Ketamine Leaves BDNF Unchanged

The mystery of depression deepens as a new study finds no change in brain-derived neurotrophic factor (BDNF) levels as patients improve following ketamine treatment.

Researchers at the Mood and Anxiety Disorders Program at the National Institute of Mental Health (NIMH) previously showed in clinical studies that ketamine, an anesthetic given by intravenous (IV) infusion, has a rapid antidepressant effect in a subgroup of patients with treatment-resistant major depressive disorder. Meanwhile, a body of research evidence links decreased levels of BDNF in the brain and peripheral blood with major depression. For example, antidepressants have been shown to regulate BDNF levels, and some studies have found that patients with depression have lower BDNF levels in peripheral blood than do control subjects.

In a new study published September 19 in the online Journal of Clinical Psychiatry, the same group of NIMH scientists demonstrated that the antidepressant action of ketamine appears to bypass BDNF altogether.

The authors gave a single dose of ketamine IV infusion at 0.5 mg/kg to 23 adult patients with treatment-resistant major depressive disorder and measured their BDNF level in blood at 60 minutes before and 40, 80, 120, and 230 minutes after ketamine infusion. Treatment resistance was defined as failing at least two adequate trials of antidepressants.

Eleven of the 23 patients were deemed treatment responders, defined as having at least a 50 percent reduction from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score at two hours after the infusion. No significant change in BDNF levels was observed in either the responders or the nonresponders during the study, which was carried out between October 2006 and May 2008. The authors found no statistical correlation between the MADRS score and BDNF level at any time point.

The rapid therapeutic effect of ketamine is thought to involve the immediate activation of a glutamatergic receptor known as AMPA receptor. How this pathway and BDNF fit into the picture of the neurochemical process of depression is not yet understood. “Further studies in this area are urgently needed,” the authors wrote. ▪