title: Long-term safety and efficacy of armodafinil in bipolar depression: A 6-month open-label extension study.
abstract: BACKGROUND
  Safe/well-tolerated treatments for bipolar I depression remain limited. We assessed safety/tolerability of adjunctive open-label armodafinil, a wakefulness-promoting agent evaluated in 3 acute, controlled efficacy studies with variable efficacy results.
  
  
  METHODS
  Completers of three 8-week, double-blind, placebo-controlled adjunctive armodafinil studies (150-200 mg/day added to ongoing stable maintenance doses of 1 or 2 protocol-defined mood stabilizers) in bipolar I depression could enter this 6-month, open-label extension study. Objectives included evaluation of safety/tolerability (primary) and efficacy (secondary).
  
  
  RESULTS
  867 patients enrolled; 863 received ≥1 dose of armodafinil and 506 (58%) completed the 6-month study. Headache, insomnia, and anxiety were the most common adverse events (AEs) reported, whereas akathisia, nausea, sedation/somnolence, and weight increase were uncommon. Mean measures assessing emergence of mania, anxiety, insomnia, or suicidality showed no worsening. Discontinuations due to AEs occurred in 57 (7%) patients. Serious AEs occurred in 27 (3%) patients and were considered treatment-related in 8 (1%) patients. Depressive symptoms improved over the 6 months, as did patient functioning.
  
  
  CONCLUSIONS
  Lack of placebo control.
  
  
  CONCLUSIONS
  Adjunctive armodafinil was generally safe and well tolerated over 6 months of open-label treatment at 150-200 mg/day when taken with protocol-defined mood stabilizers for bipolar I depression. This 6-month open-label study suggested that armodafinil augmentation of bipolar maintenance therapies may have a favorable risk profile and may improve depressive symptoms in some patients with bipolar I depression.
authors.affiliation: Stanford University School of Medicine, Stanford, CA, USA. Electronic address: tketter@stanford.edu.
authors.forename: Terence A
authors.initials: TA
authors.lastname: Ketter
authors.affiliation: Teva Pharmaceuticals, Frazer, PA, USA.
authors.forename: Jess
authors.initials: J
authors.lastname: Amchin
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.affiliation: Teva Pharmaceuticals, Frazer, PA, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gross
mesh_terms: D000328:Adult; D000368:Aged; D001007:Anxiety / Q000139:chemically induced; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D016896:Treatment Outcome; D064690:Wakefulness-Promoting Agents / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil
keywords: Armodafinil; Bipolar I disorder; Bipolar depression; Long-term safety; Wakefulness