Pathophysiology
Clinical meaning
The clinician managing PTSD prescribes evidence-based pharmacotherapy, coordinates trauma-focused psychotherapy, manages complex comorbidity, and addresses special populations. The VA/DoD Clinical Practice Guidelines rank PTSD treatments: STRONG recommendation for trauma-focused psychotherapy (PE, CPT, EMDR); WEAK recommendation for SSRI/SNRI pharmacotherapy (sertraline, paroxetine, venlafaxine); AGAINST benzodiazepines, cannabis, and atypical antipsychotics as monotherapy. Pharmacotherapy selection should address the predominant symptom cluster: re-experiencing (SSRI/SNRI, prazosin for nightmares), avoidance (SSRI/SNRI, psychotherapy), negative cognitions (SSRI/SNRI, psychotherapy), and hyperarousal (prazosin, alpha-agonists, SSRI/SNRI). Emerging therapies include: MDMA-assisted psychotherapy (FDA breakthrough therapy designation; Phase 3 trials show 67% no longer meeting PTSD criteria after 3 MDMA-assisted therapy sessions vs 32% placebo); stellate ganglion block (SGB, cervical sympathetic block that may reset sympathetic hyperactivation; promising preliminary evidence); psilocybin-assisted therapy (early investigations for treatment-resistant PTSD); and novel rapid-acting anxiolytics targeting glutamate systems. For treatment-resistant PTSD (failed 2+ adequate SSRI/SNRI trials plus evidence-based psychotherapy), options include: augmentation with prazosin, addition of second-generation antipsychotic (quetiapine, risperidone -- for comorbid psychotic features or severe hyperarousal), and referral for specialized programs.