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For many antidepressants, the issue of brand-name versus generic has no practical significance. Elavil was first marketed almost a half century ago, and its patent has long expired. It lives on, however, but as generic amitriptyline(Drug information on amitriptyline). Today, only a few antidepressants are still fully protected by patents, namely, Cymbalta (2010), Lexapro (2012), and Pristiq (2022) for major depressive disorder (MDD); and Seroquel (2011) and Symbyax (2017) for bipolar depression.
The issue of brand-name versus generic, however, is far more complex than merely listing patent expiration dates. Patents can be extended, challenged, and infringed on; financial considerations are enormous; and patient care issues are often of central importance. To place antidepressants in proper perspective, it is first necessary to provide some general background about patents and drug regulation.
Our patent system had its birth in the United States Constitution, which gave Congress power “To promote the Progress of Science and useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries” (US Constitution, Article 1, Section 8, Clause 8). Shortly thereafter, the US Patent and Trademark Office came into existence.1
Meanwhile, regulation and oversight of pharmaceuticals was evolving (Table 1)—particularly with the passage of the Pure Food and Drug Act of 1906 (the Wiley Act), which imposed standards for strength and purity and prohibited misbranding and adulteration. Its administration was in the hands of the Bureau of Chemistry, which changed its name in 1927 to the Food, Drug, and Insecticide Administration and in 1930 to the familiar Food and Drug Administration (FDA).2 It was not until 1938, following the debacle (many deaths from renal and hepatic toxicity) of Elixir Sulfanilamide(Drug information on sulfanilamide), that the Federal Food, Drug, and Cosmetic Act was passed that required proof of safety before a drug could be marketed. The Kefauver-Harris Amendment in 1962 required that a drug also show premarketing proof of efficacy. From then until 1984, both generic and brand-name manufacturers were required to show proof of efficacy and safety to receive FDA marketing approval.
The Drug Price Competition and Patent Term Restoration Act of 1984 (the Hatch-Waxman Act) greatly eased the entry of generics into the market by allowing the efficacy and safety of the original (branded) drug to apply to the generic and by only requiring the establishment of bio-equivalence for the generic.3 The Act also allowed generic drug companies to do bioequivalency testing and seek FDA approval before the expiration of the brand-name patent, thus allowing a rapid launch when the patent did expire.4
Patents were initially granted for 17 years, but this was extended to 20 years in 1995. The Hatch-Waxman Act recognized that with pharmaceuticals, the time from patent filing to FDA approval could take many years, which limited the time a company had to recoup its substantial investment and return profit to its investors. Consequently, a patent could be extended for up to 5 years to make up for time lost in the pipeline.5
Companies go to considerable lengths to protect the patents of their successful drugs, and generic drug companies go to considerable lengths to minimize the impact of such patents.6 One example was that the Act allowed 30-month stays of approval if the brand-name companies filed patent infringement suits against the generic companies. Apparently, the manufacturers of Paxil were able to extend its marketing exclusivity by 65 months by initiating several different patent disputes (the Medicare Modernization Act of 2003 restricted the stay to a single 30-month period).7
As one might imagine, having a period of generic exclusivity would allow a company to undercut the brand-name drug in price yet still reap substantial financial benefit. The Hatch-Waxman Act contained a 180-day exclusivity provision to reward the first generic company (sometimes more than one) that challenges a patent as not being valid or shows that there will be no patent infringement by its generic product. Even this absolute exclusivity can be foiled if the brand manufacturer provides a license to another generic company to manufacture its version of the drug.6 This, too, is an area of much controversy and contention.8 Once the 180 days have passed, the floodgates open and prices of generics are likely to tumble dramatically.