Seizures and Mood: Carbamazepine (Tegretol)

The majority of males with FXS and seizures have a benign variety with rolandic spikes, and these patients usually respond well to anticonvulsants (Wisniewski et al. 1991; Musumeci et al. 1999). Carbamazepine (Tegretol) is the most commonly used anticonvulsant in FXS, perhaps because it has a beneficial behavioral effect in addition to the anticonvulsant effect. Carbamazepine is an iminostilbine with a tricyclic structure unique among anticonvulsants. It is the drug of choice for partial motor, partial complex, and secondary generalized tonic-clonic seizures. It is usually well tolerated, but up to 30% of individuals may experience sedation, which is usually transient. The dosage is gradually increased from a starting dosage of 10 mg/kg/day to a maintenance dosage of 20-40 mg/kg/day. Carbamazepine is usually given two or three times a day, and side effects may rarely include a rash, hyponatremia, hematopoietic alterations, and liver toxicity. A benign transient neutropenia occurs in up to 20%, but it rarely requires discontinuation of the medication (Dodson 1989). Serious severe hematologic problems such as agranulocytosis are very rare (Pellock 1987). An occasional patient will develop behavioral problems such as hyperactivity. Concurrent treatment with macrolide antibiotics (including erythromycin), cimetidine, propoxyphene, isoniazid, fluoxetine, and paroxetine can interfere with the metabolism of carbamazepine, causing an increase in the serum levels and possible development of symptoms of toxicity, including nausea, vomiting, ataxia, lethargy, and diplopia (Pippenger 1987).

In approximately 3% of patients treated with carbamazepine, a hypersensitivity reaction may be seen within 2 to 4 weeks of initiation of the medication. This presents with fever and a cutaneous eruption, sometimes like erythema multiforme (Bellman et al. 1995). Patients who are started on carbamazepine should be told to discontinue the medication if a rash develops. Some patients may require treatment with steroids if the hypersensitivity syndrome does not disappear after carbamazepine is discontinued.

Carbamazepine is helpful for behavioral and psychiatric disorders in both retarded and nonretarded patients (Berkheimer et al. 1985; Evans and Gualtieri 1985). Problems including episodic dyscontrol, violent outbursts, hyperactivity, and self-injurious behavior may respond to carbamazepine in those with or without EEG abnormalities or seizures (Reid et al. 1981; Langee 1989). Although some patients may respond to the anticonvulsant effect (i.e., the EEG abnormalities that may have precipitated the outburst are improved), there is also a direct effect on behavior, which includes stabilization of the mood (Ryan et al. 1999; Kowatch et al. 2000).

No controlled studies of the effect of carbamazepine on behavior problems in FXS have been carried out. Gualtieri (1992) reported anecdotally that carbamazepine was helpful for behavior problems resulting from mood instability in 8 or 9 patients with FXS. Carbamazepine may also be used with a variety of other medications, including stimulants and antidepressants described below. A study by Langee (1989) showed improvement in 39% of 76 mentally retarded institutionalized males with behavior problems (usually aggression or episodic dyscontrol) when treated with carbamazepine. This is a medication, therefore, that should be considered in violent or significantly aggressive males with FXS, particularly those with EEG findings of spike wave discharges or those with significant mood instability.

This article is not intended to give medical advice for individual cases.  Any change in medical treatment should be done in consultation with appropriate medical personnel. This article is written for medical professionals.  Some of the terms will be unfamiliar to those who are not trained in medical fields. *This article is from the chapter on treatment in the 3rd edition of Fragile X Syndrome: Diagnosis, Treatment, and Research edited by Randi Jenssen Hagerman, M.D. and Paul Hagerman, M.D., Ph.D., to be published May 2002.  It is included with permission from The Johns Hopkins University Press. References to other chapters refer to chapters in the book which are not included as part of this website. The complete 3rd edition of Fragile X Syndrome: Diagnosis, Treatment, and Research can be ordered from the National Fragile X Foundation by calling 1-800-688-8765 or from The Johns Hopkins University Press at 1-800-537-5487.

Medical Follow-up   Pharmacotherapy   Future Prospects
Outline   Medications   Medical Conditions
References: A, B, C, D, EF, G, H, IJ, K, L, M, NOP, QR, S, T, UVWXYZ
 

© copyright 1998-2008 NFXF