Seizures and Mood: Valproic Acid or Divalproex (Depakote)

Valproic acid or divalproex (Depakote) is an effective anticonvulsant for absence episodes and major motor seizures, and it is probably effective for partial motor seizures. It may be particularly effective when bilateral and multifocal spikes are present in the EEG. Its mechanism of action includes the propensity to increase levels of gamma-aminobutyric acid (GABA) and decrease dopamine turnover and N-methyl-d-aspartate-mediated depolarization (Hellings 1999; Keck et al. 1998). Valproate is also an excellent mood stabilizer and is superior to lithium for mixed, chronic, or atypical forms of bipolar disorder, even in children (Kowatch et al. 2000; Hellings 1999; Bowden et al. 1994; Swann et al. 1997). It has also been successfully used to treat aggression in patients with FXS and in patients with autism (Hagerman 1999a, 1999b; Davis et al. 2000; Kastner et al. 1993). Although Hellings (1999) reported that blood levels of 75-100 micrograms/dl produce greater behavioral improvement than levels of less than 75 in children with autism or pervasive development disorder (PDD), the dose should be started at 10 mg/kg/day and gradually increased to 20-30 mg/kg/day (McElroy and Weller 1997). The side effects of valproic acid include appetite changes, usually weight gain, thrombocytopenia, neutropenia, sedation, ataxia, fine tremor and hair thinning. Stomachaches can be avoided by taking valproic acid after meals. The most serious side effects are hepatic toxicity, pancreatitis, and cholecystitis (Buzan et al. 1995). Hepatic failure can occur, with the greatest risk (1 in 500) in young patients treated with multiple drugs (Dreifuss and Langer 1987).

Monitoring of valproate therapy includes complete blood count, platelet level, hepatic enzymes, electrolytes, and blood level of valproate. Occasionally, blood levels may need to be cautiously increased to 125 micrograms/dl to control behavior or seizures, but side effects must be carefully monitored (McElroy and Weller 1997). A report links the development of polycystic ovarian disease with long-term use of valproate in women (Isojarvi et al. 1993). This association requires further study and cautious use of valproate in girls with careful follow-up, particularly regarding the menstrual history.

Seizures and Mood: Lithium Carbonate

In the treatment of mood instability, a second mood stabilizer is often necessary (Kowatch et al. 2000). Often an atypical antipsychotic is utilized as described below. Lithium carbonate has a long history of use in treatment of bipolar disorder (Kafantaris 1995), aggression in children with conduct disorder (Campbell et al. 1995), or behavior problems in those with mental retardation (Dale 1980; Gadow and Poling 1988). Although anecdotal evidence suggests that it is also effective in patients with FXS (Hagerman 1996), there are no controlled studies using lithium for this syndrome. It is not the first drug of choice for stabilizing mood because of the need for careful monitoring of kidney function and blood levels and the risk of diabetes insipidus with long-term use. However, it is a useful medication that is often effective when other medications do not control aggression or 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.

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