title: Incidence and time course of subsyndromal symptoms in patients with bipolar I disorder: an evaluation of 2 placebo-controlled maintenance trials.
abstract: BACKGROUND
  Subsyndromal symptoms in bipolar disorder can cause significant functional impairment and are associated with relapse.
  
  
  METHODS
  In this post hoc analysis from 2 randomized, double-blind, 18-month, placebo-controlled maintenance trials for bipolar I disorder (both trials were conducted between August 1997 and August 2001 and used DSM-IV criteria), the incidence, time course, and impact of pharmacotherapy on subsyndromal symptoms were examined.
  
  
  RESULTS
  Subsyndromal symptoms occurred in approximately 25% of all visits. Compared with placebo (54.8%), a significantly higher mean percentage of visits in remission were observed with lamotrigine treatment (63.0%, p = .020) but not with lithium treatment (60.0%, p = .165). The median time to onset of subsyndromal symptoms for lamotrigine (N = 223), lithium (N = 164), and placebo (N = 188) was 15, 15, and 9 days, respectively. Compared with placebo, both lamotrigine and lithium significantly delayed the time from randomization to onset of subsyndromal symptoms (p = .046, lamotrigine vs. placebo; p = .033, lithium vs. placebo; p = .763, lamotrigine vs. lithium) and the time from onset of subsyndromal symptoms to subsequent mood episode (p = .037, lamotrigine vs. placebo; p = .023, lithium vs. placebo; p = .845, lamotrigine vs. lithium). Agreement between the polarities of the first-observed subsyndromal symptom and subsequent intervention for mood episode was statistically significant (p < .001).
  
  
  CONCLUSIONS
  Subsyndromal symptoms are common during maintenance treatment and appear to be associated with relapse into an episode of the same polarity. Both lithium and lamotrigine delayed the onset of subsyndromal symptoms and the time from onset of subsyndromal symptoms to subsequent relapse. Further study to assess whether treatment intervention can minimize subsyndromal symptoms or prevent relapse is encouraged.
authors.affiliation: Mood Disorders Research Program, University of California at Los Angeles, USA. mfrye@mayo.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.forename: Lakshmi N
authors.initials: LN
authors.lastname: Yatham
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bowden
authors.forename: Terence A
authors.initials: TA
authors.lastname: Ketter
authors.forename: Trisha
authors.initials: T
authors.lastname: Suppes
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Adams
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Thompson
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000145:classification / Q000188:drug therapy* / Q000453:epidemiology*; D015897:Comorbidity; D003863:Depression / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D000077213:Lamotrigine; D018020:Lithium Compounds / Q000627:therapeutic use*; D019964:Mood Disorders / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use*
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds; D014227:Triazines; D000077213:Lamotrigine