Sodium Valproate: A Comprehensive Guide

Sodium valproate is a widely prescribed antiepileptic medication that plays a crucial role in managing various neurological and psychiatric disorders. First introduced in the 1960s, sodium valproate has become a cornerstone in the treatment of epilepsy and bipolar affective disorder. It is derived from valproic acid and works by stabilising electrical signals in the brain, thus preventing seizures and mood swings. Available under brand names such as Epilim and Depakote, sodium valproate is recognised by the World Health Organization as an essential medicine due to its broad efficacy and safety when used appropriately.

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Uses of Sodium Valproate

Sodium valproate is most commonly used in managing generalised epilepsy, including absence, tonic-clonic, and myoclonic seizures. It is also effective in treating bipolar disorder, especially in managing acute manic episodes. Additionally, sodium valproate is used for migraine prophylaxis and occasionally prescribed off-label for conditions like schizoaffective disorder, borderline personality disorder, and neuropathic pain. Its wide-ranging effects on the central nervous system make sodium valproate a versatile medication in both neurology and psychiatry. It is also considered a second-line option for agitation in dementia and some mood disorders resistant to standard therapies.

Dosage and Administration

Sodium valproate dosages vary depending on the condition and patient characteristics such as age, weight, and organ function. For epilepsy, adults typically begin with 600 mg/day in divided doses, which may be increased by 200 mg every three days, up to a maximum of 2,000–2,500 mg/day. In children, doses are calculated by weight (20–30 mg/kg/day), titrated slowly to avoid adverse effects. For bipolar disorder, a common starting dose is 750 mg/day, with gradual adjustments based on clinical response and plasma concentration. Sodium valproate is best taken with food to reduce gastrointestinal discomfort. It is available in oral (tablets, syrup) and intravenous forms. Plasma drug levels should be monitored to ensure therapeutic efficacy and avoid toxicity, especially when polytherapy is employed.

Dose Adjustment in Different Conditions

Renal Impairment: Sodium valproate is predominantly metabolised by the liver, so mild to moderate renal impairment usually does not necessitate dose changes. However, in cases of severe renal failure, accumulation of active metabolites may occur. Cautious dose adjustment and frequent plasma level monitoring are advised.
Hepatic Impairment: Sodium valproate is contraindicated in patients with significant hepatic dysfunction, particularly those with a history of liver disease. Liver function tests (ALT, AST, bilirubin) must be conducted regularly, especially during the first six months. Children under two are at higher risk of hepatotoxicity.
Pregnancy: Sodium valproate is known to be teratogenic. Its use during pregnancy is linked with neural tube defects (e.g., spina bifida), congenital malformations, facial dysmorphism, and developmental disorders. It should only be prescribed when no safer alternatives are available. In 2025, regulatory guidelines demand a thorough risk-benefit evaluation, signed consent, and effective contraception for all women of childbearing age on sodium valproate.

Effects and Side Effects

Sodium valproate is generally well tolerated but may cause a wide spectrum of side effects, varying in severity from mild to potentially life-threatening. Common side effects include gastrointestinal upset (nausea, vomiting, diarrhoea), tremor, increased appetite, weight gain, hair thinning, and drowsiness. Mood changes, sedation, and coordination problems may also occur. More serious adverse effects include hepatotoxicity, pancreatitis, encephalopathy (due to hyperammonaemia), thrombocytopenia, menstrual irregularities, and polycystic ovary syndrome (PCOS). Regular monitoring of liver enzymes, ammonia levels, coagulation profile, and complete blood counts is essential throughout treatment.

How Sodium Valproate Works

Sodium valproate enhances the availability of gamma-aminobutyric acid (GABA), the brain’s primary inhibitory neurotransmitter, which reduces excessive neuronal firing and excitability. It also inhibits voltage-gated sodium channels and T-type calcium channels, stabilising neural membranes and preventing seizure propagation. These multimodal mechanisms help to suppress seizure activity and exert mood-stabilising effects in patients with bipolar disorder and other psychiatric conditions.

Drug Combinations and Considerations During Infusion

Sodium valproate is frequently combined with other antiepileptic drugs such as lamotrigine, levetiracetam, or benzodiazepines like clonazepam. Interactions are common and can lead to increased toxicity or reduced therapeutic efficacy. For instance, valproate increases lamotrigine levels, raising the risk of serious rashes including Stevens-Johnson syndrome. When administered intravenously, sodium valproate must be diluted in 0.9% saline or 5% dextrose and infused slowly over at least 60 minutes. Infusion-related complications such as hypotension, bradycardia, and thrombophlebitis must be monitored closely. Dose adjustments may be necessary based on infusion tolerance and clinical response.

Presentation and Form of Sodium Valproate

Form	Strength	Route	Common Brand
Tablets	200 mg, 500 mg	Oral	Epilim
Syrup	200 mg/5 mL	Oral	Epilim Syrup
Injection	400 mg/4 mL	IV	Depakote IV
Gastro-resistant tabs	300 mg, 500 mg	Oral	Epilim Chrono
Modified-release tabs	300 mg, 500 mg	Oral	Epilim Chronosphere

Pharmacokinetics and Pharmacodynamics

Absorption: Rapid and complete absorption after oral administration; peak plasma levels are achieved within 1–4 hours.
Distribution: Extensively protein-bound (90–95%), volume of distribution varies with age and health status.
Metabolism: Undergoes hepatic metabolism via glucuronidation and mitochondrial beta-oxidation.
Excretion: Less than 5% excreted unchanged in urine; mainly excreted as metabolites.
Half-life: Ranges between 9 to 16 hours depending on age, liver function, and concomitant medications.
Mechanism of Action: Enhances GABA activity, inhibits sodium and calcium channel-mediated neuronal activity.
Bacterial Coverage: Sodium valproate has no antibacterial activity and should not be used to treat infections.

Drug Interactions

Sodium valproate has significant interactions with many drugs:

Increased effects/toxicity: Lamotrigine (risk of severe rash), phenobarbital (CNS depression), warfarin (enhanced anticoagulation), clozapine (increased sedation).
Reduced efficacy: Carbamazepine and phenytoin may lower valproate levels; enzyme inducers like rifampin can reduce its effectiveness.
Alcohol: Potentiates CNS depressive effects and increases risk of sedation, dizziness, and liver damage. Strict avoidance is advised.

Comparison with Other Antiepileptics

Drug	Main Use	Sedation	Pregnancy Risk	Liver Safety
Sodium Valproate	Generalised epilepsy, bipolar disorder	Moderate	High (Category D)	Hepatotoxic potential
Carbamazepine	Focal seizures, trigeminal neuralgia	Moderate	Medium	Hepatotoxic potential
Lamotrigine	Epilepsy, bipolar depression	Low	Lower risk	Safer in liver disease
Levetiracetam	Broad-spectrum epilepsy	Low	Category B	Minimal liver metabolism
Topiramate	Epilepsy, migraine prevention	Moderate	Medium	Weight loss risk

Precautions and Special Considerations

Routine monitoring of liver function, full blood count, and serum ammonia is essential when using sodium valproate. Extra caution is needed in elderly patients, those with pre-existing liver dysfunction, and children under two years of age. Because of its high teratogenic potential, sodium valproate must be prescribed with a strict pregnancy prevention programme. The drug should never be stopped abruptly, as this may trigger rebound seizures or manic relapse. Patients should be counselled on adherence, side effects, and the importance of regular follow-up.

Toxicity or Overdose and Antidote

Overdose symptoms include deep coma, respiratory depression, hypotension, hypothermia, metabolic acidosis, and possible brain oedema. Supportive treatment is the mainstay. Prompt administration of activated charcoal (within 1–2 hours of ingestion) can reduce absorption. Haemodialysis is effective for severe cases to remove sodium valproate from the system. Carnitine supplementation may be considered in valproate-induced hepatotoxicity or hyperammonaemia.

Recent Updates in 2025 and Guidelines

In 2025, the MHRA (Medicines and Healthcare products Regulatory Agency) updated its regulations surrounding sodium valproate. Prescribers are now required to complete a Risk Acknowledgement Form annually for women of childbearing potential. Patients must undergo regular specialist reviews to reassess the risk-benefit ratio. Efforts are ongoing to develop safer analogues and enhanced formulations (such as extended-release preparations) to reduce the frequency of dosing and improve patient compliance. Public awareness campaigns and better labelling have also been mandated to ensure informed patient choices.

Facts to Remember

Sodium valproate is a broad-spectrum antiepileptic and mood stabiliser.
It has a high teratogenic risk; avoid in pregnancy unless no alternative exists.
Regular monitoring of liver enzymes, blood counts, and drug levels is necessary.
Sodium valproate increases GABA levels and inhibits overactive neurons.
Alcohol and abrupt discontinuation must be strictly avoided.
Patient education and contraception are essential in women of reproductive age.

Did You Know?

Sodium valproate was originally used as a solvent during experimental drug testing. In 1962, researchers discovered its unexpected anticonvulsant properties when it prevented seizures in animal models. This serendipitous finding revolutionised epilepsy treatment and has since helped millions of patients worldwide lead better, more stable lives.