Volume 27 Lesson 8

Neuroendocrine-Based Pharmacotherapy for Depression

Claudio N. Soares, MD, PhD, and George I. Papakostas, MD

Dr. Soares is Director, Women's Health Clinic, and Associate Professor, Department of Psychiatry and Behavioral Neurosciences, McMaster University, Toronto, Canada.

Dr. Papakostas is a Staff Psychiatrist, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Editor's Note

This lesson is a comprehensive review of various neuroendocrine treatment studies for depression focused on 5 areas:

1. hypothalamic-pituitary-thyroid axis (HPT)-active agents,
2. hypothalamic-pituitary-gonadal axis (HPG)-active agents,
3. hypothalamic-pituitary-adrenal axis (HPA)-active agents,
4. melatonergic agents, and
5. vasopressin or vasopressin analogues.

The authors note that psychotropic medications for the treatment of major depression have focused on monoaminergic compounds acting on the serotonergic and noradrenergic systems.

Although medications that enhance serotonin and noradrenalin neurotransmitters remain the mainstay of pharmacotherapy for major depression, recent studies, including the STAR_D study, suggest that monotherapy with these agents is not efficacious in a significant proportion of people with major depression.

Furthermore, sustained recovery is much less common (and treatment refractory major depression much more common) than mental health care providers believed initially.

This review summarizes the literature and provides the rationale and underlying physiologic mechanisms for using various neuroendocrine-based pharmacotherapies both old and new.

Reconsidering these less well studied treatment options reinvigorates our pursuit and development of new medications for the treatment of major depression that are not focused primarily on monoaminergic systems. This may give us ultimately more effective treatments for our patients who suffer from major depression.