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Assistant Professor of Medicinal Chemistry Department of Pharmaceutical and Biomedical Sciences Raabe College of Pharmacy Ohio Northern University 525 South Main Street Ada, Ohio 45810-1599 fax 419/772-1917 j-kuykendall{at}onu.edu
Clinical Associate Professor Department of Pharmacy Practice and Administrative Sciences College of Pharmacy Idaho State University Pocatello, Idaho
Published Online, September 28, 2004. www.theannals.com, DOI 10.1345/aph.1E231
Case Report. A 42-year-old man was prescribed metaxalone 800 mg twice daily (taken 400–1200 mg at bedtime several times weekly due to a shoulder injury). He began taking over-the-counter meclizine 25 mg (1–2 tablets) concurrently to treat nausea and gastrointestinal upset. Hallucinations occurred both just prior to sleep and at waking on over half of the occasions when maximum doses of each drug were taken together (10–12 times over 3 mo). Lower doses of each drug taken together did not elicit auditory hallucinations, and maximum doses of either drug alone were uneventful.
Auditory hallucinations were described as a purring sound of a cat or an unintelligible low-volume mumbling as if a radio were on in the next room (both of which often continued for minutes after waking) and occasions of intolerably loud music that interrupted sleep (but abruptly discontinued upon waking) or a loud, genderless voice calling his name as if to wake the patient. No visual hallucinations were reported. The patient realized that the sounds were not real and were probably drug-related. This prompted the discontinuation of the medications and restart several weeks later.
Auditory hallucinations disappeared upon discontinuation of the drug combination, but reappeared after the combination was reinstated. Ethanol was used prior to several of the events (estimated as <4 oz.), but was absent in others and did not seem to augment the intensity of hallucinations. Interestingly, a previous combination of two 10-mg cyclobenzaprine tablets with either meclizine 25–50 mg or diphenhydramine 25 mg at bedtime did not elicit auditory hallucinations.
The patient's past medical history included severe migraine headaches and mild osteoarthritis. No migraine medications were taken during this time period, but ibuprofen 800 mg up to twice daily and glucosamine/chondroitin sulfate were taken regularly. Use of illicit drugs, herbal preparations, or dietary supplements was denied. A family history of depression was noted, but no major psychiatric disorders. Previous military and job-related psychological evaluations (within the past 10 y) revealed no abnormal thought or behavior patterns.
Discussion. Hallucinations induced by anticholinergic antihistamines are well known, but usually of a visual nature.1-4 The presumed interaction of metaxalone and meclizine to cause hallucinations of any type has not been reported previously. Auditory hallucinations are not common adverse drug reactions, although use of the Naranjo probability scale indicated that an interaction was probable.5 It must be noted that it is difficult to discern whether the reported events constitute a true drug–drug interaction or an idiosyncratic reaction for this single patient. It may be prudent to use caution when histamine1-antagonists are used with centrally acting muscle relaxants, particularly in patients prone to hallucinations or psychotic behavior. This may be particularly important in children and elderly patients, who are generally more susceptible to the actions of anticholinergics.
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