title: Course sequences in bipolar disorder: depressions preceding or following manias or hypomanias.
abstract: BACKGROUND
  Inferior response to lithium treatment has been reported in bipolar disorder (BD) patients with mania or hypomania following episodes of major depression (DMI) versus preceding depression (MDI), with intervening euthymic periods. However, additional characteristics of BD course-patterns require further assessment.
  
  
  METHODS
  We reviewed computerized clinical records and life-charts of 855 DSM-IV-TR BD-I or -II patients assessed and followed at mood-disorder centers in Cagliari or Rome to characterize their predominant course-sequences.
  
  
  RESULTS
  Morbidity over an average of 9.5 cycles in 18 years was characterized for sequencing of illness-episodes and euthymic intervals. Prevalent sequences included: major depression-hypomania (15.0%), mania-major depression (14.6%), major depression-mania (11.6%), and rapid-cycling (9.6%). Among subjects grouped by course-sequences (based on mania, mixed-states, or hypomania and major or minor depression), depression-before-[hypo]mania (DMI) cases were more likely to be women, diagnosed BD-II, have first-episodes of depressive or anxiety disorder, spend more time ill in depression, and benefit less with long-term mood-stabilizing treatments than with the opposite pattern (MDI). MDI patients were more likely to have substance-abuse and receive long-term mood-stabilizer treatments. Meta-analysis of 5 previous reports plus present findings found inferior treatment-response in DMI vs. MDI cases at a pooled risk-difference of 29% [CI: 18-40%] (p<0.0001).
  
  
  CONCLUSIONS
  Some data were retrospective and subject to recall bias, and treatment was clinical (non-randomized).
  
  
  CONCLUSIONS
  The DMI course was strongly associated with first-episode depression or anxiety, excess depressive morbidity, and inferior treatment response, especially for depression.
authors.affiliation: Lucio Bini Mood Disorder Centers, Rome and Cagliari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Koukopoulos
authors.forename: D
authors.initials: D
authors.lastname: Reginaldi
authors.forename: L
authors.initials: L
authors.lastname: Tondo
authors.forename: C
authors.initials: C
authors.lastname: Visioli
authors.forename: R J
authors.initials: RJ
authors.lastname: Baldessarini
mesh_terms: D001714:Bipolar Disorder / Q000188:drug therapy / Q000523:psychology*; D003865:Major Depressive Disorder / Q000523:psychology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
keywords: Bipolar disorder; Course sequence; Depression; Mania