McGill University Health Centre, Allan Memorial Institute, Clinical Psychopharmacology Unit, Montreal, QC, Canada.
CNS Neurosci Ther. 2011 Dec;17(6):750-60. doi: 10.1111/j.1755-5949.2010.00210.x. Epub 2010 Nov 30.
Generic medications do not undergo the rigorous approval process required of original medications. Their effectiveness and safety is expected to be equal to that of their more expensive counterparts. However, several case reports and studies describe clinical deterioration and decreased tolerability with generic substitution. Pubmed was searched from January 1, 1974 to March 1, 2010. The MeSH term "generic, drugs" was combined with "anticonvulsants," "mood stabilizers," "lithium," "antidepressants," "antipsychotics," "anxiolytics," and "benzodiazepines." Additional articles were obtained by searching the bibliographies of relevant references. Articles in English, French, or Spanish were considered if they discussed clinical equivalence of generic and brand-name medications, generic substitution, or issues about effectiveness, tolerability, compliance, or economics encountered with generics. Clinical deterioration, adverse effects, and changes in pharmacokinetics are described with generic substitution of several anticonvulsants/mood stabilizers (carbamazepine, valproate, lamotrigine, gabapentin, topiramate, lithium), antidepressants (amitriptyline, nortriptyline, desipramine, fluoxetine, paroxetine, citalopram, sertraline, venlafaxine, mirtazapine, bupropion), antipsychotics (risperidone, clozapine), and anxiolytics (clonazepam, alprazolam). Generics do not always lead to the anticipated monetary savings and also raise compliance issues. Although the review is limited by publication bias and heterogeneity of the studies in the literature, we believe there is enough concern to advise generic switching on an individual basis with close monitoring throughout the transition. Health professionals should be aware of the stakes around generic substitution especially when health economics promote universal use of generics.
仿制药并未经过与原研药相同的严格审批流程。其有效性和安全性应该与原研药相当。然而,有几项病例报告和研究表明,仿制药替代后会出现临床恶化和耐受性降低的情况。我们检索了 1974 年 1 月 1 日至 2010 年 3 月 1 日的 PubMed 数据库,使用的主题词是“generic,drugs”,并结合了“anticonvulsants”、“mood stabilizers”、“lithium”、“antidepressants”、“antipsychotics”、“anxiolytics”和“benzodiazepines”。通过检索相关参考文献的书目,我们还找到了额外的文章。如果文章讨论了仿制药和品牌药的临床等效性、仿制药替代或与仿制药相关的有效性、耐受性、顺应性或经济性问题,我们也考虑纳入英文、法文或西班牙文的文章。我们描述了几种抗惊厥药/心境稳定剂(卡马西平、丙戊酸钠、拉莫三嗪、加巴喷丁、托吡酯、锂)、抗抑郁药(阿米替林、去甲替林、地昔帕明、氟西汀、帕罗西汀、西酞普兰、舍曲林、文拉法辛、米氮平、安非他酮)、抗精神病药(利培酮、氯氮平)和苯二氮䓬类药物(氯硝西泮、阿普唑仑)的仿制药替代后出现的临床恶化、不良反应和药代动力学改变。仿制药并不总能带来预期的节省成本效果,也会引发顺应性问题。尽管综述受到发表偏倚和文献中研究异质性的限制,但我们认为,考虑到这些问题,应该建议在个体化基础上进行仿制药转换,并在整个转换过程中进行密切监测。医疗保健专业人员应该意识到仿制药替代的风险,尤其是在健康经济学提倡普遍使用仿制药的情况下。