Supplementary Pharmacotherapy for the Behavioral Abnormalities Caused by Stressors in Humans, Focused on Post-Traumatic Stress Disorder (PTSD)

Used as a supplement to psychotherapy, pharmacotherapy that addresses all of the known metabolic and genetic contributions to the pathogenesis of psychiatric conditions caused by stressors would require an inordinate number of drugs. Far simpler is to address the abnormalities caused by those metabolic and genetic changes in the cell types of the brain that mediate the behavioral abnormality. Relevant data regarding the changed brain cell types are described in this article and are derived from subjects with the paradigmatic behavioral abnormality of PTSD and from subjects with traumatic brain injury or chronic traumatic encephalopathy. If this analysis is correct, then therapy is required that benefits all of the affected brain cell types; those are astrocytes, oligodendrocytes, synapses and neurons, endothelial cells, and microglia (the pro-inflammatory (M1) subtype requires switching to the anti-inflammatory (M2) subtype). Combinations are advocated using several drugs, erythropoietin, fluoxetine, lithium, and pioglitazone, that benefit all of the five cell types, and that should be used to form a two-drug combination, suggested as pioglitazone with either fluoxetine or lithium. Clemastine, fingolimod, and memantine benefit four of the cell types, and one chosen from those could be added to the two-drug combination to form a three-drug combination. Using low doses of chosen drugs will limit both toxicity and drug-drug interactions. A clinical trial is required to validate both the advocated concept and the choice of drugs.