REVIEW ARTICLESMultitarget botanical pharmacotherapy in major depression a toxic brain hypothesisTang, Siu W.a; Tang, Wayne H.b; Leonard, Brain E.cAuthor Information 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: [email protected] Received February 10, 2017 Accepted June 7, 2017 International Clinical Psychopharmacology: November 2017 - Volume 32 - Issue 6 - p 299-308 doi: 10.1097/YIC.0000000000000186 Buy Metrics Abstract 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. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.