THE PLACE OF ANTICONVULSANT THERAPY IN BIPOLAR ILLNESS

With the increasing recognition of lithium's inadequacy as an acute an d prophylactic treatment for many patients and subtypes of bipolar ill ness, the search for alternative agents has centered around the mood s tabilizing anticonvulsants carbamazepine and valproate. In many instan ces, these drugs are effective alone or in combination with lithium in those patients less responsive to lithium monotherapy, including thos e with greater numbers of prior episodes, rapid-cycling, dysphoric man ia, co-morbid substance abuse or other associated medical problems, an d patients without a family history of bipolar illness in first-degree relatives. Nineteen double-blind studies utilizing a variety of desig ns suggest that carbamazepine, or its keto-congener oxcarbazepine, is effective in acute mania; six controlled studies report evidence of th e efficacy of valproate in the treatment of acute mania as well. Fourt een controlled or partially controlled studies of prophylaxis suggest carbamazepine is also effective in preventing both manic and depressiv e episodes. Valproate prophylaxis data, although based entirely on unc ontrolled studies, appear equally promising. Thus, both drugs are wide ly used and are now recognized as major therapeutic tools for lithium- nonresponsive bipolar illness. The high-potency anticonvulsant benzodi azepines, clonazepam and lorazepam, are used adjunctively with lithium or the anticonvulsant mood stabilizers as substitutes or alternatives for neuroleptics in the treatment of manic breakthroughs. Preliminary controlled clinical trials suggest that the calcium channel blockers may have antimanic or mood-stabilizing effects in a subgroup of patien ts. A new series of anticonvulsants has just been FDA-approved and war rant clinical trials to determine their efficacy in acute and long-ter m treatment of mania and depression. Systematic exploration of the opt imal use of lithium and the mood-stabilizing anticonvulsants alone and in combination, as well as with adjunctive antidepressants, is now re quired so that more definitive treatment recommendations for different types and stages of bipolar illness can be more strongly evidence bas ed.