Cited by 404Bipolar Disorder and TreatmentTreatment of Major DepressionNeuroscience and Neuropharmacology Research

Therapeutic potential of mood stabilizers lithium and valproic acid:Beyond bipolar disorder

Open access
Chiu, Chi-Tso, Wang, Zhifei, Hunsberger, Joshua G., Chuang, De-Maw·2013·Pharmacological Reviews

Abstract

The mood stabilizers lithium and valproic acid (VPA) are traditionally used to treat bipolar disorder (BD), a severe mental illness arising from complex interactions between genes and environment that drive deficits in cellular plasticity and resiliency. The therapeutic potential of these drugs in other central nervous system diseases is also gaining support. This article reviews the various mechanisms of action of lithium and VPA gleaned from cellular and animal models of neurologic, neurodegenerative, and neuropsychiatric disorders. Clinical evidence is included when available to provide a comprehensive perspective of the field and to acknowledge some of the limitations of these treatments. First, the review describes how action at these drugs' primary targets--glycogen synthase kinase-3 for lithium and histone deacetylases for VPA--induces the transcription and expression of neurotrophic, angiogenic, and neuroprotective proteins. Cell survival signaling cascades, oxidative stress pathways, and protein quality control mechanisms may further underlie lithium and VPA's beneficial actions. The ability of cotreatment to augment neuroprotection and enhance stem cell homing and migration is also discussed, as are microRNAs as new therapeutic targets. Finally, preclinical findings have shown that the neuroprotective benefits of these agents facilitate anti-inflammation, angiogenesis, neurogenesis, blood-brain barrier integrity, and disease-specific neuroprotection. These mechanisms can be compared with dysregulated disease mechanisms to suggest core cellular and molecular disturbances identifiable by specific risk biomarkers. Future clinical endeavors are warranted to determine the therapeutic potential of lithium and VPA across the spectrum of central nervous system diseases, with particular emphasis on a personalized medicine approach toward treating these disorders.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1124/pr.111.005512

Cites

580 of 580 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Chiu, C.-T., Wang, Z., Hunsberger, J. G., & Chuang, D.-M.
Affiliations
National Institutes of Health (US)
Venue
Pharmacological Reviews
Publisher
Elsevier BV
Published
2013-01
Volume
65
Issue
1
Pages
105-142
ISSN
0031-6997 (ISSN-L)
OpenAlex
W2098378665
Cited by
404
References
580
Citations by year
2026: 19 · 2025: 20 · 2024: 14 · 2023: 20 · 2022: 19 · 2021: 39 · 2020: 31 · 2019: 29 · 2018: 27 · 2017: 33 · 2016: 53 · 2015: 42 · 2014: 45 · 2013: 13
FWCI
6.95
Type
journal article
Language
en
Open access
Locations
  • Pharmacological Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health and Human Services
  • National Institutes of Health
  • National Institute of Mental Health
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
lithium, valproic acid, mood stabilizers, bipolar disorder, glycogen synthase kinase-3, histone deacetylase, neuroprotection, neurotrophic factors, angiogenesis, oxidative stress, protein quality control, stem cell homing, microRNA, neuroinflammation, blood-brain barrier, neurogenesis, anti-inflammation, personalized medicine, risk biomarkers, neurodegenerative diseases, neuropsychiatric disorders
MeSH terms
Animals, Bipolar Disorder, Central Nervous System Diseases, Humans, Valproic Acid, Lithium Compounds, Antimanic Agents, Neuroprotective Agents

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review