VALPROIC ACID - A REVIEW OF ITS PHARMACOLOGY AND THERAPEUTIC POTENTIAL IN INDICATIONS OTHER THAN EPILEPSY

Valproic acid, a simple branched-chain fatty acid, was originally deve loped for the treatment of epilepsy, but also has mood-stabilising, an xiolytic, antimigraine and antinociceptive effects, and has been evalu ated in the management of various other disorders, particularly psychi atric conditions. Valproic acid has been shown to be effective in pati ents with bipolar and schizoaffective disorders, including those resis tant to lithium and carbamazepine. Response was achieved in approximat ely 50 to 70% of patients treated with valproic acid monotherapy for a cute manic episodes in noncomparative and placebo-controlled studies. Long term prophplaxis against recurrent manic and depressive episodes has been demonstrated in approximately 65 to 70% of patients receiving the drug as monotherapy or in combination with other drugs in noncomp arative studies. Moreover, valproic acid appears to be effective in ra pid-cycling patients and those with mixed oi dysphoric mania or neurol ogical abnormalities, who tend to respond poorly to lithium. Evidence from preliminary studies and case reports suggests that valproic acid may prove useful for management of other psychiatric conditions, inclu ding panic attacks and aggressive behaviour.Valproic acid was found to provide prophylaxis against migraine with or without aura, and also s howed promise in the treatment of acute migraine attacks, and as proph ylaxis against refactory chronic daily headache. Preliminary findings suggest that valproic acid may be of value in the management of severe refractory pain, including trigeminal neuralgia, lancinating pain, an d neuropathic pain associated with advanced cancer. Valproic acid is g enerally well tolerated does not induce hepatic drug metabolism and ha s a low propensity for interactions with psychotropic agents. However; as has been observed with several other antiepileptic drugs, it is te ratogenic and call cause elevated hepatic enzyme levels and rare, fata l hepatotoxicity. Weight gain and alopecia are relatively common. Thus , while few comparative data are available, valproic acid has demonstr ated considerable potential as a first-line therapy for the management of bipolar or schizoaffective disorder; particularly for patients res istant to, or intolerant of lithium or carbamazepine and those with ra pid cycling or mixed mania. It has also shown potential in the treatme nt of refractory migraine and other types of chronic headache. Further studies are warranted in other psychiatric conditions, including pani c attacks, and in severe refractory pain.