Dechant K L, Clissold S P
Adis Drug Information Services, Auckland, New Zealand.
Drugs. 1991 Feb;41(2):225-53. doi: 10.2165/00003495-199141020-00007.
Paroxetine is a potent and selective inhibitor of the neuronal reuptake of serotonin, thereby facilitating serotoninergic transmission; this action appears to account for the antidepressant activity observed with this drug. A mean terminal elimination half-life of approximately 24 hours permits once daily administration. Results of short term clinical trials have shown paroxetine to be significantly superior to placebo, and comparable to amitriptyline, clomipramine, imipramine, dothiepin and mianserin in relieving symptoms associated with major depressive disorders. Paroxetine has shown some preliminary promise in the treatment of depressive illness resistant to tricyclic antidepressant therapy but further studies are required before any conclusions can be drawn. Paroxetine in therapeutic doses has been very well tolerated, and the favourable tolerability profile of this agent appears to be its primary advantage over traditional antidepressant agents. Paroxetine causes minimal anticholinergic-type adverse effects, and unlike tricyclic antidepressants, it does not precipitate cardiovascular effects or provoke cardiac conduction disturbances. Nausea has been the most frequently reported adverse event during short term use of paroxetine, but it is generally mild and transient and subsides with continued use. With longer term use headache, sweating and constipation were the most frequently reported side effects but the incidence rate was not significantly different from that noted for comparator antidepressants. Furthermore, the frequency of withdrawal due to adverse effects is less with paroxetine than with tricyclic antidepressant agents. Overall, available data appear to indicate that while the efficacy of paroxetine is similar to that of traditional antidepressant drugs, the newer agent possesses much improved tolerability. In addition, the wide therapeutic index of paroxetine may be beneficial when treating patients with an increased risk of suicide. Thus, paroxetine clearly looks to become a valuable addition to the range of drugs currently available to treat depressive illness. Future research may help to further define the relative place of this newer agent in antidepressant therapy and determine how its overall therapeutic efficacy compares with that of other related antidepressant agents such as fluoxetine.
帕罗西汀是一种强效且具有选择性的5-羟色胺神经元再摄取抑制剂，从而促进5-羟色胺能传递；这一作用似乎可以解释该药物所观察到的抗抑郁活性。其平均终末消除半衰期约为24小时，允许每日给药一次。短期临床试验结果表明，帕罗西汀在缓解与重度抑郁症相关的症状方面显著优于安慰剂，且与阿米替林、氯米帕明、丙咪嗪、多塞平和米安色林相当。帕罗西汀在治疗对三环类抗抑郁药治疗耐药的抑郁症方面已显示出一些初步前景，但在得出任何结论之前还需要进一步研究。治疗剂量的帕罗西汀耐受性良好，该药物良好的耐受性似乎是其相对于传统抗抑郁药的主要优势。帕罗西汀引起的抗胆碱能类不良反应极小，与三环类抗抑郁药不同，它不会引发心血管效应或引起心脏传导紊乱。恶心是帕罗西汀短期使用期间最常报告的不良事件，但通常较轻且为一过性，持续用药后会消退。长期使用时，头痛、出汗和便秘是最常报告的副作用，但发生率与对照抗抑郁药相比无显著差异。此外，与三环类抗抑郁药相比，帕罗西汀因不良反应导致停药的频率更低。总体而言，现有数据似乎表明，虽然帕罗西汀的疗效与传统抗抑郁药相似，但这种新药的耐受性有了很大改善。此外，帕罗西汀较宽的治疗指数在治疗自杀风险增加的患者时可能有益。因此，帕罗西汀显然有望成为目前可用于治疗抑郁症的药物种类中的一种有价值的补充药物。未来的研究可能有助于进一步明确这种新药在抗抑郁治疗中的相对地位，并确定其总体治疗效果与其他相关抗抑郁药（如氟西汀）相比如何。
