Anticonvulsants mental retardation

Lamotrigine is an anticonvulsant drug that attenuates some forms of cortical glutamate release via inhibition of sodium, calcium, and potassium channels. An open-label case series (Uvebrant and Bauziene, 1994) and a case report (Davanzo and King, 1996) described improvement in autistic symptoms and self-injurious behavior, irritability, disturbed sleep, and social impairment in autistic children and an 18-year-old female with profound mental retardation, respectively, who were treated for epilepsy. 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

Serious hepatotoxicity is possibie but rare. Hepatic failure occurs in only one in 40,000 cases and appears to be an idiosyncratic reaction that is not dose-related. Children under the age of 2, especially those receiving anticonvulsant polypharmacy, with mental retardation, and/or with poor nutritional status have been shown to be at greatest risk (351, 352). To our knowledge, no cases of hepatic failure have been reported in adults with bipolar disorder who were receiving VPA monotherapy, but liver failure has been reported in older children and in a mentally retarded adult with epilepsy taking VPA alone ( 77, 352, 353). 

In a study of serum concentrations of the anticonvulsants phenytoin, phenobarbital, and carbamazepine, before and after mentally retarded patients received flu vaccine, the... 

H3. Houben, P. F., Hommes, O. R., and Knaven, P. J., Anticonvulsant drug and folic acid in young mentally retarded epileptic patients. A study of serum folate, fit firequency and I.Q, Epilepsia 12, 235-247 (1971). 

N.L. 5 F Fits. Mental retardation. No anticonvulsants. 2485 U/liter" Bone 7... 

L14. Lifshitz, F., and Maclaren, N. F., Vitamin D-dependent rickets in institutionalized, mentally retarded children receiving long-term anticonvulsant therapy. I. A survey of 285 patients. J. Pediatr. 83, 612-620 (1973). 

Tolman, K. G., Jubiz, W., Sannella, J. J., Madsen, J. A., Belsey, R. E., Goldsmith, R. S., and Preston, J. W., Osteomalacia associated with anticonvulsant drug therapy in mentally retarded children. Pediatrics 56, 45-51 (1975). 

Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid and its derivatives. Children less than 2 years of age are at considerable increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. 

Maclaren N, Lifshitz F. Vitamin D-dependency rickets in institutionalized, mentally retarded children on long term anticonvulsant therapy. II. The response to 25-hydro> cholecalciferol and to vitamin D2. PecSatrRes( 973) 7, 914-22. 

---