Novel Antidepressant in the Pipeline: NMDA Receptor Antagonists

Author: Brian Gabriel

In a given year, approximately 26.2% of Americans (or roughly 1 in 4 adults) will suffer from a mental disorder. The most prevalent mental disorder, major depressive disorder, strikes anywhere from 6.7% to 9.5% of U.S. adults each year. 15% of these individuals will commit suicide, making depression the second-largest cause of adult mortality in the U.S. following coronary artery disease (furthermore, studies are beginning to illuminate the positive correlation between these two diseases).

Historically, psychopharmaceuticals have putatively targeted the “monoamines” of the brain; namely serotonin, norepinephrine, and dopamine. The first widespread class of antidepressants, monoamine oxidase inhibitors (MAOIs), was serendipitously discovered to benefit those suffering from depression after patients treated with these antihypertensive medications reported elevated moods. MAOIs are fraught with side-effects, however, including the potentially fatal hypertensive crisis. Because of side-effects, MAOIs are less frequently prescribed today. Similarily, tricyclic antidepressants are also characterized by numerous burdensome side effects including fatal cardiotoxicity in overdose. Finally, while safer than MAOIs and tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) present additional difficulties including a delayed onset of action. While subtle variations on SSRIs have developed (including selective serotonin and norepinephrine reuptake inhibitors-SNRIs), truly novel antidepressants outside the paradigm of monoamines are currently lacking. Below is a brief discussion of one such novel class of antidepressant currently in development.

Open-Label Placebo Provides Therapeutic Benefit

Author: Brian Gabriel

Investigators recently compared an open-label placebo intervention to a no-treatment control for the treatment of irritable bowel syndrome (IBS) as detailed here. Surprisingly, investigators found the open-label placebo superior to the no-treatment control. Specifically, upon conclusion of the study, participants receiving the open-label placebo demonstrated statistically significant improvements in IBS symptoms over the no-treatment control group (as measured by several IBS scales).

Critically, all participants were coached as to the benefit of placebo pills throughout the study. For example, participants were told “placebo pills, something like sugar pills, have been shown in rigorous clinical testing to produce significant mind-body self-healing processes.” Additional coaching by clinical providers (either gastroenterologists or nurse-practitioners) expounded the benefit of placebo pills with statements such as “the body can automatically respond to placebo pills,” and “the placebo effect is powerful.”