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Multitarget botanical pharmacotherapy in major depression

a toxic brain hypothesis

Tang, Siu W.a; Tang, Wayne H.b; Leonard, Brain E.c

International Clinical Psychopharmacology: November 2017 - Volume 32 - Issue 6 - p 299–308
doi: 10.1097/YIC.0000000000000186

A significant number of patients with major depression do not respond optimally to current antidepressant drugs. As depression is likely to be a heterogeneous disorder, it is possible that existing neurotransmitter-based antidepressant drugs do not fully address other pathologies that may exist in certain cases. Biological pathologies related to depression that have been proposed and studied extensively include inflammation and immunology, hypercortisolemia, oxidative stress, and impaired angiogenesis. Such pathologies may induce neurodegeneration, which in turn causes cognitive impairment, a symptom increasingly being recognized in depression. A neurotoxic brain hypothesis unifying all these factors may explain the heterogeneity of depression as well as cognitive decline and antidepressant drug resistance in some patients. Compared with neurotransmitter-based antidepressant drugs, many botanical compounds in traditional medicine used for the treatment of depression and its related symptoms have been discovered to be anti-inflammatory, immunoregulatory, anti-infection, antioxidative, and proangiogenic. Some botanical compounds also exert actions on neurotransmission. This multitarget nature of botanical medicine may act through the amelioration of the neurotoxic brain environment in some patients resistant to neurotransmitter-based antidepressant drugs. A multitarget multidimensional approach may be a reasonable solution for patients resistant to neurotransmitter-based antidepressant drugs.

aDepartment of Psychiatry, University of California, Irvine, California, USA

bInstitute of Brain Medicine, Central, Hong Kong

cDepartment of Pharmacology and Therapeutics, National University of Ireland, Galway, Galway, Ireland

Correspondence to Siu W. Tang, MD, PhD, Department of Psychiatry, University of California, North Campus Psychiatry Trailer, Zot 1681 Irvine, CA 92697-1681, USA Tel: +1 949 824 3557; e-mail:

Received February 10, 2017

Accepted June 7, 2017

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