title: Preliminary observations on the effectiveness of levetiracetam in the open adjunctive treatment of refractory bipolar disorder.
abstract: OBJECTIVE
  Levetiracetam is a recently approved, well-tolerated anticonvulsant with a unique mechanism of action yielding efficacy in treatment-refractory seizure disorders and positive effects in an animal model of mania. Given the effectiveness of a range of other anticonvulsants in bipolar disorder, we sought to evaluate levetiracetam in patients with treatment-resistant illness.
  
  
  METHODS
  Thirty-four patients received 500 to 1000 mg of levetiracetam titrated to a target dose of 2000 mg/day (maximum dose = 3000 mg/day) as open, adjunctive treatment for clinically significant symptoms of depression (N = 13), mania (N = 7), or cycling (N = 14) despite ongoing treatment with mood stabilizers. Inventory for Depressive Symptomatology-Clinician version (IDS-C), Young Mania Rating Scale (YMRS), and Clinical Global Impressions scale for use in Bipolar Illness ratings were completed at each visit for 8 weeks, and partial responders were offered continuation treatment. Data were collected from July 2001 to December 2002.
  
  
  RESULTS
  Five of 16 (31%; 13 depressed, 3 cycling) patients with initial depressive symptoms met the criterion for remission (IDS-C score of < or = 13) at last observation. All of these patients were less severely ill at baseline, whereas none of those more severely depressed at baseline responded. The majority of the 16 patients (7 manic, 9 cycling) with manic symptoms at baseline showed improvement in the YMRS in the first 2 weeks. While 7 of the 16 (44%) patients met the criterion for manic response and remission at last observation, 4 showed intervening periods of moderate to marked exacerbation. Levetiracetam was weight neutral.
  
  
  CONCLUSIONS
  Other pilot trials should explore possible areas of psychotropic action of levetiracetam prior to the conduct of more controlled clinical trials.
authors.affiliation: Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. Robert.Post@nih.gov
authors.forename: Robert M
authors.initials: RM
authors.lastname: Post
authors.forename: Lori L
authors.initials: LL
authors.lastname: Altshuler
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.forename: Trisha
authors.initials: T
authors.lastname: Suppes
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.forename: Paul E
authors.initials: PE
authors.lastname: Keck
authors.forename: Gabriele S
authors.initials: GS
authors.lastname: Leverich
authors.forename: Ralph
authors.initials: R
authors.lastname: Kupka
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.forename: Jorg
authors.initials: J
authors.lastname: Walden
authors.forename: Heinz
authors.initials: H
authors.lastname: Grunze
mesh_terms: D000328:Adult; D000553:Ambulatory Care; D000927:Anticonvulsants / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008137:Longitudinal Studies; D008297:Male; D010865:Pilot Projects; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011145:Polyvinyls; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; D000077287:Levetiracetam; D010889:Piracetam