Pelissolo A
Service de psychiatrie adulte et CNRS centre Emotion, groupe hospitalier de la Pitié-Salpêtrière, AP-HP, 47, boulevard de l'Hôpital, 75013 Paris, France.
Encephale. 2008 Sep;34(4):400-8. doi: 10.1016/j.encep.2008.04.004. Epub 2008 Aug 15.
Anxiety disorders are highly prevalent and disabling disorders, for which selective serotonin reuptake inhibitor (SSRI) antidepressants are an effective treatment. Escitalopram is the most selective SSRI available. Beyond its well-established efficacy in depression with or without anxiety, preclinical studies have demonstrated that escitalopram has a broad spectrum of anxiolytic activity.
This review focuses on the therapeutic use and the tolerability issues of escitalopram in the treatment of adult patients with panic disorder, generalized anxiety disorder (GAD), social anxiety disorder, and obsessive-compulsive disorder (OCD), on the basis of numerous recent short-term and long-term controlled studies in these disorders. In a 10-week randomised, double-blind trial in patients with panic disorder, escitalopram (flexible doses 5-10 mg/d) was significantly more effective than placebo in reducing the panic attack frequency, with a faster onset of action than citalopram. Fifty percent of escitalopram recipients and 38% of placebo recipients experienced no panic attacks, with a similar incidence of the most common adverse events for both groups. LITERATURE FINDINGS IN PD: In an open-label study in elderly (>65 years) patients with panic disorder, improvement in panic attack frequency and secondary efficacy variables occurred more rapidly in escitalopram than citalopram recipients. LITERATURE FINDINGS IN GAD: In four double-blind, comparative, eight- to 12-week studies in patients with GAD, escitalopram was more effective than placebo and at least as effective as paroxetine in reducing the mean Hamilton Rating Scale for Anxiety total score. Escitalopram 10-20 mg/d demonstrated continued efficacy in a 24-week extension study of short double-blind trials and in a placebo-controlled, double-blind, 24/76-week relapse-prevention study. In this trial, escitalopram recipients showed a significantly longer time to relapse and reduced risk of relapse than placebo recipients, and the risk of relapse was 4.04 times higher in the placebo group than in the escitalopram group. Escitalopram was well tolerated and only 7% patients withdrew, due to adverse events in the escitalopram group, versus 8% in the placebo group. LITERATURE FINDINGS IN SOCIAL PHOBIA: In two randomised, double-blind, 12- and 24-week studies in patients with social anxiety disorder (social phobia), escitalopram 10-20 mg/d was generally more effective than placebo and at least as effective as paroxetine in reducing the mean Liebowitz Social Anxiety Scale total scores. In a 24-week double-blind, placebo-controlled relapse-prevention study, escitalopram recipients had a longer time to relapse and reduced risk of relapse compared with placebo recipients, and significantly fewer escitalopram than placebo recipients relapsed (22% versus 50%). In these studies, the treatment effects of escitalopram were independent of gender, symptom severity and chronicity, and comorbid depressive symptoms, and the drug was tolerated well. LITERATURE FINDINGS IN OCD: Finally, in patients with OCD, escitalopram 20mg/d for 12 weeks was more effective than placebo, and at least as effective as paroxetine 40 mg/day, with respect to a mean reduction from baseline in the Yale-Brown Obsessive Scale total score. In a 24-week, randomised, placebo-controlled relapse-prevention study, the proportion of patients who relapsed in the escitalopram group (23%) was 2.74 times lower than in the placebo group (52%). In both groups, the majority of adverse events reported were mild to moderate.
On the whole, numerous clinical data indicate that escitalopram, 10-20 mg/d, is an effective and well-tolerated first-line treatment option for the management of panic disorder, GAD, social anxiety and OCD. Beyond short-term demonstrations of efficacy in these disorders, several controlled relapse-prevention studies showed the necessity and utility of maintaining the treatment six months or more after the remission has been obtained.
焦虑症是高度流行且使人致残的疾病,选择性5-羟色胺再摄取抑制剂(SSRI)类抗抑郁药是其有效的治疗药物。艾司西酞普兰是现有的选择性最强的SSRI。除了在伴或不伴焦虑的抑郁症中已确立的疗效外,临床前研究表明艾司西酞普兰具有广泛的抗焦虑活性。
本综述基于近期在这些疾病中进行的大量短期和长期对照研究,重点关注艾司西酞普兰在治疗成人惊恐障碍、广泛性焦虑症(GAD)、社交焦虑症和强迫症(OCD)中的治疗用途和耐受性问题。在一项针对惊恐障碍患者的为期10周的随机双盲试验中,艾司西酞普兰(灵活剂量5-10毫克/天)在降低惊恐发作频率方面显著优于安慰剂,起效比西酞普兰更快。50%接受艾司西酞普兰治疗的患者和38%接受安慰剂治疗的患者未出现惊恐发作,两组最常见不良事件的发生率相似。惊恐障碍的文献研究结果:在一项针对老年(>65岁)惊恐障碍患者的开放标签研究中,与接受西酞普兰治疗的患者相比,接受艾司西酞普兰治疗的患者惊恐发作频率和次要疗效变量的改善出现得更快。广泛性焦虑症的文献研究结果:在四项针对广泛性焦虑症患者的双盲、对照、为期8至12周的研究中,艾司西酞普兰在降低汉密尔顿焦虑量表总分均值方面比安慰剂更有效,且至少与帕罗西汀一样有效。在短期双盲试验的一项为期24周的延长期研究以及一项安慰剂对照、双盲、24/76周预防复发研究中,10-20毫克/天的艾司西酞普兰显示出持续疗效。在该试验中,与接受安慰剂治疗的患者相比,接受艾司西酞普兰治疗的患者复发时间显著更长,复发风险降低,安慰剂组的复发风险比艾司西酞普兰组高4.04倍。艾司西酞普兰耐受性良好,艾司西酞普兰组仅有7%的患者因不良事件退出,而安慰剂组为8%。社交恐惧症的文献研究结果:在两项针对社交焦虑症(社交恐惧症)患者的随机双盲、为期12周和24周的研究中,10-20毫克/天的艾司西酞普兰在降低利伯维茨社交焦虑量表总分均值方面通常比安慰剂更有效,且至少与帕罗西汀一样有效。在一项为期24周的双盲、安慰剂对照预防复发研究中,与接受安慰剂治疗的患者相比,接受艾司西酞普兰治疗的患者复发时间更长,复发风险降低,且复发的艾司西酞普兰治疗患者明显少于安慰剂治疗患者(22%对50%)。在这些研究中,艾司西酞普兰的治疗效果与性别、症状严重程度和慢性病程以及共病抑郁症状无关,且该药物耐受性良好。强迫症的文献研究结果:最后,在强迫症患者中,20毫克/天的艾司西酞普兰治疗12周在降低耶鲁-布朗强迫量表总分均值方面比安慰剂更有效,且至少与40毫克/天的帕罗西汀一样有效。在一项为期24周的随机、安慰剂对照预防复发研究中,艾司西酞普兰组复发患者的比例(23%)比安慰剂组(52%)低2.74倍。两组报告的大多数不良事件均为轻至中度。
总体而言,大量临床数据表明,10-20毫克/天的艾司西酞普兰是治疗惊恐障碍、广泛性焦虑症、社交焦虑症和强迫症的有效且耐受性良好的一线治疗选择。除了在这些疾病中的短期疗效证明外,多项对照预防复发研究表明,在获得缓解后维持治疗六个月或更长时间是必要且有用的。