Post-traumatic stress disorder - Pathophysiological aspects and pharmacological approaches to treatment

Post-traumatic stress disorder (PTSD) is a syndrome of psychophysiological sequelae occurring in the aftermath of severe emotional trauma. Phenomenologically, symptoms occur in 3 clusters: re-experiencing, avoidance and hyperarousal. Other psychiatric disorders such as depression, panic disorder and substance abuse frequently co-occur with PTSD. Treatment strategies for PTSD are often multimodal and attempt to integrate biological, behavioural, cognitive, psychodynamic and social formulations. Pharmacotherapy must target specific symptoms in all 3 clusters, and address the presence of comorbid psychiatric disorders. Psychotropic medication can facilitate psychotherapeutic work, or serve as the primary modality in a biologically based approach to treatment. Specific medications used in the treatment of PTSD span a broad spectrum of pharmacological agents. The most empirically studied agents, tricyclic antidepressants and monoamine oxidase inhibitors, demonstrate a definite but limited impact on specific PTSD symptoms. For the patient who presents in an acute symptomatic state, benzodiazepine anxiolytics may be appropriate. For longer term treatment, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs), particularly fluoxetine, appear to have broader spectrum therapeutic effects on specific PTSD symptom clusters. Both antidepressants and anxiolytics have, in some studies, shown beneficial effects on depressive symptoms and anxiety, without measurable impact on the symptoms more specific to PTSD. Maintenance pharmacotherapy frequently requires a multidrug regimen; an SSRI may serve as the primary agent, with adjunctive agents targeting residual hyperarousal and re-experiencing symptoms. Benzodiazepines, sedating tricyclic or antihistamine compounds, and the noradrenergic drugs clonidine and propranolol are used in this way. Buspirone, a serotonergic anxiolytic, may serve a similar role for some patients, and cyproheptadine in particular appears to be helpful for nightmares. The antikindling agents carbamazepine and valproic acid (sodium valproate) have also been reported to be beneficial, and may provide an alternative for patients with persistent hyper-reactivity and explosiveness that have not responded to other treatments.