title: Open-label adjunctive zonisamide in the treatment of bipolar disorders: a prospective trial.
abstract: BACKGROUND
  The response of 62 outpatients with DSM-IV bipolar disorders to open-label adjunctive zonisamide was evaluated in a prospective 8-week acute trial, followed by a 48-week continuation trial, conducted from June 2001 through May 2002.
  
  
  METHODS
  During the acute trial, response to zonisamide was assessed weekly for the first 4 weeks and every 2 weeks for the second 4 weeks with the Clinical Global Impressions scale modified for bipolar illness (CGI-BP), the Young Mania Rating Scale (YMRS), and the Inventory for Depressive Symptomatology (IDS). During the continuation trial, patients were assessed with these scales every 4 weeks. Patients' weights and side effects were also evaluated. Outcome measures were analyzed with repeated-measures analyses of variance.
  
  
  RESULTS
  Patients with manic symptoms at study entry (N = 34) displayed significant reductions in CGI-BP-Mania Severity and YMRS scores in the acute and continuation (N = 19) trials (p values < .0001 and < .001, respectively). Patients with depressive symptoms at study entry (N = 22) showed significant decreases in CGI-BP-Depression Severity and IDS scores in the acute trial (p values < .001 and < .05, respectively), but only 9 patients entered the continuation trial. Among these 9 patients, maintenance of anti-depressant response was mostly maintained. Initially euthymic patients (N = 6) showed no change in any rating scale scores acutely, but 2 of 4 patients who entered the continuation trial developed depressive symptoms. The 62 patients as a group showed significant weight loss in both trials (p values < .001). However, 20 patients (32%) discontinued zonisamide for worsening mood symptoms.
  
  
  CONCLUSIONS
  Adjunctive zonisamide was associated with beneficial effects on mood and body weight in some patients with bipolar disorders, but was also associated with a high discontinuation rate due to worsening mood symptoms. Double-blind, placebo-controlled studies are necessary to determine zonisamide's thymoleptic properties, if any, in bipolar disorders.
authors.affiliation: Psychopharmacology Research Program, Department of Psychiatry, PO Box 670559, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA. susan.mcelroy@uc.edu
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.forename: Trisha
authors.initials: T
authors.lastname: Suppes
authors.forename: Paul E
authors.initials: PE
authors.lastname: Keck
authors.forename: David
authors.initials: D
authors.lastname: Black
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.forename: Lori L
authors.initials: LL
authors.lastname: Altshuler
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
authors.forename: Ralph W
authors.initials: RW
authors.lastname: Kupka
authors.forename: Gabriele S
authors.initials: GS
authors.lastname: Leverich
authors.forename: Jorg
authors.initials: J
authors.lastname: Walden
authors.forename: Heinz
authors.initials: H
authors.lastname: Grunze
authors.forename: Robert M
authors.initials: RM
authors.lastname: Post
mesh_terms: D000328:Adult; D000553:Ambulatory Care; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010352:Patient Dropouts; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D011619:Psychotropic Drugs; D000078305:Zonisamide