Westenberg H G
Department of Biological Psychiatry, University Hospital Utrecht, The Netherlands.
J Affect Disord. 1996 Sep 9;40(1-2):85-93. doi: 10.1016/0165-0327(96)00043-2.
Panic disorder is becoming better recognised and understood as a chronic, debilitating but treatable condition. Drug treatment options shown by adequate research to be beneficial in this condition include mainly the benzodiazepine alprazolam, the tricyclic antidepressants (TCAs) imipramine and clomipramine, the monoamine oxidase inhibitor (MAOI) phenelzine, and the newer selective serotonin reuptake inhibitors (SSRIs) fluvoxamine and paroxetine. Alprazolam, although approved for use in panic disorder in the US and very widely used, is associated with a risk of dependence and withdrawal syndromes. Given that depression frequently occurs as a comorbid condition with panic disorder the use of antidepressants is a logical choice. Among the antidepressants, MAOIs are little-used in panic disorder, mainly because of their potential for precipitating hypertensive crises if tyramine is ingested. TCAs are widely used and are effective but they are associated with initial activation, or 'jitteriness', have a 4-6-week time lag before onset of beneficial effect and produce troublesome side effects in a high proportion of patients, particularly during long-term use. TCAs are also cardiotoxic in overdosage, and panic disorder patients with comorbid depression are at high risk of attempted suicide. Serotonin dysregulation has been implicated in the pathogenesis of anxiety disorders in general, and panic disorder in particular. Among the TCAs, those with an effect on serotonin reuptake are most effective in panic disorder. SSRIs are specifically active on serotonin reuptake and do not have anticholinergic effects or act on the noradrenergic system. There is a clear pharmacological rationale for believing that SSRIs should be as effective as TCAs in panic disorder and better tolerated. Accumulating clinical research evidence supports this hypothesis. Further comparative studies with standard agents and additional long-term studies to support the initial long-term data with paroxetine are needed to confirm SSRIs as drug treatment of choice in panic disorder.
惊恐障碍正日益被视为一种慢性、使人衰弱但可治疗的疾病，人们对它的认识和理解也在不断加深。经充分研究表明，对这种疾病有益的药物治疗选择主要包括苯二氮䓬类药物阿普唑仑、三环类抗抑郁药丙咪嗪和氯米帕明、单胺氧化酶抑制剂（MAOI）苯乙肼，以及较新的选择性5-羟色胺再摄取抑制剂（SSRI）氟伏沙明和帕罗西汀。阿普唑仑虽在美国被批准用于治疗惊恐障碍且使用广泛，但存在依赖和戒断综合征风险。鉴于抑郁症常与惊恐障碍并发，使用抗抑郁药是合理选择。在抗抑郁药中，MAOI在惊恐障碍中很少使用，主要是因为如果摄入酪胺，它们有引发高血压危象的可能性。三环类抗抑郁药使用广泛且有效，但它们会引发初始激活或“神经过敏”，在产生有益效果前有4至6周的时间滞后，并且在很大一部分患者中会产生令人烦恼的副作用，尤其是在长期使用期间。三环类抗抑郁药过量服用时也具有心脏毒性，而伴有抑郁症的惊恐障碍患者有很高的自杀企图风险。一般来说，血清素失调与焦虑症的发病机制有关，尤其是惊恐障碍。在三环类抗抑郁药中，那些对血清素再摄取有作用的药物在惊恐障碍中最有效。SSRI对血清素再摄取有特异性作用，没有抗胆碱能作用，也不作用于去甲肾上腺素能系统。有明确的药理学依据认为，SSRI在惊恐障碍中应与三环类抗抑郁药一样有效且耐受性更好。越来越多的临床研究证据支持这一假设。需要进一步与标准药物进行比较研究，并开展更多长期研究以支持帕罗西汀的初始长期数据，从而确认SSRI作为惊恐障碍药物治疗的首选。
