A clear liquid fatty acid at room temperature. Valproate is believed to affect the
function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human
brain, making it an alternative to lithium salts in treatment of bipolar disorder.
In addition to blocking transamination of GABA, Valproate is believed to reverse
the transamination process to form more GABA. Hence, Valproate indirectly acts as
a GABA agonist. However, several other mechanisms of action in neuropsychiatric disorders
have been proposed for valproic acid in recent years.
Valproic acid also blocks the voltage-gated sodium channels and T-type Calcium channels.
These mechanisms make Valproic Acid a Broad Spectrum Anticonvulsant drug.
It has found clinical use as:
An anticonvulsant and mood-stabilising drug, primarily in the treatment of epilepsy,
bipolar disorder, and, less commonly, major depression.
To treat migraine headaches.
To treat schizophrenia.
Related drugs include the sodium salts sodium valproate, used as an anticonvulsant,
and a combined formulation, valproate semisodium, used as a mood stabilizer and additionally
in the U.S. as an anticonvulsant.
Wadzinski J, Franks R, Roane D, Bayard M (2007). "Valproate-associated Hyperammonemic
Encephalopathy". The Journal of the American Board of Family Medicine 20 (5): 499.
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Williams DC Jr, Massey GV, Russell EC, Riley RS, Ben-Ezra J. (2007). "Translocation
positive acute myeloid leukemia associated with valproic acid therapy". Pediatric
Blood and Cancer. Mar 29 (3): 641–3.
Coyle TE, Bair AK, Stein C, Vajpayee N, Mehdi S, Wright J. (2005). "Acute leukemia
associated with valproic acid treatment: a novel mechanism for leukemogenesis?".
Pediatric Blood and Cancer Apr (78): 256–60.
Ricard C, Martin K, Tournier M, Bégaud B, Verdoux H (2005). "[A case of Parkinsonian
syndrome, cognitive impairment and hyperammonemia induced by divalproate sodium prescribed
for bipolar disorder]" (in French). L'Encéphale 31 (1 Pt 1): 98–101. Science Direct
Side effects may occur such as:
Weight gain.
Dyspepsia
Fatigue.
Peripheral oedema.
Acne, dizziness.
Drowsiness.
Hair loss.
Headaches.
Nausea.
Sedation.
Tremor.
Serious Side effects may occur such as:
Preexisting severe hepatic (liver) and/or renal (kidney) damage and certain cases
of metastatic cancer.
Severe hepatitis or pancreatitis.
Marked bone marrow depression.
Urea cycle disorders, and coagulation hematological disorders.
Hyperammonemia, which can lead to brain damage. Valproate levels within the normal
range are capable of causing hyperammonemia and ensuing encephalopathy. There have
been reports of brain encephalopathy developing without hyperammonemia or elevated
valproate levels.
Acute hematological toxicities, especially in children, including rare reports of
myelodysplasia and acute leukemia-like syndrome.
Cognitive dysfunction.
Parkinsonian symptoms.
Pseudoatrophic brain changes in long-term treatment with valproic acid.
