title: DSM-5 mixed specifier for manic episodes: evaluating the effect of depressive features on severity and treatment outcome using asenapine clinical trial data.
abstract: BACKGROUND
  To describe the frequency of mixed specifier as proposed in DSM-5 in bipolar I patients with manic episodes, and to evaluate the effect of mixed specifier on symptom severity and treatment outcome.
  
  
  METHODS
  This post-hoc analysis used proxies for DSM-5 mixed features specifier by using MADRS or PANSS items.
  
  
  RESULTS
  Of the 960 patients analysed, 34%, 18% and 4.3% of patients, respectively, had ≥3 depressive features with mild (score ≥1 for MADRS items and ≥2 for PANSS item), moderate (score ≥2 MADRS, ≥3 PANSS) and severe (score ≥3 MADRS, ≥4 PANSS) symptoms. In patients with ≥3 depressive features and independent of treatment: MADRS remission (score ≤12) rate decreased with increasing severity (61-43%) and YMRS remission (score ≤12) was similar for mild and moderate patients (36-37%), but higher for severe (54%). In asenapine-treated patients, the MADRS remission rate was stable regardless of baseline depressive symptom severity (range 64-67%), whereas remission decreased with increasing severity with olanzapine (63-38%) and placebo (49-25%). Reduction in YMRS was significantly greater for asenapine compared with placebo at day 2 across the 3 severity cut-offs and continued to decrease throughout the treatment period. The difference between olanzapine and placebo was statistically significant in mild and moderate patients.
  
  
  CONCLUSIONS
  Results are from post-hoc analyses.
  
  
  CONCLUSIONS
  These analyses support the validity of proposed DSM-5 criteria. They confirm that depressive features are frequent in bipolar patients with manic episodes. With increasing baseline severity of depressive features, treatment outcome was poorer with olanzapine and placebo, but remained stable with asenapine.
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, ON, Canada M5T 2S8.
authors.forename: R S
authors.initials: RS
authors.lastname: McIntyre
authors.forename: M
authors.initials: M
authors.lastname: Tohen
authors.forename: M
authors.initials: M
authors.lastname: Berk
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: E
authors.initials: E
authors.lastname: Weiller
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000145:classification / Q000175:diagnosis* / Q000188:drug therapy*; D003863:Depression; D039721:Diagnostic and Statistical Manual of Mental Disorders; D003986:Dibenzocycloheptenes; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D000077152:Olanzapine; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D001569:Benzodiazepines; C522667:asenapine; D000077152:Olanzapine
keywords: Asenapine; Bipolar I disorder; DSM-5 mixed specifier; Depressive features; Manic episode; Olanzapine