Thus, the clinical research on the kindling hypothesis may be interpreted as buy MDV3100 supportive of the hypothesis, albeit in a limited and not yet definitive manner. Patterns of mood-stabilizing treatment Research on outcome in bipolar disorder has led to an interest in new treatments for the illness. In the last decade, anticonvulsants have assumed a well-deserved role in the treatment of bipolar

disorder. Initial studies focused on lithium-resistant patients, especially rapid cycling, mixed states, and/or concurrent substance abuse. Recently, some authors have advocated anticonvulsants as treatments of first choice. Caution Inhibitors,research,lifescience,medical is in order here. The long track record of lithium provides a firm knowledge of risks and benefits. For example, Inhibitors,research,lifescience,medical lithium’s impact on preventing suicide is established. A recent review of 28 studies involving over 150 suicides indicates a sixfold reduction in suicide with lithium treatment of bipolar disorder compared to no treatment.52 The serotonergic effects of lithium implicated in the neurobiology of suicide may help explain these data.53 A recent Inhibitors,research,lifescience,medical large prospective

2½-year randomized study comparing lithium with carbamazepine found 9 suicide events in the carbamazepine group (5 deaths, 4 severe attempts) versus none for the lithium group (P<0.02).54 Meanwhile, a 1-year multisite study of divalproex prophylaxis could not establish a significant advantage over placebo.55 While this negative finding may stem from inadequate statistical power since severely ill patients were excluded, nonetheless, the lack of a robust prophylactic effect Inhibitors,research,lifescience,medical in those patients studied suggests caution. In an earlier multisite study comparing the acute antirnanic effects

of divalproex, lithium, and placebo, those patients with a history of prior response to lithium Inhibitors,research,lifescience,medical had a robust antirnanic response to its readminstration, but the divalproex response in this group was only 27 %. On the other hand, those with a prior history of nonresponse to lithium showed a relatively Rutecarpine high rate of response to the anticonvulsant, suggesting that there may be two substantially separable antirnanic response patterns. Since antirnanic response may predict prophylactic efficacy,39,56-58 this highlights the danger of discontinuing lithium treatment in responders to it. Also, lithium discontinuation (especially when abrupt) promotes rapid relapse.59,60 The possibility of lithium withdrawal-induced treatment refractoriness has also been raised,61 though not settled.62 The antidepressant problem Not surprisingly, patients with bipolar disorder often are more aware of depression and its concomitant symptoms than they are of mood elevation.