title: Valproate augmentation in a subgroup of patients with treatment-resistant unipolar depression.
abstract: OBJECTIVE
  About 50% of patients with unipolar depression suffer from treatment-resistant depression (TRD). Animal studies have suggested potential antidepressant properties of valproate (VPA) possibly due to its implication in epigenetic programming.
  
  
  METHODS
  Fourteen TRD patients (seven males and seven females; age 19-59) received VPA (375-1000 mg/day) in addition to their treatment regimen after previously failing to respond to two or more antidepressant trials and/or different combinations. Clinical response to VPA was investigated prior the treatment (T-0) and after 1 (T-1), 4 (T-4) and 7 (T-7) months of therapy using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI).
  
  
  RESULTS
  Compared to T-0, VPA significantly decreased MADRS score at T-1 (P < 0.001), T-4 (P < 0.001) and T-7 (P < 0.001) (partial η(2)=0.86). Importantly, MADRS score at T-7 (13.6 ± 1.6, mean ± SEM) was closer to the reported value of remission (MADRS <10), and none of the patients relapsed during the observational period. Compared to T-0, VPA also decreased CGI-Severity of illness score at T-1 (p = 0.03), T-4 (p < 0.001) and T-7 (p < 0.001) (partial η(2) = 0.74).
  
  
  CONCLUSIONS
  Antidepressant augmentation with VPA provided substantial clinical improvement and maintenance over a relatively long-term period in a subgroup of patients with severe TRD. VPA thus deserves further exploration in large double-blind clinical trials.
authors.affiliation: a Neurobiological Psychiatry Unit, Department of Psychiatry , McGill University Health Center, McGill University , Montreal , QC , Canada.|b Mood Disorder Clinic, Department of Psychiatry , McGill University Health Center, McGill University , Montreal , QC , Canada.
authors.forename: Maykel F
authors.initials: MF
authors.lastname: Ghabrash
authors.affiliation: a Neurobiological Psychiatry Unit, Department of Psychiatry , McGill University Health Center, McGill University , Montreal , QC , Canada.
authors.forename: Stefano
authors.initials: S
authors.lastname: Comai
authors.affiliation: a Neurobiological Psychiatry Unit, Department of Psychiatry , McGill University Health Center, McGill University , Montreal , QC , Canada.|b Mood Disorder Clinic, Department of Psychiatry , McGill University Health Center, McGill University , Montreal , QC , Canada.
authors.forename: John
authors.initials: J
authors.lastname: Tabaka
authors.affiliation: b Mood Disorder Clinic, Department of Psychiatry , McGill University Health Center, McGill University , Montreal , QC , Canada.
authors.forename: Marie
authors.initials: M
authors.lastname: Saint-Laurent
authors.affiliation: c Sainte-Justine Hospital Research Center & University of Montréal, Montréal, QC, Canada; Department of Psychology, Concordia University, Montreal, QC., Canada; Department of Psychiatry, University of Montréal, and Department of Psychiatry, McGill University , Montréal , QC , Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Booij
authors.affiliation: a Neurobiological Psychiatry Unit, Department of Psychiatry , McGill University Health Center, McGill University , Montreal , QC , Canada.|b Mood Disorder Clinic, Department of Psychiatry , McGill University Health Center, McGill University , Montreal , QC , Canada.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gobbi
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002170:Canada; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D014635:Valproic Acid
keywords: CGI; MADRS; Valproate; antidepressant activity; treatment-resistant depression