BOCA RATON, Florida (EGMN) – Patients with posttraumatic stress disorder permitted to choose either 10 weeks of prolonged exposure therapy or sertraline had better adherence and treatment response, compared with others randomly assigned to the intervention they did not want.

“Our results highlight a need to rethink a ‘one size fits all’ approach to the treatment of PTSD,” Norah C. Feeny, Ph.D., said during a late-breaking research session at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

“We are fortunate we have good, efficacious treatments for PTSD,” Dr. Feeny said. “But patient preference may affect efficacy down the line.”

In this first head-to-head comparison between a validated cognitive-behavioral therapy and a selective serotonin reuptake inhibitor for PTSD, 61% of 200 participants at baseline said they would prefer prolonged exposure. The remaining 39% indicated they would prefer treatment with sertraline.

Dr. Feeny was somewhat surprised by these percentages because “prolonged exposure requires them to engage with material they want to avoid, such as combat, a motor vehicle accident, or sexual assault. Sertraline does not require engagement with this painful stimuli,” said Dr. Feeny, director of the PTSD Treatment & Research Program at Case Western Reserve University in Cleveland. The NIMH and Pfizer, maker of Zoloft, funded the study. Zoloft is the brand name for sertraline.

A total of 97 participants were randomized to a “choice” group and 103 others to a “no choice” group. Therefore, some in the no-choice group received an intervention they did not want. This design allowed analysis of the degree to which patient preference affects treatment adherence and outcomes, Dr. Feeny said.

The prolonged exposure group received manualized therapy for 10 weekly sessions, each lasting 90-120 minutes. The sertraline group also received 10 weekly, 30-minute manualized education sessions (e.g., about common reactions to trauma).

“We know very little about how prolonged exposure and sertraline compare with each other,” Dr. Feeny said. Although overall there were no significant differences in treatment response (75% in the prolonged exposure group vs. 65% in the sertraline group), “prolonged exposure may have a slight advantage in terms of the magnitude of change [from baseline].”

Patient preference for treatment, however, did make a difference, Dr. Feeny said. After 10 weeks, “those who received their choice were doing better in terms of responder status.” Participants in the no-choice group randomized to the intervention they did not want, referred to as the “discrepancy” cohort, were more likely to have a lower response. “People in the discrepancy group were doing worse on every index.” For example, this group had lower adherence to their treatment – they were more likely to attend fewer sessions of prolonged exposure or took “substantially lower” doses of sertraline during the study.

All participants met DSM-IV criteria for chronic PTSD as their primary diagnosis and were aged 18-65 years (mean, 37 years). The cohort was primarily female, 76%. Most, 65%, were white, 22% were African American, and the remaining 13% identified with other ethnic groups. Participants were “quite chronic,” enrolling in the study a mean of 12 years after their trauma. The most common traumatic events were adult sexual assault (31%), childhood assault (24%), and adult nonsexual assault (23%). If patients were multiply traumatized, they were asked to choose a primary trauma in case they chose or were assigned to prolonged exposure.

Although patients could not be blinded in this or any behavioral versus medication protocol, raters were blinded to group assignment when interpreting the findings, Dr. Feeny said in response to a meeting attendee question. “In an attempt to be real-world, we were less concerned about blinding people to the interventions.”

Dr. Feeny explained why she and her colleagues chose a novel, double-randomized treatment preference study design. Beyond the obvious lack of choice for patients in traditional randomized controlled trial, “if we just let people choose their own medications, there could be selection bias,” she said. In an attempt to be as impartial as possible while allowing participants to make a more informed choice, they initially watched two videos. Each video featured clinicians who explained the rationale for each intervention, including efficacy information, procedures, and possible side effects. Wording of the two videos was matched as closely as possible.

Dr. Feeny only presented preliminary, intent-to-treat results of the 10-week Acute Treatment for Chronic PTSD study at the meeting. Two-year follow-up findings will be presented in the future, she added.

Dr. Feeny is a consultant or lecturer for multiple pharmaceutical companies, but none of her disclosures were relevant to this presentation.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

 

佛罗里达州博卡拉顿(EGMN)——与那些在随机分配中接受自己不想要治疗方式的患者相比，那些获准在为期10周的延长暴露治疗或舍曲林治疗之间进行自由选择的创伤后应激障碍(PTSD)患者的依从性及对治疗的反应性均更佳。

 

Norah C. Feeny博士在由美国国立精神卫生研究所(NIMH)赞助的临床新药评估机构会议上汇报最新研究进展时发言说道，“我们的研究结果强调，有必要对‘一刀切’式的 PTSD治疗方案进行重新思考”。

 

Feeny博士说：“我们有幸拥有针对PTSD的恰当且有效的治疗方案，但是患者的选择可能会影响到某一治疗环节的有效性。”

 

在这项研究中，研究者对PTSD治疗中所使用的一种有效的认知行为疗法和一种选择性5羟色胺再摄取抑制剂进行了首度直接对比，在基线时，61%的受试者说他们更愿意接受延长暴露治疗。余下的39%受试者表示他们更愿意接受舍曲林治疗。

 

克利夫兰市凯斯西储大学PTSD治疗与研究项目负责人Feeny博士对这一百分比略感惊讶，他说：“延长暴露治疗要求他们去面对那些他们希望回避的事物，比如一场争斗，一次机动车事故或性侵犯。接受舍曲林治疗则不需要接触这些令人痛苦的刺激因素”。

 

总计有97例受试者被随机分配至“选择”组，另外103例受试者则被分配至“无选择”组。因此，无选择组的某些受试者接受了一种他们并不想要的治疗方案。Feeny博士说，该研究设计使研究者得以就患者偏好对治疗依从性和临床转归的影响程度进行分析。

 

延长暴露治疗组的受试者接受了持续10周的行为治疗，每次治疗持续90~120 min。舍曲林组的受试者也接受了共计10周每周30 min的行为教育(例如，关于人们对创伤的常见反应)。

 

Feeny博士说：“我们对如何就延长暴露治疗和舍曲林治疗进行交互对比了解很少”。尽管总体来说，两种疗法在治疗反应率上并不存在显著差异(延长治疗组为75%对舍曲林组的65%)。“延长暴露可能在变化幅度方面稍占优势(从基线算起)。”

 

Feeny博士说，患者对治疗方式的偏好对结果确实构成了影响。在10周后，“那些接受自己选择的治疗方案的受试者在反应状态方面表现更好。”那些在随机分配中接受了自己不喜欢的治疗方案的非选择组受试者(他们被称为“不一致”队列)出现更低反应性的可能性更大。“不一致组的受试者在每项指标上均表现更差。”例如，该组受试者对治疗的依从性更差——他们更倾向于在研究期间减少延长暴露治疗的次数，或是服用“大幅降低”剂量的舍曲林。

 

所有受试者在初次诊断时均满足《精神障碍诊断统计手册》第四版(DSM-IV)中关于PTSD的诊断标准，且患者年龄介于18~65岁(平均37岁)。该队列主要由女性构成，占全部受试者的76%。其中大部分(65%)是白种人，22%是非洲裔美国人，其余13%经确认属于其他种族。受试者均患有 “相当显著的慢性疾病”，截至被招募入该研究时，这些受试者创伤事件的平均发生时间为12年。最常见的创伤事件是性侵犯(31%)、童年时受到虐待(24%)和与性无关的成年期伤害(23%)。如果患者曾受到多种创伤，且他们选择或被分配接受延长暴露治疗，则研究者会要求他们选择其中一项作为最主要创伤事件。

 

Feeny博士就某位与会者的问题回答说，尽管这项研究或其他任意一项行为——药物治疗对比研究中对患者的安排均不符合盲法要求，但评估者在对研究结果进行解释时遵循了盲法。“为了保证研究的真实性，我们较少关注受试者在接受治疗时是否符合盲法要求。”

 

Feeny博士就她及其同事为何在此项治疗偏好研究中选择新型、双随机的设计方案进行了解释。传统的随机对照试验除了存在患者缺乏选择权这一明显的缺点外，“如果我们仅安排患者自行选择治疗方案，那么便可能存在选择偏倚，”她说。在确保患者拥有更多知情选择权的同时，我们还试图做到尽可能公正，患者在治疗的初始阶段观看了两盘录像带。每盘录像带中均含有临床医生对每种治疗方案基本原理进行讲解的内容，其中包括该治疗的疗效信息、治疗流程和可能存在的不良反应。且两盘录像带中的相关用语措词保持了最高程度的一致性。

 

Feeny博士仅提交了针对慢性PTSD患者的10周急性治疗的初步意向性治疗结果。她补充说,研究者在未来还将公布2年随访调查的研究结果。

 

Feeny博士目前担任多家制药公司的顾问或讲师，但她所披露的各项情况均与该报告无关。

 

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