Antidepressants: Brand Name or Generic?
By James W. Jefferson, MD |
May 12, 2009
Dr Jefferson is clinical professor of psychiatry at the University of Wisconsin School of Medicine and Public Health in Madison and a distinguished senior scientist at the Madison Institute of Medicine, Inc, in Middleton, Wis. The author reports that he has received grant/research support from BMS, Glaxo-
SmithKline, Lilly, Novartis, Pfizer, and Wyeth; he is a consultant for GlaxoSmithKline; he has received honoraria for lectures from BMS, GlaxoSmithKline, Lilly, and Wyeth; he holds stock in BMS, GlaxoSmithKline, and SciClone; he is a principal in Healthcare Technology Systems, Inc; and he has received other financial or material support from the companies listed above.
The FDA suggested that the reports of switch problems “are far more likely to be a consequence of the natural course of treated MDD than of the small pharmacokinetic differences between the generic and branded product.” Consequently, the FDA reaffirmed that it considers “the generic form of bupropion XL 300 mg bioequivalent and therapeutically equivalent to Wellbutrin XL 300 mg.”
Later that year, an article published in The Medical Letter concluded: “There is no acceptable evidence that Budeprion XL or any other generic formulation of bupropion is less effective or less safe than any corresponding formulation of Wellbutrin.”25 It also stated that absent a double-blind trial, testing the 300-mg formulations in volunteers “might be helpful.”
The saga continued into the summer of 2008, when Joe Graedon, cofounder of People’s Pharmacy, and others met with senior officials at the FDA Center for Drug Evaluation and Research.26 There was agreement that a study could be done that would compare both versions of the 300-mg XL products in patients who had experienced problems. Apparently, the FDA is designing a crossover protocol, but nothing definitive has appeared to date (J. Graedon, oral communication, January 22, 2009). Mean-while, the FDA continues to support its April 2008 decision.
Where does all of the brand-name versus generic brouhaha leave the clinician and the patient? One cannot conclude simply that brand-name drugs are good (and expensive) and generics are bad (and inexpensive). Had the Hatch-Waxman Act not eliminated the need for generic drug manufacturers to do the same efficacy and safety testing as branded drug manufacturers, there would be far, far fewer generics on the market (and at substantially higher prices). It is clear that when generics appear, the intensive and extensive marketing of the branded equivalent disappears as the revenue stream atrophies. Insurance programs and restrictive formularies will continue to direct clinicians toward generic prescribing. Few patients will want to bear the cost of a brand-name drug when a less expensive generic is available, especially patients with an illness such as depression that usually requires long-term treatment.
This may be an oversimplification, but it would seem reasonable for an FDA-approved generic of a brand-name drug to be preferred for patients who have not previously taken that chemical entity. Of greater potential concern are patients whose therapy is switched from a branded drug to its generic equivalent. It is difficult to estimate how much of a concern this would be. Case reports of problems, particularly those that are well substantiated because of differences in bioequivalence, are dwarfed by the number of patients who have a trouble-free transition. Of course, there are exceptions, and transition back to the original drug is quite reasonable and should be allowed in a way that does not penalize the patient financially.
Meeting FDA requirements for therapeutic equivalence should not be viewed as being synonymous with therapeutic identicalness (the same should also apply when switching among generics). In addition, it is impossible to ensure the quality of all generics at all times, so one must always remain open to the possibility of substitution mischief.
Patient education should do much to allay anxieties that otherwise might accompany an unannounced switch that could confuse a patient confronted with a pill of different size, shape, and scoring. Should problems still occur in the well-educated patient, alternative explanations for the problem should be excluded before re-prescribing the original drug.
Finally, this article does not address the far thornier issue of therapeutic substitution by which a pharmacist might replace a prescribed drug with a chemically different drug from within the same therapeutic category (eg, fluoxetine(Drug information on fluoxetine) for bupropion). Very strong arguments can be made against such a practice when dealing with antidepressants (and other medications).
The prescription of a specific medication is the result of a complex decision process involving clinician and patient after careful attention to numerous factors, including efficacy, adverse effects, drug interactions, and comorbid conditions. Absent the fully informed consent of the prescriber, therapeutic substitution is a potentially dangerous practice that should be vigorously discouraged.
Drugs Mentioned in This Article
Bupropion (Budeprion, Wellbutrin)
Fluoxetine (Prozac, Sarafem)
Olanzapine and fluoxetine (Symbyax)
Venlafaxine (Effexor XR)
Also in this Special Report
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