Skip to main content

Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial.

Image
By
Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial.
BACKGROUND:
Lithium carbonate and valproate semisodium are both recommended as monotherapy for prevention of relapse in bipolar disorder, but are not individually fully effective in many patients. If combination therapy with both agents is better than monotherapy, many relapses and consequent disability could be avoided. We aimed to establish whether lithium plus valproate was better than monotherapy with either drug alone for relapse prevention in bipolar I disorder.
METHODS:
330 patients aged 16 years and older with bipolar I disorder from 41 sites in the UK, France, USA, and Italy were randomly allocated to open-label lithium monotherapy (plasma concentration 0.4-1.0 mmol/L, n=110), valproate monotherapy (750-1250 mg, n=110), or both agents in combination (n=110), after an active run-in of 4-8 weeks on the combination. Randomisation was by computer program, and investigators and participants were informed of treatment allocation. All outcome events were considered by the trial management team, who were masked to treatment assignment. Participants were followed up for up to 24 months. The primary outcome was initiation of new intervention for an emergent mood episode, which was compared between groups by Cox regression. Analysis was by intention to treat. This study is registered, number ISRCTN 55261332.
FINDINGS:
59 (54%) of 110 people in the combination therapy group, 65 (59%) of 110 in the lithium group, and 76 (69%) of 110 in the valproate group had a primary outcome event during follow-up. Hazard ratios for the primary outcome were 0.59 (95% CI 0.42-0.83, p=0.0023) for combination therapy versus valproate, 0.82 (0.58-1.17, p=0.27) for combination therapy versus lithium, and 0.71 (0.51-1.00, p=0.0472) for lithium versus valproate. 16 participants had serious adverse events after randomisation: seven receiving valproate monotherapy (three deaths); five lithium monotherapy (two deaths); and four combination therapy (one death).

INTERPRETATION:
For people with bipolar I disorder, for whom long-term therapy is clinically indicated, both combination therapy with lithium plus valproate and lithium monotherapy are more likely to prevent relapse than is valproate monotherapy. This benefit seems to be irrespective of baseline severity of illness and is maintained for up to 2 years. BALANCE could neither reliably confirm nor refute a benefit of combination therapy compared with lithium monotherapy.
FUNDING:
Stanley Medical Research Institute; Sanofi-Aventis.

Copyright 2010 Elsevier Ltd. All rights reserved.

Full Text

Comments

Post a Comment

Your Thoughts?

Popular posts from this blog

ADVOKATE: A Mnemonic Tool for the Assessment of Eyewitness Evidence

By
ADVOKATE: A Mnemonic Tool for Assessment of Eyewitness Evidence A tool for assessing eyewitness  ADVOKATE is a tool designed to assess eyewitness evidence and how much it is reliable. It requires the user to respond to several statements/questions. Forensic psychologists, police or investigative officer can do it. The mnemonic ADVOKATE stands for: A = amount of time under observation (event and act) D = distance from suspect V = visibility (night-day, lighting) O = obstruction to the view of the witness K = known or seen before when and where (suspect) A = any special reason for remembering the subject T = time-lapse (how long has it been since witness saw suspect) E = error or material discrepancy between the description given first or any subsequent accounts by a witness.  Working with suspects (college.police.uk)
Post a Comment
Read more

ICD-11 Criteria for Attention Deficit Hyperactivity Disorder (ADHD) 6A05

By
ICD-11 Criteria for Attention Deficit Hyperactivity Disorder (ADHD) 6A05 Attention deficit hyperactivity disorder is characterised by a persistent pattern (at least 6 months) of inattention and/or hyperactivity-impulsivity that has a direct negative impact on academic, occupational, or social functioning. There is evidence of significant inattention and/or hyperactivity-impulsivity symptoms prior to age 12, typically by early to mid-childhood, though some individuals may first come to clinical attention later. The degree of inattention and hyperactivity-impulsivity is outside the limits of normal variation expected for age and level of intellectual functioning. Inattention refers to significant difficulty in sustaining attention to tasks that do not provide a high level of stimulation or frequent rewards, distractibility and problems with organisation. Hyperactivity refers to excessive motor activity and difficulties with remaining still, most evident in structured situations that re...
Post a Comment
Read more

ICD-11 Criteria for Depression (Recurrent Depressive Disorder) 6A71

By
ICD-11 Criteria for Depression (Recurrent Depressive Disorder) 6A71 Recurrent depressive disorder is characterised by a history or at least two depressive episodes separated by at least several months without significant mood disturbance. A depressive episode is characterised by a period of depressed mood or diminished interest in activities occurring most of the day, nearly every day during a period lasting at least two weeks accompanied by other symptoms such as difficulty concentrating, feelings of worthlessness or excessive or inappropriate guilt, hopelessness, recurrent thoughts of death or suicide, changes in appetite or sleep, psychomotor agitation or retardation, and reduced energy or fatigue. There have never been any prior manic, hypomanic, or mixed episodes, which would indicate the presence of a Bipolar disorder. Inclusions:                Seasonal depressive disorder Exclusions:    ...
Post a Comment
Read more