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 developed for the treatment of epilepsy, but also has mood-stabilising, anxiolytic, antimigraine and antinociceptive effects, and has been evaluated in the management of various other disorders, particularly psychiatric conditions. Valproic acid has been shown to be effective in patients with bipolar and schizoaffective disorders, including those resistant to lithium and carbamazepine. Response was achieved in approximately 50 to 70% of patients treated with valproic acid monotherapy for acute 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 noncomparative studies. Moreover, valproic acid appears to be effective in rapid-cycling patients and those with mixed oi dysphoric mania or neurological 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, including panic attacks and aggressive behaviour. Valproic acid was found to provide prophylaxis against migraine with or without aura, and also showed promise in the treatment of acute migraine attacks, and as prophylaxis 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, and neuropathic pain associated with advanced cancer. Valproic acid is generally well tolerated does not induce hepatic drug metabolism and has a low propensity for interactions with psychotropic agents. However; as has been observed with several other antiepileptic drugs, it is teratogenic and call cause elevated hepatic enzyme levels and rare, fatal hepatotoxicity. Weight gain and alopecia are relatively common. Thus, while few comparative data are available, valproic acid has demonstrated considerable potential as a first-line therapy for the management of bipolar or schizoaffective disorder; particularly for patients resistant to, or intolerant of lithium or carbamazepine and those with rapid cycling or mixed mania. It has also shown potential in the treatment of refractory migraine and other types of chronic headache. Further studies are warranted in other psychiatric conditions, including panic attacks, and in severe refractory pain.