Valproate (Depakote, Depakene)

Class

Anticonvulsant, mood stabilizer

Mechanism

Increases brain GABA levels by inhibiting GABA transaminase and enhancing GABA synthesis, modulates sodium and calcium channels, stabilizing neuronal membranes and mood

FDA-Approved Use

Epilepsy, bipolar disorder (acute mania), migraine prophylaxis

Off-Label Use

Status epilepticus, mixed and rapid-cycling bipolar disorder, catatonia (second-line), agitation and aggression in traumatic brain injury (TBI), agitation and aggression in neurodevelopmental disabilities, post-stroke aggression, agitation and psychosis in dementia

Formulation

Oral delayed-release and extended-release tablets/capsules, liquid formulation, intravenous formulation

Titration

250–500 mg p.o. nightly or twice daily, titrated based on serum levels and clinical response

Dose Range

Serum levels 50–125 mcg/mL (mood stabilization)

Kinetics

Hepatic metabolism via glucuronidation; half-life 9–16 hours; protein binding approximately 90%

Common AEs

Sedation, tremor, weight gain, nausea, alopecia, dizziness, gastrointestinal upset

Serious/Rare AEs

Hepatotoxicity, pancreatitis, thrombocytopenia, teratogenicity (neural tube defects)

Monitoring

Monitor valproate serum levels, complete blood count (CBC), liver function tests (LFTs), and weight every 3–6 months or sooner with dose changes

Black Box Warning

Hepatotoxicity, teratogenicity, pancreatitis

Considerations

Valproate is effective as a mood stabilizer in patients with seizure disorders but requires careful monitoring for drug interactions when combined with other antiseizure agents. It may help control aggression and disinhibition in traumatic brain injury (TBI), impulse control disorders in neurodegenerative conditions (particularly frontotemporal dementia), and behavioral dysregulation in individuals with developmental disabilities. Due to its significant teratogenic risk, it should be used cautiously in women of childbearing potential, with alternative mood stabilizers considered when appropriate.