Anticonvulsants adverse effects

Vigabatrin has an unacceptable adverse effect profile, but consistent findings in animal studies suggest that GABA agonists deserve further study. a-AMPA antagonism, or antikindling action, may also be important for some anticonvulsants. 

Electroconvulsive therapy (ECT) is used for severe mania or depression during pregnancy and for mixed episodes prior to treatment, anticonvulsants, lithium, and benzodiazepines should be tapered off to maximize therapy and minimize adverse effects. 

I with seizures and require anticonvulsant therapy. Phenytoin is the most frequently used agent, with a loading dose of 15 mg/kg followed by 300 mg by mouth daily (titrated to therapeutic levels between 10 and 20 mcg/mL). Diazepam 5 mg intravenously may be used for rapid control of persistent seizures. Prophylactic anticonvulsants have been used frequently, but a recent meta-analysis did not support their use.23 Thus, because adverse effects and drug interactions are common, the routine use of prophylactic anticonvulsants is not recommended. 

De Ponti, F. et al., Immunological adverse effects of anticonvulsants What is their clinical significance, Drug Safety, 8, 235, 1993. 

In partially responsive or nonresponsive patients, the first issue is to determine whether an individual is truly treatment-resistant, because many receive nontherapeutic doses and the potential for improvement may not be adequately tested. Thus, in some situations, more aggressive treatment (dose increase, augmentation) may be appropriate, if not precluded by adverse effects. In selected cases, it may also be helpful to monitor plasma levels to ensure that they are in a reasonable range (see Pharmacokinetics/Plasma Levels earlier in this chapter). If a patient continues to demonstrate significant symptoms after a sufficient trial (2 to 3 weeks), alternatives to switching to another antipsychotic may include the addition of lithium, an anticonvulsant, or a second antipsychotic agent. An antidepressant or anxiolytic may also be helpful, especially if affective or anxiety symptoms are prominent. 

Typical doses of clonazepam have been in the range of 2 to 16 mg/day given on a once or twice per day schedule due to its longer half-life. A major advantage of this anticonvulsant is its relative lack of adverse effects and freedom from laboratory monitoring in comparison with CBZ and VPA. Clonazepam may be more useful when combined with lithium or CBZ rather than as a specific antimanic agent, perhaps supplanting the need for antipsychotics. In this sense, it can be viewed as a behavioral suppressor, rather than a true mood stabilizer (121). 

ADVERSE EFFECTS OF LITHIUM, VALPROATE, AND OTHER ANTICONVULSANTS... 

Changes in body weight associated with anticonvulsants have been reviewed (116), including the effects of the antiepileptic drugs that have been most commonly associated with this adverse effect (valproic acid, carbamazepine, vigabatrin, and gabapentin) (117). Unlike most anticonvulsants, topiramate, felbamate, and zonisamide can cause weight loss. 

Hyperammonemia and carnitine deficiency are adverse effects of valproate, although carnitine deficiency can also be caused by other anticonvulsants (132). 

Carbamazepine has been considered to be a reasonable alternative to lithium when the latter is less than optimally efficacious. It may be used to treat acute mania and also for prophylactic therapy. Adverse effects (discussed in Chapter 24 Antiseizure Drugs) are generally no greater and sometimes are less than those associated with lithium. Carbamazepine may be used alone or, in refractory patients, in combination with lithium or, rarely, valproate. The mode of action of carbamazepine is unclear, but it may reduce the sensitization of the brain to repeated episodes of mood swing. Such a mechanism might be similar to its anticonvulsant effect. 

Relling MV, Pui C-H, Sandlund JT, et al. Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukemia. Lancet 2000 356 285-290. 

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