conclusive controlled studies are missing Phcnytoin showed some

conclusive controlled studies are missing. Phcnytoin showed some efficacy in a comparator study against fluoxetine,147 but not in an BI 6727 augmentation study in SSRI nonresponders.148 Bipolar disorder The classical psychiatric indication for antiepileptic drugs is clearly bipolar disorder. Licensed in this indication or at least, used with good evidence are valproate, carbamazepine, and lamotrigine, but phenytoin, oxcarbazepine, levetiracetam, topiramate, zonisamide, and gabapentin may also be beneficial in some, yet insufficiently characterized patients. Carbamazepine has proven antimanic149 and prophylactic efficacy,150 and has been traditionally Inhibitors,research,lifescience,medical used in patients who were not sufficiently

responding to lithium. Comparing the prophylactic efficacy of carbamazepine against, lithium, the two most recent studies suggest superiority of lithium treatment.151-152 However, carbamazepine appeared in the MAP study to be the better alternative for atypical manifestations of bipolar disorder, such as rapid cycling course, frequent recurrence of dysphoric Inhibitors,research,lifescience,medical or psychotic mania, or other comorbid psychiatric or neurological conditions.153 In patients not sufficiently responsive to lithium, addition of carbamazepine can greatly enhance prophylactic efficacy as shown in a large controlled study.154 Valproate has nowadays established itself as a first-line treatment of acute mania.

Superiority Inhibitors,research,lifescience,medical over placebo has been shown in double-blind controlled monotherapy and add-on studies.155-158 Compared with lithium, valproate was especially effective in conditions less responsive to lithium such as mixed states and a rapid cycling course.159 For bipolar depression, one small placebo-controlled study Inhibitors,research,lifescience,medical has been published, showing significant Inhibitors,research,lifescience,medical effects.160 The so-far only large-scale randomized maintenance study comparing valproate against placebo and lithium could not prove efficacy either for valproate or lithium for the primary outcome criterion (time to any mood episode). Further analysis revealed that this was mainly due to a selection bias, as patients having a benign

course of the illness were overrepresented in the study. Looking for secondary outcome parameters, however, clinically AV-951 useful information was detected, eg, valproate was significantly better than placebo in preventing new depressive episodes. In addition, patients who were previously responsive to valproate when treated for an acute episode also performed better when randomized to valproate maintenance treatment compared with when randomized to lithium or placebo. However, reanalyzing this study together with other, smaller studies, a meta-analysis was able to support the prophylactic efficacy of valproate.150 It is of note that phenytoin-exerted antimanic and prophylactic properties, but no antidepressant action, has also been found in randomized, placebo-controlled studies.

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