Why aren't lower, effective, OTC doses available earlier by prescription?

Many popular oral over-the-counter (OTC) drugs were originally available only by prescription, but not at the low doses contained in their OTC counterparts. Yet, if OTC doses are effective for treating mild symptoms, why weren't these low, often safer doses made available at least by prescription when the drugs were first approved?

To examine issues surrounding the delayed approval of OTC doses by the Food and Drug Administration (FDA).

Information reviewed included package inserts, data obtained from manufacturers, and articles published in MEDLINE (1966 to December 2001). Medications examined included presently available and potentially approved OTC antiinflammatory, gastrointestinal, and antihistamine drugs.

Considerable data demonstrate the effectiveness of ibuprofen, naproxen, ranitidine, famotidine, nizatidine, diphenhydramine, and clemastine at OTC doses. Published studies also show the effectiveness of celecoxib, omeprazole, and fexofenadine at doses 33-50% lower than currently recommended for prescription use.

OTC doses are effective for many patients with mild symptoms and for some with serious symptoms. However, OTC-like doses are usually not offered when drugs are approved for prescription use because new drugs are usually studied in patients with serious conditions requiring higher doses; manufacturers and the FDA seem to prefer a middle-dose approach; >75% of subjects in premarketing dose studies are male; and averaging the responses of study subjects may obscure a wide range of interindividual variation in drug response. Simplistic dosage guidelines make therapeutic decisions easier. Because dose-related adverse effects frequently diminish quality-of-life and reduce adherence, the early availability of OTC-like doses, at least by prescription, would allow healthcare professionals greater flexibility in matching medication doses to patients' widely differing needs.