LOW-DOSE VALPROATE - A NEW TREATMENT FOR CYCLOTHYMIA, MILD RAPID-CYCLING DISORDERS, AND PREMENSTRUAL-SYNDROME

Background: Valproate has proved useful in the treatment of manic-depr essive and schizoaffective disorders, usually in daily doses above 500 mg with corresponding blood levels in the range established for treat ment of epilepsy (50-100 mug/mL). Since milder bipolar disorders may b e more prevalent than bipolar I disorder, a prospective study was unde rtaken to determine whether lower doses of valproate might be useful f or stabilization of blood cycling in patients having primary diagnoses of cyclothymia or rapid cycling bipolar II disorder. Additionally, op en trials of low-dose valproate were conducted in a small number of wo men complaining of premenstrual syndrome. Method: Over a 3-year period . outpatients with non-menstrually-related rapid cycling who had fulfi lled DSM-111-R criteria for cyclothymia or bipolar II disorder were st arted on open trials of valproate at daily doses of 125 or 250 mg. Dos es were adjusted upward on approximately a monthly basis depending upo n clinical response, and valproate blood levels were obtained. Results : Twenty-six (79%) of 33 patients (15 cyclothymics, 11 bipolar II) rep orted sustained partial or complete stabilization of mood cycling with valproate doses ranging from 125 to 500 mg (mean = 351.0 mg) correspo nding to serum valproate levels (mean = 32.5 mug/mL) substantially bel ow the current recommended range. Cyclothymics required significantly lower doses and blood levels of valproate than patients with bipolar I I disorder for stabilization of mood. Five patients (all bipolar II) f ailed to respond fully to low doses of valproate but improved with hig her doses corresponding to blood levels in the 50 to 100 mug/mL range. Two patients had poor responses to valproate or intolerable side effe cts. In contrast to bipolar spectrum patients. only three (38%) of eig ht women with menstrually related cycling of mood reported good respon ses to low doses of valproate, while five reported no response to valp roate. Conclusion: The findings suggest that (1) low-dose valproate ma y be useful in the treatment of cyclothymia and milder rapid cycling b ipolar disorders and (2) there may be a correlation between the severi ty of bipolar disorder and the blood level of valproate required for s tabilization such that milder forms of bipolar cycling require lower d oses of valproate.