Valproate neuroleptic drugs

The combination of valproate and traditional neuroleptic drugs, a first-line treatment for mixed or rapid-cycling episodes or dysphoric mania with psychotic features, is associated with altered mental status and electroencepha-lographic abnormalities (641). 

Oxcarbazepine is a weaker enzyme inducer than carbamazepine. When it is substituted for carbamazepine, plasma concentrations of concomitant drugs, such as valproate and neuroleptic drugs, can rise, owing to deinduction, leading to potential toxicity (17,18). 

Halman et al. (491) conducted a retrospective chart review on 11 patients who were HIV-positive and presented with an acute manic episode. Whereas the six patients with abnormal MRI findings demonstrated intolerance to standard drug treatment (i.e., lithium, conventional neuroleptics), all benefited from a trial with an anticonvulsant (e.g., valproate, CBZ, clonazepam). 

There is little evidence that lithium is superior to other drugs with sedative actions for the treatment of acute mania. Benzodiazepines, neuroleptics and anticonvulsants have all been tried in mania and none have been found to be inferior to lithium. Two small studies of clonazepam in mania found it was superior to lithium (Chouinard 1988 Chouinard, Young, Annable 1983). All new- and old-generation neuroleptics have been found to be more effective than placebo (Perlis et al. 2006). Comparisons of lithium with the sedative anticonvulsants carbamazepine and sodium valproate show similar effects (Bowden et al. 1994 Freeman et al. 1992 Lerer et al. 1987 Small et al. 1991). 

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