Valproate for schizophrenia

Schwarz, Christian; Volz, Anja; Li, Chunbo; Leucht, Stefan

doi:10.1002/14651858.cd004028.pub3

Cited by 57 publications

(50 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More recent clinical studies report results that are mixed and show little benefit of adjunctive VPA administration in SZ (Casey et al, 2009;Larrison et al, 2011). A review of the literature suggests that VPA can be effective in treating some forms of SZ and aggression, ie, SZ with comorbid mood disorder (schizoaffective disorder) and treatment-resistant patients (Schwarz et al, 2010). A comprehensive clinical trial involving large numbers of psychiatric admissions determined that the efficacy of VPA depends on whether the extended release formulation (divalproex) or generic VPA is initially administered (Wassef et al, 2005).…”

Section: Antipsychotic Drugs Reduce Promoter Methylationmentioning

confidence: 99%

The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders

Grayson

Guidotti

2012

Neuropsychopharmacol

244

214

View full text Add to dashboard Cite

Major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP) with psychosis (BP+ ) express a complex symptomatology characterized by positive symptoms, negative symptoms, and cognitive impairment. Postmortem studies of human SZ and BP+ brains show considerable alterations in the transcriptome of a variety of cortical structures, including multiple mRNAs that are downregulated in both inhibitory GABAergic and excitatory pyramidal neurons compared with non-psychiatric subjects (NPS). Several reports show increased expression of DNA methyltransferases in telencephalic GABAergic neurons. Accumulating evidence suggests a critical role for altered DNA methylation processes in the pathogenesis of SZ and related psychiatric disorders. The establishment and maintenance of CpG site methylation is essential during central nervous system differentiation and this methylation has been implicated in synaptic plasticity, learning, and memory. Atypical hypermethylation of candidate gene promoters expressed in GABAergic neurons is associated with transcriptional downregulation of the corresponding mRNAs, including glutamic acid decarboxylase 67 (GAD67) and reelin (RELN). Recent reports indicate that the methylation status of promoter proximal CpG dinucleotides is in a dynamic balance between DNA methylation and DNA hydroxymethylation. Hydroxymethylation and subsequent DNA demethylation is more complex and involves additional proteins downstream of 5-hydroxymethylcytosine, including members of the base excision repair (BER) pathway. Recent advances in our understanding of altered CpG methylation, hydroxymethylation, and active DNA demethylation provide a framework for the identification of new targets, which may be exploited for the pharmacological intervention of the psychosis associated with SZ and possibly BP+ .

show abstract

Section: Antipsychotic Drugs Reduce Promoter Methylationmentioning

confidence: 99%

The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders

Grayson

Guidotti

2012

Neuropsychopharmacol

244

214

View full text Add to dashboard Cite

show abstract

“…A Cochrane review that assessed the effectiveness of valproate as an adjunct to antipsychotic therapy in schizophrenia found that valproate, in comparison to placebo, led to no significant benefit on clinical global impression or the general mental state at the end point [54]. Those in the valproate group experienced sedation more frequently than those in the placebo group.…”

Section: Adjunctive Treatment In Schizophreniamentioning

confidence: 99%

A review of valproate in psychiatric practice

Haddad

Das

Ashfaq

et al. 2009

Expert Opinion on Drug Metabolism & Toxicology

122

View full text Add to dashboard Cite

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.

show abstract

“…Augmentation strategies that target schizophrenic symptoms include antidepressants; e.g., tricyclic antidepressants (TCAs) (Siris, 1993), selective serotonin reuptake inhibitor (SSRI, Sepehry et al, 2007), trazodone (Decina et al, 1994;Hayashi et al, 1997), mianserin (Grinshpoon et al, 2000;Shiloh et al, 2002), and nefazodone (Joffe et al, 1999). Other augmentation strategies include carbamazepine (Leucht et al, 2007a), valproate (Schwarz et al, 2008), lamotrigine , lithium (Leucht et al, 2007b), sex hormones (Ko et al, 2008), COX-inhibitors (Riedel et al, 2005), glutamatergic drugs (Tuominen et al, 2006), and acetylcholine esterase inhibitors (Keefe et al, 2008). Their outcomes differ widely in terms of efficacy and human psychopharmacology Hum.…”

Section: Introductionmentioning

confidence: 99%