Valproate In Patients Research Articles

Valproate monotherapy in partial seizures

Results of a retrospective study in 30 patients indicate that, contrary to the findings of some earlier studies, valproate monotherapy is highly effective in the treatment of partial seizures, especially those that become secondarily generalized. In 22 of these 30 patients (73 percent), valproate monotherapy either abolished seizures (12 patients) or reduced their frequency by at least 51 percent (10 patients), whereas eight patients experienced minimal or no reduction in seizure frequency. All these patients had previously experienced treatment failure with carbamazepine, phenytoin, or phenobarbital—either alone or combined—because of lack of efficacy or unacceptable side effects. In these patients, failure to have a response to valproate therapy appeared to be related to the type of seizure (simple partial seizures alone/complex partial seizures alone, without secondarily generalized tonic-clonic seizures) and longer duration of uncontrolled seizures. Although these results cannot be generalized to all patients with partial seizures, they do indicate that a double-blind randomized trial of valproate in patients with all types of partial seizures is warranted.

Electroencephalographic and behavioural effects of sodium valproate in patients with photosensitive epilepsy. A single dose trial.

A single oral dose of Sodium valproate (VPA) given as Epilim (10 mg/kg) inhibited photoconvulsive responses, especially to 15--30 Hz frequency flicker, in seven out of ten patients with photosensitive epilepsy. In addition, in all patients (with an exception of one) the amplitude of the secondary slow negative wave of the visual evoked potentials was reduced 4--5 h after drug administration. However, in five of these patients the normalization of electrocortical reactions to a single flash and flickering light was accompanied by somnolence and fatigue, moderate slowing of EEG background, development of 3 Hz spike-wave activity and (in three patients) augmented response to hyperventilation. In two patients the EEG photoconvulsive discharge was exaggerated by VPA. There VPA effects suggest that photosensitivity and the underlying epileptic condition have overlapping albeit different pathophysiology. The data offer no support for the conclusion that reduced photosensitivity produced by VPA is associated with the therapeutic potency of the drug.

Valproate in Nonketotic Hyperglycinemia

Severe intractable seizures are frequent manifestations of nonketotic hyperglycinemia. Because levels of urinary and plasma glycine have been reported to be elevated by valproate in patients with seizures but no evidence of hereditary hyperglycinemia,1,2 it has been assumed that the agent is contraindicated for the therapy of convulsive states associated wtih nonketotic hyperglycinemia. This conclusion was recently stated, for example, at an international congress on human genetics.3 We regard this assumption as unwarranted. We have administered valproate to two nonketotic hyperglycinemic patients and monitored glycine levels in their cerebrospinal fluid. It is the elevated CSF glycine which has been postulated to result in the encephalopathy in nonketotic hyperglycinemia.4