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Cited by 103Bipolar Disorder and TreatmentSchizophrenia research and treatmentPersonality Disorders and Psychopathology

Recurrence rates in bipolar disorder: Systematic comparison of long-term prospective, naturalistic studies versus randomized controlled trials

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Vázquez, Gustavo H., Holtzman, Jessica N., Lolich, María, Ketter, Terence A., Baldessarini, Ross J.·2015·European Neuropsychopharmacology
DOI 10.1016/j.euroneuro.2015.07.013
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Abstract

Bipolar disorder (BD) is a recurrent, lifelong illness with high risks of disability and excess mortality. Despite many treatment options with demonstrated short-term efficacy, evidence concerning long-term treatment effectiveness in BD remains limited and the relative value of naturalistic studies versus randomized, controlled trials (RCTs) in its assessment, uncertain. Systematic computer-searching yielded 10 naturalistic studies and 15 RCTs suitable for analysis of recurrence rates and their association with treatments and selected clinical factors. In naturalistic studies (3904 BD subjects, 53.3% women, 85.8% BD-I, mean onset age 29.1, followed up to 2.1 years), the pooled recurrence rate was 55.2% (26.3%/year). In RCTs (4828 subjects, 50.9% women, 96.0% BD-I, mean onset age 23.1, followed up to 1.9 years), the pooled recurrence rate was 39.3% (21.9%/year) with mood-stabilizing drug-treatment versus 60.6% (31.3%/year) with placebo; drug-versus-placebo outcomes favored antipsychotics over lithium, and disfavor an approved anticonvulsant. Depressive episode-polarity increased from 27.7% at intake to 52.0% at first-recurrence (p<0.0001). Recurrence rate (%/year) did not differ by study-type, was greater with younger onset and rapid-cycling, and paradoxically declined with longer observation. In short, recurrences of major affective episodes up to two years during putative mood-stabilizing treatment of BD patients in prospective, naturalistic studies and RCTs were substantial and similar (26.3 vs. 21.9%/year). Episode-polarity shifted strongly toward depressive first-recurrences. These findings support the value of naturalistic studies to complement long-term RCTs, and add to indications that control of depression in BD remains particularly unsatisfactory.

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  1. [3]3. Baldessarini, R.J., 2013. Chemotherapy in Psychhiatry, third ed. Springer Press, New York.

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Authors
Vázquez, G. H., Holtzman, J. N., Lolich, M., Ketter, T. A., & Baldessarini, R. J.
Affiliations
  • McLean Hospital (US)
  • Stanford Medicine (US)
  • University of Palermo (AR)
  • Harvard University (US)
Corresponding author
Vázquez, Gustavo H.
ORCID
Venue
European Neuropsychopharmacology
Publisher
Elsevier BV
Published
2015-10
Volume
25
Issue
10
Pages
1501-1512
ISSN
0924-977X (ISSN-L)
DOI
10.1016/j.euroneuro.2015.07.013
OpenAlex
W1960912647
Cited by
102
References
53
Citations by year
2026: 7 · 2025: 12 · 2024: 12 · 2023: 12 · 2022: 8 · 2021: 11 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 15 · 2016: 4
FWCI
7.30
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • European Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • CONICET Digital (CONICET) (submittedVersion, cc-by-nc-nd)
Funders
  • Bruce J. Anderson Foundation
  • McLean Private Donors Research Fund (RJB)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Social Sciences › Psychology › Clinical Psychology › Personality Disorders and Psychopathology
Keywords
bipolar disorder, recurrence rate, naturalistic study, randomized controlled trials, mood stabilizers, lithium, antipsychotic drugs, antiepileptic drugs, rapid cycling bipolar disorder, age of onset, long-term treatment effectiveness
MeSH terms
Bipolar Disorder, Humans, Recurrence, Randomized Controlled Trials as Topic, Treatment Outcome

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