Letters to the Editor

Tolerance and Dependence Risk with the Use of Carisoprodol

to the editor: Carisoprodol (Soma) is an unscheduled muscle relaxant commonly used in primary care. It is metabolized to meprobamate, a schedule IV drug that has a long history of abuse and exhibits cross-tolerance to barbituates. A small but growing amount of literature is available regarding morbidity associated with the use of carisoprodol, including respiratory compromise1 and vehicle crashes.2 This case report highlights this potential danger.

A 45-year-old man with grand mal seizure disorder, opiate dependence, major depressive disorder, and chronic neck and back pain presented with new-onset nocturnal "blackouts." He had no history of barbiturate abuse. He described at least three episodes during the past two weeks in which he was found wandering in his neighborhood naked. He had no memory of these events, and could only relate them based on the reports of his neighbors. Although admitting to ongoing intravenous heroin use, there was no apparent temporal link between heroin and these events. He denied recent use of alcohol or other drugs, symptoms of aura or a postictal state, recent head injury or illness, or overuse of his prescribed medications.

His medications at admission and for at least the previous month were: carisoprodol, 700 mg three times daily; gabapentin (Neurontin), 600 mg three times daily; quetiapine (Seroquel), 25 mg every night; zolpidem (Ambien), 10 mg every night; sertraline (Zoloft), 200 mg every night; and ibuprofen, 800 mg three times daily.

Physical examination showed his vital signs were within normal limits. He was alert, oriented, and scored 30 out of 30 on the Mini-Mental State Examination. Urine was only positive for opiates (routine urine drug screens do not detect meprobamate). Electrolytes, liver function tests, complete blood count, vitamin B12, folate, and thyroid-stimulating hormone levels were within normal limits. An electroencephalogram and a noncontrast head computed tomographic scan were unremarkable.

We suspected that he was experiencing amnestic periods secondary to his use of multiple psychoactive medications. Rather than discontinue carisoprodol abruptly, particularly given his seizure disorder, a pentobarbital challenge test was performed to assess his tolerance level to carisoprodol. The pentobarbital challenge test3 involves administration of a test 200 mg dose of pentobarbital and assessment of the patient one hour later for one of four stages of barbiturate tolerance. The patient showed no symptoms of intoxication, indicating that he was at the highest stage of tolerance and, therefore, at risk of delirium, seizures, or even death with abrupt carisoprodol cessation.4 He was placed on a one-week phenobarbital taper and was both seizure-free and without amnestic episodes during his two-week stay. He left the hospital receiving baclofen (Lioresal), 5 mg three times daily, for his back spasms; carisoprodol, gabapentin, zolpidem, and quetiapine were successfully discontinued.

This case report demonstrates clear barbiturate tolerance caused by the use of carisoprodol. The tolerance and dependence liability of carisoprodol can put patients at risk of severe withdrawal symptoms, including seizures and death. It is a curious inconsis-tency that carisoprodol is not scheduled, but meprobamate is schedule IV.

CRAIG HEACOCK, M.D.
MARK S. BAUER, M.D.
Department of Psychiatry
Veterans Affairs Medical Center, 116R
830 Chalkstone Ave.
Providence, RI 02908-4799

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Veterans Affairs.

REFERENCES

1. Davis GG, Alexander CB. A review of carisoprodol deaths in Jefferson County, Alabama. South Med J 1998;91:726-30.

2. Logan BK, Case GA, Gordon AM. Carisoprodol, meprobamate, and driving impairment. J Forensic Sci 2000;45:619-23.

3. Bauer MS. Field guide to psychiatric assessment and treatment. Philadelphia, Pa.: Lippincott Williams & Wilkins, 2003.

4. Littrell RA, Hayes LR, Stillner V. Carisoprodol (Soma): a new and cautious perspective on an old agent. South Med J 1993;86:753-6.

Atypical Laryngeal Dystonia Caused by an Antiemetic

to the editor: Antiemetics that block dopamine receptors (such as metoclopramide or prochlorperazine) are known to potentially cause all of the side effects associated with antipsychotic medications: akathisia, extrapyramidal side effects, and acute dystonic reactions.1 Acute dystonic reactions are often dramatic and are potentially life threatening if the closing of the larynx causes asphyxia. Reports of milder or atypical variants of this reaction are rare.2 This case report describes a patient who has throat discomfort and aphonia as atypical observations of laryngeal dystonia. These subtle manifestations often may be overlooked.

A 36-year-old woman with no history of psychiatric problems and no previous exposure to antipsychotic drugs was prescribed prochlorperazine, 10 mg four times daily, for residual nausea following aborted treatment with erythromycin for upper respiratory symptoms. She had taken three doses of prochlorperazine over 24 hours when she had to stop lecturing her college class because her voice gave out and became a mere whisper. That evening she made herself some hot tea for her "throat discomfort" and "tired voice." Incidentally overhearing this woman describe her day and symptoms to her husband, I was concerned that she might be experiencing an acute dystonic reaction. I advised her to take two 25-mg diphenhydramine tablets from her medicine cabinet immediately and repeat the dose one hour later. She described no other symptoms such as muscle stiffness, neck stiffness, difficulty breathing, or problems with her eyes. Several hours later, the throat discomfort had completely resolved, and she had no further difficulties with her voice. She continued taking 50 mg of diphenhydramine twice daily for another three days.

The time-course and treatment-response of this patient's symptoms are highly suggestive of acute dystonia. As opposed to the treatment given in her case, the optimal treatment of an acute dystonic reaction involves administering parenteral benztropine or parenteral diphenhydramine.3 Once successfully begun, the anticholinergic or antihistaminergic treatment should be continued orally for another two or three days to prevent recurrence.

I proffer the term "Hot Cup-Of-Tea Sign" for subtle laryngeal dystonia experienced merely as throat discomfort. Use of this term might help to increase the recognition of manifestations other than oculogyric crisis and opisthotonus for acute dystonic reactions. The small but definite risk of the serious reaction of laryngeal dystonia with antidopaminergic antiemetics should be considered before using these agents. Most nonpsychiatric patients are by default neuroleptic-naïve and, thus, potentially sensitive to dopamine blockers.

OLIVER FREUDENREICH, M.D.
MGH Schizophrenia Program
Freedom Trail Clinic
25 Staniford St., 2d Fl.
Boston, MA 02114

REFERENCES

1. Miller LG, Jankovic J. Drug-induced dyskinesias: an overview. In: Joseph AB, Young RR, eds. Movement disorders in neurology and neuropsychiatry. 2d ed. Malden, Mass.: Blackwell Science, 1999:5-30.

2. Koek RJ, Pi EH. Acute laryngeal dystonic reactions to neuroleptics. Psychosomatics 1989;30:359-64.

3. Arana GW, Hyman SE, Rosenbaum JF. Handbook of psychiatric drug therapy. 4th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins, 2000.

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