Post-marketing experience with an opioid nasal spray for migraine: lessons for the future

In 1992 a nasal spray formulation of butorphanol, an opioid medication intended for pain relief, was marketed in the USA on an unscheduled basis. Only a few years later, amid widespread reports of abuse and dependence, primarily in migraine patients, its manufacturer voluntarily requested the Food and Drug Administration to reschedule the drug as a Schedule IV narcotic. The events surrounding this episode are reviewed, and four problem areas that might have contributed are identified: (i) inadequate review of previous experience with other formulations of butorphanol; (ii) failure to consider the impact of disease state and drug formulation on the risk of adverse events; (iii) the limited scope of clinical trials prior to approval; and (iv) aggressive marketing efforts. The implications of these lessons for future drug development and post-marketing surveillance in the migraine field are considered.