A review of valproate in psychiatric practice

Abstract

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.

HDAC1 links early life stress to schizophrenia-like phenotypes

“…In fact, valproate given in combination with atypical antipsychotics shows beneficial effects in preclinical (18) and clinical (19) studies. These data have to be interpreted with care, however, because besides its action on HDACs, valproate affects many other cellular processes (20). Postmortem analysis of human brain tissue suggested that Hdac1 levels are elevated in the prefrontal cortex and hippocampus of patients with schizophrenia (21,22).…”

HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells

“…32 Recently, VPA was rediscovered as an HDAC inhibitor and has been tested in clinical trials for hematologic malignancies such as myelodysplastic syndrome and acute myeloblastic leukemia. 33,34 Unfortunately, VPA as a single agent is not so efficacious and so its combination with other drugs is under consideration.…”

“…VPA-induced cell death required 2-5 mM, which apparently exceed the in vivo toxic concentrations, according to cumulative clinical data. 32,35 This at least partly explains why VPA failed to show considerable effects as a single agent in clinical trials. We then examined whether another HDAC inhibitor romidepsin (formerly FK228 or depsipeptide) had the same effect.…”

Comparison of Serum Valproic Acid Determination Through Gas and High Performance Liquid Chromatography Methods

“…It is less commonly used in the treatment of major depression (1,2). Valproic acid acts on dopamine and glutamine neurotransmission as well as intracellular signaling (3). Valproic acid is marketed under various pharmaceutical preparations and forms.…”