Dependence epilepsy treatment

S. Stockier, B. Plecko, S.M. Gospe Jr., M. Coulter-Mackie, M. Connolly, C. Van Karnebeck, S. Mercimek-Mahmutoglu, H. Hartman, G. Scharer, E. Struijs, I. Tein, C. Jacobs, P. Clayton, and J.L. Van Hove. Pyridoxine-dependent epilepsy and antiquitin deficiency Clinical and molecular characteristics and recommendations for diagnosis, treatment and follow up. Mol. Genet. Metab. 104 48-60 (2011). 

The treatment of choice depends on the type of epilepsy (Table 52-2) and on drug-specific adverse effects and patient preferences. Fig. 52-1 is a suggested algorithm for treatment of epilepsy. 

Phenobarbital, mephobarbital and metarbital are the only oral anticonvulsants which are effective at sub-hypnotic levels. Many barbiturates are classified as Schedule II, III, or IV due to their high potential for overdose and dependence. Abrupt withdrawal may cause seizures, restlessness, trembling, and insomnia and may be fatal. Phenobarbital is used as an anticonvulsant for the treatment of epilepsy and in some combination medications for the relief of irritable bowel syndrome. 

Membrane-bound enzymes, particularly the ATPases involved in the ionic pumps for calcium, sodium and potassium, have been found to function abnormally in the brains of epileptic patients and animals. A reduction in Na+K+-ATPase activity has been reported in human focal epileptogenic tissue, but it is uncertain whether such changes are due to the disease itself or a reflection of drug treatment. Similar changes have, however, been reported in experimental animals following the localized application of alumina cream and in DBA/2 mice that exhibit sound-induced seizures a reduction in calcium-dependent ATPase has also been found in the brain of DBA/2 mice. Such findings are consistent with the hypothesis that a defect in ion channels may occur in epilepsy. 

Of the more recently introduced methods for smoking cessation, bupropion (an antidepressant with dopaminomimetic properties) has recently been introduced. Clinical trial data, in which the nicotine patch, bupropion at 300 mg, and a combination of the two drugs were compared with placebo treatment, have shown cessation of smoking rates of 36% for the patch, 49% for bupropion and 58% for the combined treatments following 7 weeks of treatment. The placebo response rate was 23%. All subjects received relapse prevention therapy. Thus bupropion appears to be a reasonably safe and effective treatment for nicotine dependence. It is however contraindicated in those subject to epilepsy its main side effects are dry mouth and insomnia. 

Flupirtine was the first compound identified to affect KCNQ channels and has been used in man to treat pain. However, only recently has this drug been shown to be an activator of Kv7 channels (see Munro and Dalby-Brown 2007). The clinical efficacy of flupirtine was originally postulated to occur through receptor-dependent mechanisms, but as noted by Munro and Dalby-Brown (2007) it is likely that Kv7 channel activation occurs at clinically relevant exposure levels. Retigabine, a flupirtine analog, is currently in clinical trials for the treatment of epilepsy and pain and has been the most widely used tool to explore both the in vitro and in vivo effects of Kv7 activation. This compound was initially shown to increase K+ channel activity in a neuroblastoma cell line (Rundfeldt 1997 see also Rundfeldt 1999) and subsequently was... 

Carbamazepine is used in the treatment of epilepsy and trigeminal neuralgia. Unlabeled uses include treatment of postherpetic pain syndrome, neurogenic diabetes insipidus, bipolar disorder, alcohol withdrawal, and cocaine dependence. 

Epilepsy is a clinical diagnosis defined by recurrent seizures. Controversy surrounds the most appropriate time to initiate AED therapy. Many clinicians do not initiate treatment until a second unprovoked seizure has occurred. Some clinicians start AED treatment after the first seizure, whereas others may initiate prophylactic treatment following a CNS insult thought likely to cause epilepsy eventually (e.g. stroke or head trauma). Appropriate treatment decisions may vary depending on individual patient clinical characteristics and circumstances. 

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