Letter to the editor

Perspectives in Psychiatric Care, Jul-Sep 2003 by Shields, Brenda J, Nahata, Milap C

Efficacy of brand-name vs. generic fluoxetine

Although most generic drugs can be substituted for brands cost-effectively, the following case suggests that this may not be possible for some patients on fluoxetine. A 38-year-old woman presented to her family physician in May 1996 complaining of "feeling sad all the time for no logical reason," difficulty sleeping through the night, loss of interest in all things that were previously pleasurable, withdrawal from social interactions, and suicidal ideation. After being diagnosed with major depression, she was prescribed 10 mg of fluoxetine (Prozac) daily. The symptoms began to diminish, but were still present. The dosage was increased to 20 mg daily in November 1996, which relieved her symptoms until April 1997, when she began feeling depressed monthly for approximately 1 week prior to menstruation. After consultation with a psychiatrist the dose of Prozac was increased to 30 mg daily. The symptoms disappeared until November 1997, when she reported feeling depressed prior to menstruation. The dose was then increased to 40 mg daily. She remained symptom free until October 2001, when the generic form of fluoxetine became available on the U.S. market. The patient's insurance company would no longer pay for Prozac and the patient was switched to an equivalent dose of a generic fluoxetine, 40 mg daily. There was no washout period between taking the brand name and the generic.

Sixteen days after the treatment with generic fluoxetine, the patient reported that she was "feeling sad all the time for no logical reason" and having difficulty sleeping through the night. Since her insurance would no longer cover Prozac, her physician recommended switching to Prozac Weekly, which was not available in generic form and, therefore, would be covered by the insurance company. The patient stopped taking generic fluoxetine on November 9, 2001, and began taking Prozac Weekly, 90 mg, twice weekly on Mondays and Thursdays, on November 12, 2001. On a follow-up visit to her physician 2 weeks later, the patient was symptom free.

In November 2002, the patient again reported suicidal ideation and sleep disturbances. She was prescribed 10 mg of Elavil at bedtime to help with the sleep disturbances. Two weeks later, the patient reported she was able to sleep through the night, but was still having suicidal ideations. It was realized that the twice weekly dose of Prozac Weekly averaged 25.7 mg/day, which was considerably less than the 40 mg/day dose of Prozac at which the patient had previously remained symptom free for several years. The dosage was then increased to 90 mg of Prozac Weekly every other day. This dosage regimen resulted in 3 or 4 doses per week, averaging 38.6-51.4 mg/day. The patient was symptom free on January 2, 2003, and continues to remain so.

The patient had no history of drug, alcohol, or substance abuse. She took one Claritin-D 12 hr tablet daily during the entire course of Prozac therapy and was on Triphasil-28 from October 1998 through June 1999.

According to the Naranjo probability scale (Naranjo et al., 1981), this adverse effect of generic fluoxetine can be classified as probable. The apparent therapeutic inequivalence of generic fluoxetine has been observed twice before (Albrecht & Adler, 2001; Hovaguimian, 1998). Although serum fluoxetine concentrations were not determined, the possibility that the generic fluoxetine may not be therapeutically equivalent to Prozac must be considered. Comparative pharmacokinetic and efficacy studies of brand and generic fluoxetine are needed to establish their therapeutic equivalence.

References

Albrecht, J., & Adler, R. H. (2001). Therapeutic inadequacy in spite of bioequivalency on replacing Fluctine(R) with Fluocim.(R) Swiss Medical Weekly, 131, 84.

Hovaguimian, T. (1998). Generique et obsessions ou obsession du generique. A propos d'un cas de rechute d'un trouble obsessionnel compulsif lors d'une substitution de la fluoxetine par un generique [Generics and obsessions, or obsession with generics: A case of obsessive-compulsive disorder following a substitution of fluoxetine with a generic]. Medecine et Hygiene, 2229, 2085-2087.

Naranjo, C.A., Busto, U., Sellers, E.M., Sandor, P., Ruiz, L, Roberts, E.A., et al. (1981). A method for estimating the probability of adverse drug reactions. Clinical Pharmacology and Therapeutics, 30, 239-245.

The authors thank Dr. Anne Joliot for translating the Hovaguimian article into English. The authors have no financial relationship of any type with the manufacturer of Prozac.

Brenda J. Shields, MS

Shieldsb@pediatrics.ohio-state.edu

Research Coordinator, Center for Injury Research and Policy

Children's Hospital, The Ohio State University College of Medicine and Public Health

Milap C. Nahata, PharmD

Professor of Pharmacy, Pediatrics and Internal Medicine

The Ohio State University

Columbus, OH