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Valproic acid, valproate and divalproex in the maintenance treatment of bipolar disorder

2001· review· en· 260 citations· W4231774701 on OpenAlex· 10.1002/14651858.cd003196

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian affiliationAn author listed a Canadian institution. This is the only route the usual frame has.

Full frame distilled prediction

Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

Candidate categories
Meta-epidemiology (narrow), Meta-epidemiology (broad), Insufficient payload (model declined to judge)
Consensus categories
Meta-epidemiology (narrow)
Domain
Candidate signal: noneConsensus signal: none
Study design
Candidate signal: Systematic reviewConsensus signal: Systematic review
Genre
Candidate signal: ReviewConsensus signal: Review
Teacher disagreement score
0.398
Threshold uncertainty score
1.000
Validation status
machine_predicted_unvalidated · codex-gemma-dda1882f352a

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0110.003
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0180.002
Bibliometrics0.0010.003
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0020.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.001

Machine scores (provisional)

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Opus teacher head0.134
GPT teacher head0.382
Teacher spread
0.248 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

BACKGROUND: Although lithium has been the most commonly used maintenance treatment in bipolar disorder for several decades, valproate is being used increasingly - especially in the United States of America. There is a need to clarify whether the increasingly prominent prophylactic role of valproate in bipolar disorder is justified. OBJECTIVES: To review the effectiveness of valproate, relative to placebo, other mood stabilisers and antipsychotics, in the prevention and/or attenuation of acute episodes of bipolar disorder. The effectiveness of valproate was considered in terms of mood symptoms, mortality, general health, social functioning, adverse effects and overall acceptability to patients. SEARCH STRATEGY: The CCDAN group search strategy was used. The following databases were searched: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), The Cochrane Controlled Clinical Trials Register (CCCTR), EMBASE, MEDLINE, LILACS, PsycLIT and Psyndex. Reference lists of relevant papers and major textbooks of mood disorder were examined. Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials which compared valproate with placebo, alternative mood stabilisers (including lithium and carbamazepine) or neuroleptics, where the stated intent of intervention was the maintenance treatment of bipolar disorder. Participants were males and females of all ages with a diagnosis of bipolar disorder however diagnosed, approximating to ICD 10 Code F31 and DSM IV 296, but including patients diagnosed as ICD-9 manic depressive psychosis and DSM-III and DSM-IIIR bipolar disorder. DATA COLLECTION AND ANALYSIS: Data were extracted from the original reports individually by two reviewers. The main outcomes to be assessed were: 1. The effectiveness of valproate treatment in preventing or attenuating further episodes of bipolar disorder, including its effectiveness in rapid cycling disorder. 2. The acceptability of valproate treatment to patients. 3. The prevalence of side-effects. 4. Mortality on valproate treatment. Outcomes concerning relapse/recurrence were analysed excluding data from discontinuation studies, which were to be analysed separately. Sub-group analyses were to be performed to examine the effects of valproate treatment in rapid cycling bipolar disorder and previous mood stabiliser non-responders. Data were analysed using Review Manager version 4.1. MAIN RESULTS: One trial of 12 months duration with 372 participants was identified comparing lithium, divalproex and placebo. It had several methodological limitations. The primary analysis of time to occurrence of mood episode described in the main trial report found no reliable difference between the treatments, although there was a trend for divalproex to be more effective than lithium. In the analysis in this review, patients taking divalproex who left the study because of the occurrence of an mood episode were significantly less in number than those on placebo (RRR 37%; RR 0.63; 95% CI 0.44 to 0.90). There was no significant difference in the numbers of patients in receipt of divalproex compared with those in receipt of lithium who left the study because they suffered any mood episode. (RRR 22%; RR 0.78; 95% C.I. 0.52 to 1.17). There was insufficient information to allow sub-group analyses of rapid-cycling disorder. The divalproex group had significantly more patients suffering tremor (RRI 223%; RR 3.23; 95% C.I. 1.85 to 5.62), weight gain (RRI 187%; RR 2.87; 95% C.I. 1.34 to 6.17) and alopecia (RRI 143%; RR 2.43; 95% C.I. 1.05 to 5.65) than the placebo group. In comparison with the lithium, divalproex was associated with more frequent sedation (RRI 58%; RR 1.58; 95% C.I. 1.08 to 2.32) and infection (RRI 107%; RR 2.07; 95% C.I. 1.16 to 3.68), but less suffered thirst (RRR 62%; RR 0.38; 95% C.I. 0.18 to 0.81) and polyuria (RRR 57%; RR 0.43; 95% C.I. 0.22 to 0.82). REVIEWER'S CONCLUSIONS: In view of the equivocal findings of this review, conclusions about the efficacy and acceptability of valproate compared to placebo and lithium cannot be made with any degree of confidence. With current evidence, patients and clinicians would probably wish to use lithium before valproate for maintenance treatment. At present, the observed shift of prescribing practice to valproate is not based on reliable evidence of efficacy

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
Cochrane Database of Systematic Reviews
Topic
Field
Canadian institutions
University of British Columbia
Funders
not available
Keywords
Bipolar disorderPsychiatryMoodDivalproexMedicineLithium (medication)CarbamazepinePlaceboRandomized controlled trialLamotrigineBipolar I disorderPediatricsManiaEpilepsyInternal medicine
Has abstract in OpenAlex
yes