Abstract
Butorphanol (Stadol) nasal spray (n.s.) is a mixed agonist-antagonist narcotic analgesic. It was heavily marketed in the early 1990’s as a migraine abortive. The charts of 1100 headache patients were reviewed, yielding 83 patients who had utilized butorphanol n.s. at least once. By chart review and patient interviews, the efficacy and tolerability of butorphanol n.s. was assessed. The diagnoses in the 83 patients were as follows: 71 had migraine plus chronic daily headache (cdh), 8 had migraine alone, 3 had cdh without migraine, and 1 suffered from cluster headache.
The butorphanol n.s. was effective (at least mildly) for 51% of patients. However, only 13 % were continuing to use the drug at the time of the study. 18 patients (22%) had overused or become addicted to the butorphanol n.s.. Most (13/18) of these overusers had a history of anxiety, while 14/18 reported previous depression. Of the 83 patients in the study, 63% suffered from anxiety, while 60% had a history of depression. While most patients in the study used 1 or 2 bottles of butorphanol n.s. per month, 10 patients utilized 15 or more bottles on a monthly basis.
At least one adverse event was reported by 49% of patients. They include: "Bad reaction, felt strange, weird, stoned, or numb", 25%, nausea or gastrointestinal upset, 11%, anxious, panic or ‘wired’, 8%, fatigue, 6%, dizzy or lightheaded, 5%, agitated or mean, 4%, pruritis or allergic, 4%, insomnia, 2%, tremulous, 2%, hallucinations, 1%, constipation, 1%, nasal irritation, 1%.
The results of this study indicate that, while butorphanol n.s. is effective for some headache patients, adverse events and addiction potential limit its use. Relatively few patients continue to utilize the drug over an extended period of time.
Descriptors
Butorphanol, Stadol, opioid, headache, migraine
INTRODUCTION
Opioid analgesics are occasionally necessary for selected headache patients. The non-addicting alternatives, particularly the triptans (sumatriptan, naratriptan, rizatriptan, etc.), work well for 60% to 70% of patients. (1) For those who do not respond, or cannot tolerate the usual migraine abortives, opioids may provide some relief. Butorphanol (Stadol) nasal spray (n.s.) is a mixed agonist-antagonistopioid analgesic. It was heavily marketed in the early 1990’s as a first-line migraine abortive. In a 1993 letter to the journal Headache, this author expressed several concerns about butorphanol n.s.. (2) I had observed a number of serious adverse events due to the use of butorphanol n.s.. In addition, the drug’s strong marketing campaign came into question.
The purpose of this study was to reassess results in my practice from the use of butorphanol n.s., in headache patients, from 1992 to 2001.
METHODOLOGY
Study Site
This was a retrospective study assessing the results of the utilization of butorphanol n.s., in headache patients. All of the subjects were headache patients treated at the Robbins Headache Clinic.
Patient Sample
The treating neurologist (the author) reviewed 1100 consecutive charts of headache patients, seen in the clinic from 1992 to 2001. Of the 1100, 83 patients (66 women, 17 men) were identified who had utilized butorphanol n.s. for headache, at least once. By chart review and patient interviews, the efficacy and tolerability of butorphanol n.s. was assessed.
RESULTS
DIAGNOSES
The diagnoses were made according to International Headache Society Classifications.(3) The diagnoses in the 83 patients were as follows: 71 had migraine plus chronic daily headache (cdh), 8 had migraine alone, 3 had cdh without migraine, and 1 suffered from cluster headache.
EFFICACY OF BUTORPHANOL N.S.
The Butorphanol n.s. was effective (at least mildly) for 51% of patients. However, at the time of the study only 13% of the patients were continuing to use the butorphanol n.s. for relief of their headache.
ANXIETY AND DEPRESSION
63% of the patients in this study suffered from anxiety, while 60% had a history of depression, unipolar or bipolar.
ADDICTION
18 patients (22%) had overused or become addicted to the butorphanol n.s.. Most (13/18) of these overusers had a history of anxiety, while 14/18 reported previous depression. While they were utilizing the butorphanol n.s., most patients used 1 to 2 bottles on a monthly basis. However, 10 patients utilized 15 or more bottles per month.
ADVERSE EVENTS
At least one adverse event was reported by 49% of patients. They include: "Bad reaction, felt strange, weird, stoned, or numb", 25%, nausea or gastrointestinal upset, 11%, anxious, panic or ‘wired’, 8%, fatigue, 6%, dizzy or lightheaded, 5%, agitated or mean, 4%, pruritis or allergic, 4%, insomnia, 2%, tremulous, 2%, hallucinations, 1%, constipation, 1%, nasal irritation,1%.
DISCUSSION
The results of this study indicate that, while butorphanol n.s is effective for some patients, adverse events and addiction potential limit its use. Relatively few patients continue to utilize the drug over an extended period of time.
Butorphanol is a mixed agonist/antagonist at the mu receptors, and acts as an agonist at the Kappa-opioid receptors.(4) The opioid agonist/antagonist drugs, such as butorphanol, pentazocine, and nalbuphine, were developed with the hope that the abuse potential and respiratory depression would be limited.(4) While these have generally been relatively safe medications, the abuse potential has appeared to be similar to the other opioids. The adverse event profile, particularly the cognitive effects, limit the usefulness of this class of opioid.
Initial studies, although small, on butorphanol n.s for headache were encouraging.(5) However, even in these studies the adverse events were significant. After the nasal spray form was approved for release in 1991, butorphanol was promoted as a safe and effective treatment for migraine. However, over the next several years a number of serious adverse events were reported, particularly related to addition. This resulted in the landmark study by Fisher and Glass, documenting the history of butorphanol n.s and the abuse potential. (4) As with other similar opioids, such as pentazocine, the initial claims by the manufacturer of butorphanol n.s. regarding limited abuse potential have not turned out to be true.
References
- Robbins L. Migraine abortive medication. In: 2nd Edition - Management of Headache and Headache Medications. New York: Springer-Verlag; 2000, 15-26.
- Robbins, L. Stadol Nasal Spray - Treatment for Migraine? Letter in Headache, April, 1993, Vol. 33, No. 4, pg. 220.
- Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988; 8 (Suppl. 7):1-96.
- Fisher, Morris, Glass, Stephanie. Butorphanol (Stadol): A study in problems of current drug information and control. Neurology 1997; 48: 1156-1160.
- Diamond S., Freitag FG, Diamond ML, Urban G. Transasal butorphanol in the treatment of migraine headache. Headache Quarterly. 1992;3:160-167.
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