What are the major side effects of sodium valproate (Valproic Acid)?

From the Guidelines

Sodium valproate is associated with significant side effects, including weight gain, menstrual irregularities, polycystic ovary syndrome, and hyperandrogenism, as well as more severe adverse effects like liver toxicity and pancreatitis. The major side effects of sodium valproate can be categorized into several groups, including:

• Gastrointestinal disturbances, such as nausea, vomiting, and diarrhea
• Weight gain, which can lead to insulin resistance and increase the risk of polycystic ovary syndrome (PCOS) in women 1
• Menstrual irregularities, including amenorrhoea, oligomenorrhoea, and irregular menstruation, which are reported in up to 45% of women taking valproate monotherapy 1
• Hyperandrogenism, characterized by elevated testosterone levels and hirsutism, which is observed in up to 30% of women taking valproate monotherapy 1
• Polycystic ovary syndrome (PCOS), which is diagnosed in up to 64% of women taking valproate monotherapy 1
• More severe adverse effects, such as liver toxicity (hepatotoxicity) and pancreatitis, which can be life-threatening 1
• Blood disorders, including thrombocytopenia (low platelets) and leukopenia (low white blood cells), which may occur during treatment with valproate 1
• Neurological effects, including drowsiness, confusion, and ataxia (lack of muscle coordination), which can impact quality of life
• Teratogenic effects, including neural tube defects, facial abnormalities, and developmental delays, which make valproate contraindicated in pregnant women or women of childbearing age without effective contraception. Regular monitoring of liver function, complete blood count, and drug levels is necessary during treatment to detect adverse effects early and minimize the risk of morbidity and mortality.

From the FDA Drug Label

The common side effects of Valproic Acid Oral Solution, USP include: •nausea •headache •sleepiness •vomiting •weakness •tremor •dizziness •stomach pain •blurry vision •double vision •diarrhea •increased appetite •weight gain •hair loss •loss of appetite •problems with walking or coordination

Valproic Acid Oral Solution, USP can cause other serious side effects including: •Bleeding problems: red or purple spots on your skin, bruising, pain and swelling into your joints due to bleeding or bleeding from your mouth or nose. •High ammonia levels in your blood: feeling tired, vomiting, changes in mental status. •Low body temperature (hypothermia): drop in your body temperature to less than 95°F, feeling tired, confusion, coma. •Allergic (hypersensitivity) reactions: fever, skin rash, hives, sores in your mouth, skin blistering and peeling of your skin, swelling of your lymph nodes, swelling of your face, eyes, lips, tongue, or throat, trouble swallowing or breathing.

The major side effects of sodium valproate include:

• Gastrointestinal issues: nausea, vomiting, diarrhea, stomach pain, and changes in appetite
• Nervous system problems: sleepiness, weakness, tremor, dizziness, blurry vision, double vision, and problems with walking or coordination
• Bleeding problems: red or purple spots on the skin, bruising, and bleeding from the mouth or nose
• Metabolic issues: high ammonia levels in the blood, low body temperature, and weight changes
• Allergic reactions: fever, skin rash, hives, and swelling of the face, eyes, lips, tongue, or throat
• Other issues: hair loss, loss of appetite, and changes in mental status 2, 2, 2

From the Research

Major Side Effects of Sodium Valproate

The major side effects of sodium valproate include:

• Hepatotoxicity, which can be fatal in some cases 3, 4, 5, 6, 7
• Pancreatitis, which can also be fatal 3, 5, 6
• Teratogenicity, which can cause birth defects in children born to mothers taking the drug 3, 6
• Skin lesions, which have been observed in some patients taking high doses of the drug 4
• Weight gain, which has been reported in some adult women taking the drug 5
• Increased amylase values, which can indicate pancreatitis 5
• Eosinophilia, which can be a sign of an allergic reaction 5
• Increased gamma-glutamyltranspeptidase, which can indicate liver damage 5

Specific Studies

• A study published in 2001 found that pancreatitis was a rare but potentially fatal side effect of sodium valproate 3
• A study published in 2018 found that high doses of sodium valproate can cause hepatotoxicity and skin lesions in adult albino rats 4
• A study published in 1986 found that 71.6% of patients taking sodium valproate developed side effects, including increased amylase values, eosinophilia, and weight gain 5
• A review published in 2022 found that the risk of hepatotoxicity and pancreatitis is much lower in the general population than in patients with certain risk factors 6
• A study published in 1988 found that valproate-associated hepatotoxicity is a rare but potentially fatal side effect of the drug, and that unsaturated metabolites of valproate may contribute to the hepatotoxicity 7