Recovery and functional outcomes following olanzapine treatment for bipolar I mania

Authors

  • KN Roy Chengappa,

    1. Western Psychiatric Institute and Clinic, University of Pittsburgh, School of Medicine
    2. Special Studies Center at Mayview State Hospital
    Search for more papers by this author
  • John Hennen,

    1. Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston and Bipolar and Psychotic Disorders Program, McLean Division of Massachusetts General Hospital, Belmont, MA, USA
    Search for more papers by this author
  • Ross J Baldessarini,

    1. Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston and Bipolar and Psychotic Disorders Program, McLean Division of Massachusetts General Hospital, Belmont, MA, USA
    Search for more papers by this author
  • David J Kupfer,

    1. Western Psychiatric Institute and Clinic, University of Pittsburgh, School of Medicine
    Search for more papers by this author
  • Lakshmi N Yatham,

    1. Department of Psychiatry, College of Medicine, University of British Columbia, Vancouver, BC, Canada
    Search for more papers by this author
  • Samuel Gershon,

    1. Western Psychiatric Institute and Clinic, University of Pittsburgh, School of Medicine
    Search for more papers by this author
  • Robert W Baker,

    1. Lilly Research Laboratories, Indianapolis, IN, USA
    Search for more papers by this author
  • Mauricio Tohen

    1. Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston and Bipolar and Psychotic Disorders Program, McLean Division of Massachusetts General Hospital, Belmont, MA, USA
    2. Lilly Research Laboratories, Indianapolis, IN, USA
    Search for more papers by this author

  • These analyses were conducted through an academic-industry partnership, and the data were provided at the level of the individual subjects. Some of the authors (KNRC, JH, RJB, DJK, LNY) have served as consultants to or received research grant support from Lilly Research Laboratories. Furthermore, two of the authors (MT, RWB) are employees of Lilly Research Laboratories. Dr Gershon has no conflicts of interest to disclose with regards to this manuscript. The readers should note that as both editors are authors on this manuscript – key decisions regarding acceptance or rejection were made by senior editorial board members, independent of the editors.

KN Roy Chengappa, MD, FRCPC, Western Psychiatric Institute and Clinic/University of Pittsburgh, School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213-2593, USA.
Fax: 412 246-6116;
e-mail: chengappakn@upmc.edu

Abstract

Background:  Typical experimental categorizations of treatment responses in bipolar disorder (BPD) patients may have limited relationship to clinical recovery or functional status, and there is inadequate research on such clinically important outcomes.

Methods:  We analyzed data from a study of open continuation of olanzapine treatment following a 3-week placebo-controlled trial involving initially hospitalized adult subjects with DSM-IV BP-I mania to estimate rates and times to symptomatic remission (low scores on standardized symptomatic assessments) and clinical recovery (remission sustained ≥8 weeks), associated clinical factors, and functional outcomes.

Results:  During treatment with olanzapine for 27.9 ± 20.1 weeks, symptomatic remission was attained by 70% of subjects, half by 8 weeks (95% CI 6–10) weeks, and later lost by 82% of remitted subjects; remitted (versus non-remitted) subjects had slightly lower baseline clinical global impression scores and greater trial-completion. Sustained clinical recovery was attained by only 40 of 113 (35%) of subjects, half by 36 (95% CI 20–40) weeks, and later lost by 45%. Subjects with above-median (>12) initial Hamilton-Depression rating scale depression scores were half as likely to recover (p = 0.016) and did so much later (36 versus 12 weeks) than those with lower scores. At final assessment, self-rated well being (SF-36 psychosocial functioning scores) improved substantially more among recovered versus non-recovered subjects (mean changes: 87% versus 23%), and two-thirds of recovered subjects remained unemployed-for-pay while half received disability-compensation.

Conclusions:  Clinically meaningful symptomatic remission and recovery in relatively severely ill adult bipolar I manic patients were achieved slowly and sustained by only some patients within an average of 7 months of continuous treatment. These clinically relevant outcomes were worse with relatively high initial dysphoria ratings. Well-being was rated higher by recovered subjects, but their ability to work and live independently were markedly impaired. These findings underscore the emerging view that BPD can often be severe, slow to remit, and disabling, particularly in association with prominent depression-dysphoria symptoms. Improved treatments for BPD are needed, guided by longitudinal assessments of clinically meaningful measures of symptomatic recovery and functional outcome.

Ancillary