Pollack M H, Rapaport M H, Clary C M, Mardekian J, Wolkow R
Department of Psychiatry, Massachusetts General Hospital, Boston 02114-7541, USA.
J Clin Psychiatry. 2000 Dec;61(12):922-7.
More than one third of panic disorder patients have a chronic and/or recurrent form of the disorder, accounting for much of the individual and societal cost associated with the illness. Six clinical variables have been most consistently identified as high-risk predictors of poor outcome: (1) panic severity, (2) presence of agoraphobia, (3) comorbid depression, (4) comorbid personality disorder, (5) duration of illness, and (6) female sex. No published research has systematically examined the differential antipanic efficacy of selective serotonin reuptake inhibitors in patients at high risk for poor outcome.
Data were pooled (N = 664) from 4 double-blind, placebo-controlled studies of the efficacy of sertraline for the treatment of DSM-III-R panic disorder. Two of the studies were 12-week fixed-dose studies with starting daily doses of sertraline, 50 mg, and 2 were 10-week flexible-dose studies with starting daily doses of sertraline, 25 mg. All other study design features were the same, except for the exclusion of women of childbearing potential in the 2 fixed-dose studies. Exclusion of patients with marked personality disorders and depression meant that only 4 of the poor-outcome variables could be evaluated.
Clinical improvement was similar for patients treated with sertraline whether or not they carried an agoraphobia diagnosis, had a duration of illness > 2 years, or were female. Patients with high baseline panic severity had significantly (p = .01) less improvement on the endpoint Clinical Global Impressions-Improvement (CGI-I) scale than patients with moderate severity, although the Clinical Global Impressions-Severity of Illness scale change score was higher in the patients with high severity (-2.00 vs. -1.31). For patients with 3 or more high-risk variables, there was a modest, but statistically significant, tendency for reduced global improvement (endpoint CGI-I score of 2.7 for the high-risk vs. 2.4 for the non-high-risk group; p = .017), although the high-risk group actually had a similar endpoint reduction in frequency of panic attacks (82%) compared with the non-high-risk group (78%).
Treatment of panic disorder with sertraline was generally effective, even in the presence of baseline clinical variables that have been associated with poor treatment response. The main limitations of the analysis were the reliance on pooled data from 4 studies (even if the designs were similar) and our inability to examine the impact of depression and personality disorders on response to treatment because of the exclusion criteria of the clinical trials.
超过三分之一的惊恐障碍患者患有慢性和/或复发性疾病,这构成了与该疾病相关的大部分个人和社会成本。六个临床变量一直被最一致地确定为预后不良的高风险预测因素:(1)惊恐严重程度,(2)广场恐惧症的存在,(3)共病抑郁症,(4)共病人格障碍,(5)病程,以及(6)女性性别。尚无已发表的研究系统地检验选择性5-羟色胺再摄取抑制剂对预后不良高风险患者的不同抗惊恐疗效。
汇总了4项关于舍曲林治疗DSM-III-R惊恐障碍疗效的双盲、安慰剂对照研究的数据(N = 664)。其中2项研究为12周固定剂量研究,舍曲林起始日剂量为50 mg,另外2项为10周灵活剂量研究,舍曲林起始日剂量为25 mg。除2项固定剂量研究排除了有生育潜力的女性外,所有其他研究设计特征均相同。排除有明显人格障碍和抑郁症患者意味着只能评估4个预后不良变量。
无论是否诊断为广场恐惧症、病程是否>2年或是否为女性,接受舍曲林治疗的患者临床改善情况相似。基线惊恐严重程度高的患者在终点临床总体印象改善(CGI-I)量表上的改善明显(p = 0.01)少于中度严重程度的患者,尽管疾病严重程度临床总体印象量表变化评分在严重程度高的患者中更高(-2.00对-1.31)。对于有3个或更多高风险变量的患者,尽管高风险组与非高风险组相比,实际终点时惊恐发作频率的降低相似(82%对78%),但总体改善有适度但统计学上显著的降低趋势(高风险组终点CGI-I评分为2.7,非高风险组为2.4;p = 0.017)。
即使存在与治疗反应不佳相关的基线临床变量,舍曲林治疗惊恐障碍总体上仍有效。该分析的主要局限性在于依赖4项研究的汇总数据(即使设计相似),以及由于临床试验的排除标准,我们无法检验抑郁症和人格障碍对治疗反应的影响。