infusion. Clinically significant childhood sexual abuse, physical abuse, and cumulative clinically significant maltreatment on multiple domains (maltreatment load) were associated with better treatment response to a single and repeated infusions. After repeated infusions, higher load was also associated with a higher remission rate. In contrast to conventional antidepressants, ketamine could be more effective in TRD patients with more childhood trauma burden, perhaps due to ketamine’s proposed ability to block trauma-associated behavioral sensitization.

Recognizing the importance of childhood maltreatment as a critical factor in psychiatric diagnoses, treatment, research, prevention, and education

“…Nemeroff et al [22] reported that adults with chronic depression and early life stress had a more beneficial response to Cognitive Behavioral Analysis System of Psychotherapy (CBASP) than nefazadone and they appeared to have had a more favorable response to CBASP than chronically depressed individuals without early life stress. Likewise, O'Brien et al [33] recently reported that participants with refractory depression and CM had a substantially better response to intravenous ketamine than refractory depressed individuals without CM. More data like these are desperately needed to guide treatment and an improved classification system will facilitate and empower this essential research.…”

Effects of Chronic Cannabidiol Treatment in the Rat Chronic Unpredictable Mild Stress Model of Depression

“…Drugs acting on monoamine neurotransmission have dominated the treatment of depression for decades; however, a significant percentage of depressive patients show resistance to pharmacotherapy [17]. Recently, ketamine and its enantiomer S-ketamine have been rediscovered as rapid acting antidepressants with demonstrated efficiency in treatment-resistant depression [18,19]. CBD has also been reported to produce antidepressant-like effects after a single dose [15,20,21].…”

Oral S-ketamine effective after deep brain stimulation in severe treatment-resistant depression and extensive comorbidities

“…7 However, the psychotic manifestations, such as perceptual abnormalities, disordered thought and dissociation after ketamine administration are transient and seem to be well tolerated, even in patients with psychotic vulnerability. [8][9][10] Of note, ketamine is also suggested to be more effective in patients with a higher childhood trauma burden, 11 which is a known risk factor for the development of TRD and suicide. 12 Repeated oral S-ketamine was safely combined with other psychiatric drugs and even with the Case report experimental neuromodulation treatment of DBS.…”