Lithium adds clinically and statistically significant benefit to haloperidol treatment of mania (15) as does carbamazepine (16) and phenytoin (17). Such an "add-on" design is consistent with clinical practice and makes sense since dopamine blockers and mood stabilizers probably work by different mechanisms in mania. Valproate is typically used clinically in acute mania as an add-on to neuroleptics as well. Three positive studies published in excellent journals (15-17) from our group using this design are probably better than formal power analysis, which depends on a range of assumptions that are collapsible into the experience of our three studies. Because the prior probability of an effect of valnoctamide is lower than that of the above well-known compounds, we suggest recruitment of 80 patients over 36 months to adequately power this study rather than the 40 patients in each of our previous studies. Since valnoctamide is no longer patented, orphan drug procedures or a use patent of the type granted to Abbott for divalproex sodium will be necessary to make this drug available for bipolar patients at risk for pregnancy in the future. An adequately powered study is therefore important at this stage.