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Research News . . . . Topiramate in Bipolar Disorder (cont.) II. Controlled Studies in Acute Mania Four new double-blind, placebo-controlled studies of topiramate monotherapy in acute mania revealed that topiramate does not possess acute antimanic efficacy, whereas the active comparator in two of these studies—lithium—was effective. This data raises questions about mood stabilization, because most drugs that are mood stabilizers are also antimanic drugs (perhaps with the exception of lamotrigine). III. Open Clinical Studies and Case Reports One of the first studies of topiramate in mood disorders was by Marcotte (1998).3 In this retrospective chart review, he found that in 58 patients with diagnosed psychiatric disorders (44 with rapid cycling bipolar disorder) who took adjunctive topiramate, 36 (62%) showed moderate to marked improvement, usually within days or weeks (23 [52%] of 44 patients with rapid cycling bipolar disorder improved). At least 15 other open-label studies have been published on adjunctive topiramate in mood disorders, all of which showing a good rate of moderate to marked response. (Click here to view topiramate table in Adobe Acrobat *.pdf form). In 2000, McElroy et al.4 evaluated the response to adjunctive topiramate in 56 outpatients with bipolar I (n=43), bipolar II (n=11), or schizoaffective, bipolar type (n=2). Of the 30 patients who were treated for manic symptoms at 10 weeks, 19 (63%) showed much or very much improvement; of the initially depressed patients, only 3 (27%) of 11 showed much or very much improvement at 10 weeks, however. Of the 37 patients who continued open maintenance treatment with adjunctive topiramate (for an average of 294.6 days), the response rates were 12 (55%) of 22 improved in mania, but only 1 (9%) of 11 improved when treated for acute depression. The dosage of topiramate ranged from 25-1200 mg/day, with an average of 193.2 mg/day at 10 weeks, and 425 mg/day for those on the drug at one year. Patients lost an average of 1.7% of weight after 10 weeks, 6.2% at one year, and 4.9% at last observation (all patients). Grunze et al. (2001)5 conducted an open (non-blind) trial of topiramate in 11 manic patients in an on (drug)-off (drug)-on trial in Germany. After 10 days, 7 (64%) of 11 patients improved on topiramate; one patient worsened and dropped out. When patients discontinued topiramate during the "off" phase, 7 (70%) of the remaining 10 patients worsened, and another patient dropped out. After re-introducing topiramate, 8 (89%) of the 9 remaining patients improved significantly. This study design, in which the rater is blinded to the "off" period, provides stronger evidence of the efficacy of adjunctive topiramate than other open trial designs. 3 Marcotte D (1998). Use of topiramate, a new anti-epileptic as a mood stabilizer. J Affect Disord 50: 245-251. 4 McElroy SL, Suppes T, Keck PE Jr, Frye MA, Denicoff KD, Altshuler LL, Brown ES, Nolen WA, Kupka RW, Rochussen J, Leverich GS, Post RM (2000). Open-label adjunctive topiramate in the treatment of bipolar disorders. Biol Psychiatry 47: 1025-1033. 5 Grunze HCR, Normann C, Langosch J, Schaefer M, Amann B, Sterr A, Schloesseer S, Kleindienst N, Walden J (2001). Antimanic efficacy of topiramate in 11 patients in an open trial with an on-off-on design. J Clin Psychiatry 62: 464-468. Click here to go to Ortho-McNeil Pharmaceutical Topiramate website Click here to see table of topiramate studies in mood disorders |