VIENNA (EGMN) – Routine prophylaxis with escitalopram slashed the risk of developing clinically relevant depression by 69% during 6-12 months of interferon-based antiviral therapy in patients with chronic hepatitis C infection.

Based upon this impressive finding in a double-blind, randomized, multicenter, phase III clinical trial, preemptive escitalopram (Lexapro) can be recommended for all patients starting long-term treatment with pegylated interferon-alpha and ribavirin, the current standard for chronic hepatitis C, Dr. Martin Schaefer declared at the annual International Liver Congress sponsored by the European Association for the Study of the Liver.

In a logistic regression analysis, prophylactic escitalopram was independently associated with a 69% reduction in the risk of interferon-associated depression. Depression is one of the most common complications of interferon therapy. Prior studies have established that 20%-40% of patients with chronic hepatitis C virus (HCV) infection develop treatment-related major depression, with resultant diminished quality of life and disruptions to treatment adherence.

Mild to moderate depressive symptoms affect 60%-70% of interferon-treated patients with no prior psychiatric history, added Dr. Schaefer, head of the department of psychiatry, psychotherapy, and addiction medicine at Essen (Germany) Medical Center.

He reported on 208 patients with chronic HCV infection and no previous psychiatric history. During a 12-week baseline period prior to starting 6 or 12 months of pegylated interferon-alpha-2a plus ribavirin, all patients were evaluated to confirm that they had no psychiatric disorders at baseline.

Two weeks before the start of antiviral therapy, patients were randomized in a double-blind manner to begin taking either placebo or escitalopram 10 mg as a single daily morning dose for the duration of their anti-HCV therapy. Psychiatric assessments, including evaluation of mood changes using the Montgomery-Åsberg Depression Scale (MADRS), were performed at baseline and weeks 2, 4, 12, 24, 48, and 72.

Clinically relevant depression, as defined by a MADRS score of 13 or more, occurred in 27% of patients on escitalopram and 53% of those on placebo. Mild or greater depression – defined as a MADRS score of 10 or more – during interferon treatment had a prevalence of 41% with escitalopram, compared with 63% in controls.

The highest prevalence at any single time point was seen at week 12, when 26.7% of controls had clinically relevant depression, compared with 10% of the escitalopram group, the psychiatrist continued.

MADRS scores were significantly lower in the escitalopram arm at each assessment. For example, at week 48, the mean MADRS score was 5.0 in the escitalopram group, compared with 9.3 in controls.

Finally, severe depression, as evidenced by a MADRS score of 25 or more, occurred in 12% of controls and 1% of patients on the prophylactic antidepressant.

There was no evidence that the antidepressant blunted the effectiveness of the HCV therapy. A sustained virologic response was achieved in 55.6% of the escitalopram group and 46.2% on placebo, a nonsignificant difference.

Side effects of HCV treatment were significantly less common in the escitalopram group. Particularly notable was a sharp reduction in complaints of fatigue and insomnia, compared with the control group’s experience.

Dr. Schaefer noted that since only 53% of study participants on placebo developed clinically relevant depression, across-the-board use of the preemptive escitalopram strategy means that nearly half of all patients would not actually benefit from the antidepressant. However, prophylaxis could be used selectively, focusing on higher-risk subgroups. These include women, patients over age 30 years, those with a baseline MADRS of more than 5, and patients with a history of depression, he said.

The phase III trial, known by the German acronym CIPPAD, was funded by Hoffmann–La Roche Ltd. Dr. Schaefer disclosed serving as a consultant to the pharmaceutical company.

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

维也纳(EGMN) ——慢性丙型肝炎患者在6~12个月的以干扰素为基础的抗病毒治疗期间，采用西酞普兰常规预防可使治疗相关抑郁发生的风险大幅降低69%。

 

一项双盲、随机、多中心、III期临床试验得出的结果令人印象深刻，据此，Martin Schaefer博士在由欧洲肝病学会主办的本年度国际肝脏会议上宣布，聚乙二醇α-干扰素和利巴韦林是目前治疗慢性丙型肝炎的标准疗法，建议开始该疗法长期治疗的所有患者采用预防性西酞普兰(Lexapro)。

 

在Logistic回归分析中，单独使用预防性西酞普兰可使干扰素相关抑郁风险降低69%。抑郁是干扰素治疗最常见的并发症。以往研究显示，20%~40%的慢性丙型肝炎病毒(HCV)感染患者可发生治疗相关的抑郁症，从而降低生活质量，破坏治疗依从性。

 

轻至中度抑郁症状会影响60%~70%无精神病史的干扰素治疗患者，Essen(德国)医学中心精神病学、心理疗法和药物成瘾科的主任 Schaefer博士补充说。

 

他报告了208名既往无精神病史的慢性HCV感染患者。在采用聚乙二醇α-2a干扰素联合利巴韦林进行6或12个月治疗之前，在为期12周的基线期对所有患者进行评价，以确定他们在基线时没有精神障碍。

 

开始抗病毒治疗前2周以及抗HCV治疗期间，患者开始随机双盲服用安慰剂或西酞普兰10 mg，每日清晨服用1次。在基线、第2、4、12、24、48和72周时采用Montgomery-Åsberg抑郁量表(MADRS)进行精神评估，包括评价情绪变化。

 

治疗相关抑郁，定义为MADRS评分13分或更高，出现于27%服用西酞普兰的患者和53%服用安慰剂的患者。在干扰素治疗期间，41%服用西酞普兰的患者出现轻度或更重的抑郁——定义为MADRS评分10分或更高，而对照组为63%。

 

单个时间点的最高患病率出现在第12周时，26.7%的对照患者出现治疗相关抑郁，而西酞普兰组为10%，精神病学家继续说。

 

在每个评估点，西酞普兰组的MADRS评分显著低于对照组。例如，在第48周，西酞普兰组的MADRS平均评分为5.0，而对照组为9.3。

 

最后，严重抑郁，定义为MADRS评分25分或更高，出现在12%的对照患者和1%采用预防性抗抑郁治疗的患者。

 

抗抑郁治疗不会降低HCV治疗的疗效。西酞普兰组55.6%的患者和安慰剂组46.2%的患者获得持续性病毒学应答，两组没有显著差异。

 

西酞普兰组HCV治疗的不良反应显著降低。尤其需要指出的是，与对照组相比，主诉乏力和失眠的患者比例显著降低。

 

Schaefer博士指出，由于安慰剂组只有53%的受试者出现治疗相关抑郁，预防性全面应用西酞普兰意味着几乎半数的患者不会从抗抑郁治疗中受益。然而，应该选择性预防用药，主要用于高风险的亚组患者。这包括女性、年龄>30岁的患者、基线MADRS>5分者，以及有抑郁病史的患者，他说。

 

这项III期临床试验，被称CIPPAD(德语首字母缩略词)，由罗氏公司资助。Schaefer博士为该制药公司的顾问。

 

爱思唯尔  版权所有