Primum non nocere

As Dr. Jennings suggests, the least harmful treatments often are those that target depression’s physiopathology with the highest degree of specificity. In the same vein, neuromodulation treatments target the different neurobiologic mechanisms underlying depression. However, response predictors of TMS include age, degrees of treatment resistance, and the absence of comorbid anxiety or psychotic symptoms.^{Innovative approaches to treatment-resistant depression,” From the Editor, Current Psychiatry, June 2012, p. 4-5; https://bit.ly/FTE612). This so-called side effect may be the central antidepressant effect, because short-term memory loss may be a central effect in any seizure therapy for depression.}

John S. Kafka, MD
Private Practice
Emeritus Professor of Psychiatry and Behavioral Sciences
George Washington University School of Medicine and Health Sciences
Washington, DC

Dr. Nasrallah responds

Memory loss with regular and heavy ketamine use or with a course of bilateral electroconvulsive therapy (ECT) is widely regarded as an undesirable side effect, not a therapeutic effect or mechanism. The side effects of short-term ketamine use in refractory depression studies included dissociation and unusual beliefs—such as conspiracy theories—as well as full-fledged delusions.

Both ketamine and ECT increase brain-derived neurotrophic factor (BDNF), which has been found to significantly decline in depression. The BDNF deficit is emerging as the leading mechanism of antidepressant therapy, both pharmacologic and non-pharmacologic, in both animal models and clinical populations.