Etiology and biology of post-traumatic stress disorder: Implications for treatment

The biology of PTSD does not conform to the traditional model of the stress response and is distinct from that observed in other psychiatric disorders. In addition, the biologic alterations in PTSD can evolve over time. It is not clear which changes occur following trauma exposure and which occur in response to the development of PTSD. Some biologic alterations may also reflect vulnerability for PTSD and the development of subsequent comorbid psychiatric conditions. There is also evidence that there may be biologic subgroups within PTSD that may have significant treatment implications. The pharmacologic literature in PTSD is relatively small but is growing quickly as the field develops. The older studies in male veterans were important in demonstrating that medications can be quite effective in treating circumscribed symptoms of PTSD and lead to overall global improvement. The newer studies involving nonveteran populations of all trauma types are better designed with large sample sizes studying the SSRIs and the treatment of PTSD. One of the conclusions that can be drawn is that of the medications that have been tried to treat PTSD to date, the SSRIs seem to be the most promising, reducing all three symptom clusters. The medications that appear to work best on intrusive symptoms but not on the other clusters are the MAOIs and TCAs. Hyperarousal symptoms also appear to respond to mood stabilizers and adrenergic agents, but these medications appear to have little effectiveness on the other symptom clusters. The fact that different medications target different core symptoms of PTSD has been interpreted as reflecting the complex pathophysiology of this disorder. It may be that medications with specific effects in some neurotransmitter systems may have particular effects on those symptoms that are primarily mediated by those systems. Indeed, some classes of medications may be more effective in treating certain subgroups of PTSD and not others. Although more controlled studies need to be undertaken with other classes of medications that are currently being used in other disorders, studies involving agents of novel biologic action, specifically developed based on the biologic profile of PTSD, should also be pursued. Future studies must also address the interaction of psychopharmacology and psychosocial treatments. Other questions concern the appropriate duration for pharmacotherapy, the effects of discontinuing medications on PTSD symptoms, and relapse prevention.