That 20% of the patients with bipolar disorder could not be stabilized while taking open-label divalproex is not particularly surprising. The response rate of 80% with open-label divalproex was substantial, however, and similar to what has been found in other open-label studies (1). The 14-day treatment with mixed amphetamine salts and placebo was long enough to establish clinical statistical significance. Most patients (23 of 29) did elect open treatment with mixed amphetamine salts for 6 additional weeks. We made no claims of efficacy for open divalproex treatment, only that it was associated with a benefit in this group. The elicited and spontaneously reported side effects in the entire trial were very low, perhaps because we did not aggressively "load" the divalproex and we used relatively low doses of mixed amphetamine salts in the crossover study. In the open extension (when the dosing of mixed amphetamine salts was not limited), the average dose remained low, at 14.5 mg/day, suggesting that this relatively low dose was clinically useful.