PTSD is a debilitating disorder with complex underlying pathophysiology involving neurotransmitters, neurocircuitry, and neuroanatomical pathways. Only two SSRIs are currently FDA-approved for its treatment. The authors review novel and emerging treatments targeting non-serotonergic pathways, including drugs in development (BI 1358894, BNC-210, PRAX-114, JZP-150, LU AG06466, NYV-783, PH-94B, SRX246, TNX-102), established agents being investigated for PTSD (brexpiprazole, cannabidiol, doxasoin, ganaxolone, intranasal neuropeptide Y, intranasal oxytocin, tianeptine oxalate, verucerfont), and emerging psychedelic interventions (ketamine, MDMA-assisted psychotherapy, psilocybin-assisted psychotherapy). The aim is to integrate these agents into pathophysiological frameworks of trauma-related disorders.
In veterans with PTSD, mindfulness-based stress reduction (MBSR) and present-centered group therapy both increased morning cortisol levels from baseline to 9 weeks, but the increase was significantly smaller with MBSR (mean difference 1.69 ± 0.8 SE). Changes in interleukin-6 and C-reactive protein did not differ between groups. Greater self-reported mindfulness was linked to higher cortisol and to reduced PTSD and depression severity. Higher IL-6 and CRP were associated with less severe PTSD but not depression. Pooled results confirmed MBSR outperformed the active control for clinical improvement. Increased mindfulness may recalibrate cortisol levels, suggesting a therapeutic response.
Both mindfulness-based stress reduction (MBSR) and present-centered group therapy (PCGT) led to significant improvement in PTSD symptoms among U.S. military veterans, as measured by the clinician-administered CAPS-IV scale, with no statistically significant difference between the two treatments. However, the MBSR group showed a statistically significant improvement in self-reported PTSD symptoms on the PTSD Checklist over the nine-week treatment period, though this difference was not maintained at the 16-week follow-up. The study involved 214 veterans randomly assigned to eight weeks of either 90-minute group MBSR or PCGT. Strengths include a large sample and multisite design; limitations include high attrition and low representation of women.