Anticonvulsant agents valproate

Support is scant for the efficacy of anticonvulsant agents in the treatment of OCD (Jenike 1990 Joffe and Swinson 1987). If there is a role for carbamazepine in OCD, it may be in patients with clinical or electroen-cephalographic evidence of a seizure disorder (Jenike and Brotman 1984 Khanna 1988). The anti-OC efficacy of combined SRI-carbamazepine treatment has not been adequately studied. Sodium valproate was found ineffective in two cases of OCD (McElroy and Pope 1988 McElroy et al. 1987). However, one author has suggested that sodium valproate may be a useful pretreatment for patients with OCD who might otherwise tolerate SRIs poorly (Deltito 1994). The anticonvulsant clonazepam is discussed earlier in this chapter. 

Children under valproate therapy have an increased incidence of fatal hepatotoxicity, particularly if the drug is used in combination with other anticonvulsant agents. When used as monotherapy, the risk declines substantially. Children under two years old have the greatest risk of hepatotoxicity (approximately 20-fold), so if the drug is to be administered, it should be used as monotherapy and carefully monitored. 

Well known for their clinical role as antimanic agents, anticonvulsants such as carbamazepine and valproate have also been used in both bipolar and unipolar TRD (Post et al. 1994a, 1994b). In one series. Post et al. (1994a) found a greater response in patients with bipolar (15/40) versus those with unipolar (2/17) TRD. Open studies of valproate also suggest limited antidepressant efficacy, but only a paucity of data with anticonvulsants on TRD exists. More recently, in open trials, lamotrigine (a partial anticonvulsant that inhibits glu-... 

Like adults, some adolescents do not respond to lithium, and clinicians often try an anticonvulsant, such as valproate or carbamazepine. The use of these agents is based primarily on their antimanic activity in adults because only a limited number of case reports about the treatment of bipolar adolescents with CBZ are available (207). There are 29 reports in the world literature, however, examining the efficacy of CBZ in the treatment of behavioral dyscontrol or high activity level in children. Of... 

Anticonvulsants such as valproate and CBZ are effective mood-stabilizing agents and may be useful in withdrawal states from alcohol, BZDs, and cocaine... 

For patients with bipolar affective disorder (manic-depressive illness) lithium, usually in the form of lithium carbonate, has been the main prophylactic agent for the last forty years. However, during the last ten years certain anticonvulsants (carbamazepine and sodium valproate) have also been found to be effective. 

Although a number of mood-stabilizing drugs are commonly used in the treatment of BAD, lithium and the anticonvulsants valproate (VPA) and carba-mazepine are the only drugs for which long-term efficacy has been established, and are therefore used for maintenance treatment of BAD (Belmaker, 2004). However, these agents are far from the perfect medications, and they are ineffective and not well tolerated by a significant portion of patients. 

Two anticonvulsants, carbamazepine (Tegretol) and valproic acid, also referred to as valproate (Depakote, Depakene), have proven mood-stabilizing properties (see figure 15-E). These agents are most useful when lithium is contraindicated or when a patient does not respond to or cannot tolerate lithium. Rapid cyclers, who often are poorly controlled with lithium, are good candidates for one of these alternative agents. Valproic acid appears to be indicated more for manic or mixed states of bipolar disorder, and is probably not as effective in depressed states. The anticonvulsants are often employed in conjunction with lithium. 

A third group of toxins are those which give rise to acute hepatocellular failure only in certain individuals who are susceptible. Important examples include sodium valproate, an anticonvulsant drug which gives rise to toxicity in some children, and halothane, an anaesthetic agent. 

Sedatives or anticonvulsants (e.g., carbamazepine, oxcarbazepine, phenobarbital, and pheny-toin, but not valproate) that induce CYPs (see Chapter S) can enhance the metabolism of antipsychotic and many other agents (including anticoagulants and oral contraceptives), sometimes with significant clinical consequences. Conversely, selective serotonin (5-HT) reuptake inhibitors including fluvoxamine, fluoxetine, paroxetine, venlafaxine, sertraline, and nefazodone (see Chapter 17) compete for these enzymes and can elevate circulating levels of neuroleptics. 

As for mixed states, evidence for superiority of one treatment over another is as yet limited. Anticonvulsants such as valproate and carbamazepine seem to be as efficacious as lithium, while other possibilities include the combination of either valproate or lithium with an antipsychotic agent. 

Epilepsy is a disorder characterized by recurrent spontaneous electrical discharges within the brain which are manifested by clinical seizures. Four million patients in the United States are afflicted with this ailment 20% of these have seizures that cannot be controlled sufficiently with existing medications to permit normal activities of everyday life. The market for anticonvulsants is substantial a historical growth rate of 10 to 12% is expected to be sustained thereafter. Epileptic seizures can be classified as primary epilepsies (35%) or partial epilepsies (65%). Primary epilepsies (generalized convulsions) can be controlled with valproate (Depakote), carbamazepine (Tegretol), phenytoin (Dilantin), or phenobarbi-tol. Most partial epilepsies have resisted control with chemotherapeutic agents. 

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