Valproate (depakine-chrono) in the acute treatment of outpatients with generalized anxiety disorder without psychiatric comorbidity: Randomized, double-blind placebo-controlled study

Aliyev, Nadir A.; Aliyev, Zafar N.

doi:10.1016/j.eurpsy.2007.08.001

Cited by 52 publications

(25 citation statements)

References 33 publications

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“…Anecdotally, valproate has been reported to reduce agression related to acquired brain injury [66,67] but there are no RCTs to either support or refute this [68]. Beneficial effects of valproate have been reported in conduct disorder [69], generalized anxiety disorder [70] and the management of alcohol withdrawal symptoms [71,72].…”

Section: Miscellaneous Conditionsmentioning

confidence: 94%

A review of valproate in psychiatric practice

Haddad

Das

Ashfaq

et al. 2009

Expert Opinion on Drug Metabolism & Toxicology

122

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Valproate (2-propylpentanoate) is available as valproic acid, sodium valproate and semisodium valproate. It has actions on dopamine, GABA and glutamate neurotransmission and intracellular signaling. Its main psychiatric use is to treat bipolar disorder. It has been used in other psychiatric disorders, including schizophrenia and borderline personality disorder, but data are insufficient to recommend this. In acute mania, valproate monotherapy has similar efficacy to antipsychotic drugs and lithium whereas the combination of valproate and an antipsychotic is more effective than either drug alone. In maintenance treatment of bipolar disorder, valproate monotherapy has comparable efficacy to olanzapine although placebo-controlled evidence is limited. Maintenance treatment with valproate and quetiapine or olanzapine is more efficacious than valproate alone when an acute episode responds to the combination. Common adverse effects of valproate include weight gain, gastrointestinal symptoms, sedation, tremor and mild elevation of hepatic enzymes. Serious hepatic toxicity is rare in adults. Many adverse effects are dose related and resolve with dose reduction. Valproate is teratogenic and specifically associated with neural tube defect. Preliminary evidence has linked in utero exposure to decreased verbal intelligence in the offspring. These effects, plus a probable increased risk of polycystic ovary syndrome, limit valproate's use in women of childbearing potential.

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Section: Miscellaneous Conditionsmentioning

confidence: 94%

A review of valproate in psychiatric practice

Haddad

Das

Ashfaq

et al. 2009

Expert Opinion on Drug Metabolism & Toxicology

122

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“…Randomized controlled trials have shown that anticonvulsants (valproate, pregabalin) are effective anxiolytics in GAD patients (Aliyev & Aliyev, 2008;Mula, Pini, & Cassano, 2007). To our knowledge, they have not yet been tested in the CC model, but a cued fear conditioning study found that valproate enhances extinction, but also enhances renewal of the original conditioned fear, which makes it difficult to draw a straightforward conclusion about a potential anxiolytic effect (Bredy & Barad, 2008).…”

Section: Predictive Validitymentioning

confidence: 98%

Contextual conditioning in rats as an animal model for generalized anxiety disorder

Luyten

Vansteenwegen

Kuyck

et al. 2011

Cogn Affect Behav Neurosci

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Animal models of psychiatric disorders are important translational tools for exploring new treatment options and gaining more insight into the disease. Thus far, there is no systematically validated animal model for generalized anxiety disorder (GAD), a severely impairing and difficult-to-treat disease. In this review, we propose contextual conditioning (CC) as an animal model for GAD. We argue that this model has sufficient face validity (there are several symptom similarities), predictive validity (it responds to clinically effective treatments), and construct validity (the underlying mechanisms are comparable). Although the refinement and validation of an animal model is a never-ending process, we want to give a concise overview of the currently available evidence. We suggest that the CC model might be a valuable preclinical tool to enhance the development of new treatment strategies and our understanding of GAD.

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“…Of the 19 trials rejected at data selection, two presented duplicate data, 23 39 four presented insufficient data for extra ction, [44][45][46][47] and 13 presented insufficient network connections (that is, the only randomised controlled trials for a particular drug or the comparator in the study was inappropriate). [48][49][50][51][52][53][54][55][56][57][58][59][60] Table A on bmj.com gives details of the 27 included trials.…”

Section: Researchmentioning

confidence: 99%

Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis

Baldwin

Woods²,

Lawson³

et al. 2011

BMJ

262

145

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Objective To appraise the evidence for comparative efficacy and tolerability of drug treatments in patients with generalised anxiety disorder. Design Systematic review of randomised controlled trials. Primary Bayesian probabilistic mixed treatment metaanalyses allowed pharmacological treatments to be ranked for effectiveness for each outcome measure, given as percentage probability of being the most effective treatment. Secondary frequentist mixed treatment metaanalyses conducted with random effects model; effect size reported as odds ratio and 95% confidence interval. Data sources Medline, Embase, BIOSIS, PsycINFO, Health Economic Evaluations Database, National Health Service Economic Evaluation Database, and Database of Abstracts of Reviews of Effects via DataStar, and Cochrane Database of Systematic Reviews via Cochrane Library (January 1980 to February 2009). Eligibility criteria Double blind placebo controlled randomised controlled trials; published systematic reviews and meta-analyses of randomised controlled trials. Randomised controlled trials including adult participants (aged ≥18) receiving any pharmacological treatment for generalised anxiety disorder. Data abstraction methods Titles or abstracts reviewed initially, followed by review of full text publications for citations remaining after first pass. A three person team conducted screening; an independent reviewer checked a random selection (10%) of articles screened. Data extracted for meta-analysis were also independently reviewed. Main outcome measures Proportion of participants experiencing ≥50% reduction from baseline score on Hamilton anxiety scale (HAM-A) (response), proportion with final HAM-A score ≤7 (remission), proportion withdrawing from trial because of adverse events (tolerability). Results The review identified 3249 citations, and 46 randomised controlled trials met inclusion criteria; 27 trials contained sufficient or appropriate data for inclusion in the analysis. Analyses compared nine drugs (duloxetine, escitalopram, fluoxetine, lorazepam, paroxetine, pregabalin, sertraline, tiagabine, and venlafaxine). In the primary probabilistic mixed treatment meta-analyses, fluoxetine was ranked first for response and remission (probability of 62.9% and 60.6%, respectively) and sertraline was ranked first for tolerability (49.3%). In a subanalysis ranking treatments for generalised anxiety disorder currently licensed in the United Kingdom, duloxetine was ranked first for response (third across all treatments; 2.7%), escitalopram was ranked first for remission (second across all treatments; 26.7%), and pregabalin was ranked first for tolerability (second across all treatments; 7.7%). Conclusions Though the frequentist analysis was inconclusive because of a high level of uncertainty in effect sizes (based on the relatively small number of comparative trials), the probabilistic analysis, which did not rely on significant outcomes, showed that fluoxetine (in terms of response and remission) and sertraline (in terms of tolerability) seem t...

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Valproate (depakine-chrono) in the acute treatment of outpatients with generalized anxiety disorder without psychiatric comorbidity: Randomized, double-blind placebo-controlled study

Abstract: The authors believe this to be the first double-blind placebo-controlled randomization study to test the efficacy of a depakine-chrono in the management of anxiety disorders. They need to be replicated in a larger study group.

Cited by 52 publications

References 33 publications

A review of valproate in psychiatric practice

A review of valproate in psychiatric practice

Contextual conditioning in rats as an animal model for generalized anxiety disorder

Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis

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