Yehuda Rachel, Bierer Linda M, Pratchett Laura C, Lehrner Amy, Koch Erin C, Van Manen Jaklyn A, Flory Janine D, Makotkine Iouri, Hildebrandt Tom
James J. Peters Veterans Affairs Medical Center, Bronx, New York, United States; Traumatic Stress Studies Division, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
James J. Peters Veterans Affairs Medical Center, Bronx, New York, United States; Traumatic Stress Studies Division, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Psychoneuroendocrinology. 2015 Jan;51:589-97. doi: 10.1016/j.psyneuen.2014.08.004. Epub 2014 Aug 13.
Prolonged exposure (PE) therapy for post-traumatic stress disorder (PTSD) in military veterans has established efficacy, but is ineffective for a substantial number of patients. PE is also associated with high dropout rates. We hypothesized that hydrocortisone augmentation would enhance symptom improvement and reduce drop-out rates by diminishing the distressing effects of traumatic memories retrieved during imaginal exposure. We also hypothesized that in responders, hydrocortisone augmentation would be more effective in reversing glucocorticoid indices associated with PTSD than placebo augmentation.
Twenty-four veterans were randomized to receive either 30 mg oral hydrocortisone or placebo prior to PE sessions 3-10 in a double-blind protocol. Glucocorticoid receptor sensitivity was assessed in cultured peripheral blood mononuclear cells (PBMC) using the in vitro lysozyme inhibition test and was determined before and after treatment. Intent-to-treat analysis was performed using latent growth curve modeling of treatment effects on change in PTSD severity over time. Veterans who no longer met diagnostic criteria for PTSD at post-treatment were designated as responders.
Veterans randomized to hydrocortisone or placebo augmentation did not differ significantly in clinical severity or glucocorticoid sensitivity at pre-treatment. Hydrocortisone augmentation was associated with greater reduction in total PTSD symptoms compared to placebo, a finding that was explained by significantly greater patient retention in the hydrocortisone augmentation condition. A significant treatment condition by responder status interaction for glucocorticoid sensitivity indicated that responders to hydrocortisone augmentation had the highest pre-treatment glucocorticoid sensitivity (lowest lysozyme IC50-DEX) that diminished over the course of treatment. There was a significant association between decline in glucocorticoid responsiveness and improvement in PTSD symptoms among hydrocortisone recipients.
The results of this pilot study suggest that hydrocortisone augmentation of PE may result in greater retention in treatment and thereby promote PTSD symptom improvement. Further, the results suggest that particularly elevated glucocorticoid responsiveness at pre-treatment may identify veterans likely to respond to PE combined with an intervention that targets glucocorticoid sensitivity. Confirmation of these findings will suggest that pharmacologic interventions that target PTSD-associated glucocorticoid dysregulation may be particularly helpful in promoting a positive clinical response to PTSD psychotherapy.
延长暴露（PE）疗法对退伍军人创伤后应激障碍（PTSD）具有已确立的疗效，但对相当一部分患者无效。PE还与高脱落率相关。我们假设氢化可的松增效可通过减轻想象暴露期间检索到的创伤性记忆的痛苦影响来增强症状改善并降低脱落率。我们还假设，在有反应者中，氢化可的松增效在逆转与PTSD相关的糖皮质激素指标方面比安慰剂增效更有效。
24名退伍军人在双盲方案中被随机分配，在第3至10次PE治疗前接受30mg口服氢化可的松或安慰剂。使用体外溶菌酶抑制试验在培养的外周血单核细胞（PBMC）中评估糖皮质激素受体敏感性，并在治疗前后进行测定。使用对PTSD严重程度随时间变化的治疗效果的潜在生长曲线模型进行意向性治疗分析。在治疗后不再符合PTSD诊断标准的退伍军人被指定为有反应者。
随机接受氢化可的松或安慰剂增效的退伍军人在治疗前的临床严重程度或糖皮质激素敏感性方面没有显著差异。与安慰剂相比，氢化可的松增效与PTSD总症状的更大减轻相关，这一发现可以通过氢化可的松增效组中显著更高的患者留存率来解释。糖皮质激素敏感性的显著治疗条件与反应者状态相互作用表明，氢化可的松增效的反应者在治疗前具有最高的糖皮质激素敏感性（最低溶菌酶IC50-DEX），且在治疗过程中降低。在氢化可的松接受者中，糖皮质激素反应性下降与PTSD症状改善之间存在显著关联。
这项初步研究的结果表明，氢化可的松增效的PE可能导致治疗留存率更高，从而促进PTSD症状改善。此外，结果表明，治疗前糖皮质激素反应性特别升高可能识别出可能对PE联合针对糖皮质激素敏感性的干预有反应的退伍军人。这些发现的证实将表明，针对与PTSD相关的糖皮质激素失调的药物干预可能在促进对PTSD心理治疗的积极临床反应方面特别有帮助。
