What are the side effects of valproic acid?

From the Guidelines

Valproic acid can cause several serious side effects, including liver damage, pancreatitis, and blood disorders, and its use has been associated with complications such as thrombocytopenia and hepatotoxicity 1. The most common side effects of valproic acid include:

• Nausea and vomiting
• Stomach pain
• Drowsiness
• Dizziness
• Tremors
• Weight gain More serious side effects may include:
• Liver damage, which can present as yellowing of the skin or eyes, dark urine, or unusual tiredness
• Pancreatitis, which can cause severe abdominal pain, nausea, and vomiting
• Blood disorders, such as decreased platelets (thrombocytopenia) or white blood cells
• Neurological effects, including confusion, hallucinations, or unusual thoughts
• Birth defects if taken during pregnancy
• Decreased bone density with long-term use According to a study published in 2021, the use of valproic acid has been associated with complications such as thrombocytopenia and hepatotoxicity 1. Another study published in 2002 found that valproic acid can cause endocrine disorders, including polycystic ovaries and hyperandrogenism, particularly in women with epilepsy 1. It is essential for patients taking valproic acid to report any unusual symptoms to their healthcare provider immediately, especially signs of liver problems, unusual bleeding or bruising, or severe neurological symptoms. Regular blood tests are typically required to monitor liver function and blood counts while taking this medication.

From the FDA Drug Label

Dermatologic: Transient hair loss, skin rash, photosensitivity, generalized pruritus, erythema multiforme, and Stevens-Johnson syndrome. Rare cases of toxic epidermal necrolysis have been reported including a fatal case in a 6 month old infant taking valproate and several other concomitant medications An additional case of toxic epidermal necrosis resulting in death was reported in a 35 year old patient with AIDS taking several concomitant medications and with a history of multiple cutaneous drug reactions. Psychiatric: Emotional upset, depression, psychosis, aggression, hyperactivity, hostility, and behavioral deterioration. Musculoskeletal: Weakness. Hematologic: Thrombocytopenia and inhibition of the secondary phase of platelet aggregation may be reflected in altered bleeding time, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage Hepatic: Minor elevations of transaminases (e.g., SGOT and SGPT) and LDH are frequent and appear to be dose-related. Endocrine: Irregular menses, secondary amenorrhea, breast enlargement, galactorrhea, and parotid gland swelling Pancreatic: Acute pancreatitis, including fatalities Metabolic: Hyperammonemia, hyponatremia, and inappropriate ADH secretion Genitourinary: Enuresis and urinary tract infection Special Senses: Hearing loss, either reversible or irreversible, has been reported; however, a cause and effect relationship has not been established. Other: Allergic reaction, anaphylaxis, edema of the extremities, lupus erythematosus, bone pain, cough increased, pneumonia, otitis media, bradycardia, cutaneous vasculitis, fever, and hypothermia

The side effects of valproic acid include:

• Dermatologic reactions: transient hair loss, skin rash, photosensitivity, generalized pruritus, erythema multiforme, and Stevens-Johnson syndrome
• Psychiatric problems: emotional upset, depression, psychosis, aggression, hyperactivity, hostility, and behavioral deterioration
• Musculoskeletal issues: weakness
• Hematologic effects: thrombocytopenia, altered bleeding time, petechiae, bruising, hematoma formation, epistaxis, and frank hemorrhage
• Hepatic effects: minor elevations of transaminases, LDH
• Endocrine effects: irregular menses, secondary amenorrhea, breast enlargement, galactorrhea, and parotid gland swelling
• Pancreatic effects: acute pancreatitis
• Metabolic effects: hyperammonemia, hyponatremia, and inappropriate ADH secretion
• Genitourinary effects: enuresis and urinary tract infection
• Special senses effects: hearing loss
• Other effects: allergic reaction, anaphylaxis, edema of the extremities, lupus erythematosus, bone pain, cough increased, pneumonia, otitis media, bradycardia, cutaneous vasculitis, fever, and hypothermia 2 The common side effects of valproic acid 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 2

From the Research

Valproic Acid Side Effects

The side effects of valproic acid are numerous and can be categorized into several groups. Some of the common side effects include:

• Nausea and vomiting
• Weight gain
• Hair loss
• Tremor
• Changes in behavior
• Slowed thinking
• Impaired liver function 3

Hepatotoxicity and Pancreatitis

Valproic acid has been associated with hepatotoxicity, which can range from reversible hepatic dysfunction to irreversible hepatic failure 4. Additionally, there have been cases of fatal acute pancreatitis caused by valproic acid, often due to delayed diagnosis or unsuspected diagnosis 5.

Blood-Related Side Effects

Valproic acid can also cause blood-related side effects, such as:

• Thrombocytopenia (low platelet count) 6
• Pancytopenia (low blood cell count) 3
• Panhypogammaglobulinemia (low levels of immunoglobulins) 3
• Blood dyscrasias (blood disorders) 3

Neurological and Metabolic Side Effects

Other side effects of valproic acid include:

• Neurological toxicity 7
• Metabolic and endocrine adverse events 7
• Hyperammonemic encephalopathy (elevated ammonia levels in the blood) 7
• Mitochondrial toxicity 7
• Teratogenicity (birth defects) 7