Depakote: Comprehensive Mood Stabilizer and Anticonvulsant Therapy
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Synonyms
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Depakote (divalproex sodium) is an established antiepileptic and mood-stabilizing medication with proven efficacy in managing complex neurological and psychiatric conditions. As an enteric-coated formulation, it offers improved gastrointestinal tolerability while delivering consistent therapeutic levels of valproic acid, the active metabolite. This medication represents a cornerstone in treatment algorithms for bipolar disorder, migraine prophylaxis, and various seizure disorders, providing clinicians with a versatile therapeutic option backed by decades of clinical evidence and real-world experience.
Features
- Divalproex sodium formulation with enteric coating for reduced gastric irritation
- Multiple dosage forms: delayed-release tablets, extended-release tablets, and sprinkle capsules
- Therapeutic range: 50-125 μg/mL for optimal efficacy and safety monitoring
- Protein binding approximately 90%, primarily to albumin
- Half-life ranging from 9-16 hours in adults, requiring twice-daily dosing for most formulations
- Hepatic metabolism primarily via glucuronidation and mitochondrial β-oxidation
Benefits
- Provides effective stabilization of mood episodes in bipolar disorder, reducing frequency and severity of manic episodes
- Demonstrates broad-spectrum anticonvulsant activity against multiple seizure types
- Offers preventive migraine benefits with significant reduction in attack frequency
- Maintains therapeutic levels with consistent pharmacokinetic profile
- Features flexible dosing options to accommodate individual patient needs
- Supports long-term treatment adherence through established safety profile
Common use
Depakote is primarily indicated for the treatment of complex partial seizures, monotherapy and adjunctive therapy for simple and complex absence seizures, and adjunctive treatment of multiple seizure types that include absence seizures. In psychiatric practice, it is approved for the treatment of manic episodes associated with bipolar disorder and for migraine prophylaxis. Off-label uses include treatment of neuropathic pain, agitation in dementia, and impulse control disorders. The medication is particularly valuable in cases where lithium is contraindicated or poorly tolerated, and for patients with mixed or rapid-cycling bipolar features.
Dosage and direction
Initial dosing for epilepsy typically begins with 10-15 mg/kg/day, increasing by 5-10 mg/kg/week until optimal clinical response is achieved. For bipolar mania, initial dosing is 750 mg daily in divided doses, with target doses of 1000-1500 mg/day. Migraine prophylaxis typically initiates at 250 mg twice daily, with effective doses ranging from 500-1000 mg/day. The delayed-release tablets should be swallowed whole without chewing to maintain enteric coating integrity. Administration with food may minimize gastrointestinal discomfort. Dose adjustments are necessary in elderly patients, those with hepatic impairment, and when combining with other highly protein-bound medications.
Precautions
Regular monitoring of liver function tests, complete blood count, and valproic acid levels is essential, particularly during the initial six months of therapy. Patients should be cautioned about the potential for hepatotoxicity, especially in children under two years, those with metabolic disorders, or individuals on multiple anticonvulsants. Pancreatitis risk, though rare, requires immediate medical attention for unexplained abdominal pain, nausea, or vomiting. Thrombocytopenia and impaired platelet function may occur, necessitating caution with surgical procedures. Teratogenic risks mandate effective contraception in women of childbearing potential. Cognitive effects, including sedation and tremor, may impair operating machinery or driving.
Contraindications
Depakote is contraindicated in patients with known hypersensitivity to valproic acid, divalproex sodium, or any component of the formulation. It is prohibited in patients with significant hepatic impairment or active liver disease. Those with known urea cycle disorders should avoid this medication due to risk of hyperammonemia. Concomitant use with other drugs that significantly elevate ammonia levels is contraindicated. The medication is not recommended during pregnancy for migraine prophylaxis due to teratogenic risk, and requires careful risk-benefit assessment for other indications.
Possible side effect
Common adverse effects include nausea (31%), somnolence (30%), dizziness (25%), vomiting (23%), and asthenia (20%). Gastrointestinal disturbances often diminish with continued therapy. Weight gain affects approximately 20% of patients, while tremor occurs in 15-25% of users. Alopecia (hair thinning) may develop but is typically reversible. Less frequent but serious effects include hepatotoxicity (0.01-0.1%), pancreatitis (<0.1%), thrombocytopenia (5-10%), and hyperammonemia (5-10%). Endocrine effects may include irregular menses and polycystic ovary syndrome in premenopausal women. Cognitive effects such as confusion or memory impairment occur more frequently at higher doses.
Drug interaction
Depakote demonstrates significant interaction potential due to enzyme inhibition and protein binding displacement. It inhibits CYP2C9, CYP2C19, and UGT enzymes, increasing levels of phenobarbital, lamotrigine, and tricyclic antidepressants. Concomitant use with carbapenem antibiotics reduces valproate levels by 60-100%. Aspirin and other highly protein-bound drugs may displace valproate from binding sites. Enzyme inducers such as carbamazepine, phenytoin, and rifampin may decrease valproate levels by 30-50%. The combination with clonazepam may precipitate absence status epilepticus. Alcohol and other CNS depressants potentiate sedative effects.
Missed dose
If a dose is missed, it should be taken as soon as possible unless it is nearly time for the next scheduled dose. Doubling doses to make up for missed medication should be avoided due to increased risk of side effects. Patients should maintain regular dosing schedules to minimize fluctuations in serum concentrations. For extended-release formulations, consistency in administration time is particularly important to maintain stable drug levels. If multiple doses are missed, medical consultation is recommended rather than attempting to compensate with larger subsequent doses.
Overdose
Valproate overdose presents with symptoms including somnolence, heart block, deep coma, and metabolic acidosis. Serum levels exceeding 150 μg/mL constitute serious toxicity, while levels above 450 μg/mL may be fatal. Management includes gastric lavage if presented within 1-2 hours of ingestion, activated charcoal administration, and supportive care. Hemodialysis may be effective in severe cases due to valproate’s relatively low molecular weight and limited protein binding at toxic concentrations. Naloxone has reversed CNS depression in some cases. Specific antidotes are unavailable, making supportive care and enhanced elimination the mainstays of treatment.
Storage
Store at controlled room temperature (20-25°C or 68-77°F) in a dry place protected from light and moisture. Keep containers tightly closed and away from excessive heat or humidity. Do not remove desiccant packets from packaging. Keep all medications out of reach of children and pets. Do not transfer tablets to alternative containers that compromise the enteric coating protection. Proper disposal of expired or unused medication through take-back programs is recommended to prevent accidental ingestion or environmental contamination.
Disclaimer
This information is provided for educational purposes only and does not constitute medical advice. Treatment decisions must be made by qualified healthcare professionals considering individual patient circumstances. The prescribing physician should be consulted for specific dosage recommendations and monitoring requirements. Actual clinical effects may vary among individuals. Patients should not alter or discontinue medication without professional guidance. Full prescribing information including boxed warnings should be reviewed before initiation of therapy.
Reviews
Clinical studies demonstrate response rates of 60-70% in acute mania, with significant improvement in Young Mania Rating Scale scores. Epilepsy trials show 50-60% reduction in seizure frequency in refractory patients. Migraine studies indicate 50% reduction in headache frequency in approximately 40-50% of patients. Long-term maintenance therapy in bipolar disorder shows reduced relapse rates compared to placebo. Real-world evidence supports sustained efficacy over years of treatment, though individual responses vary. Patient-reported outcomes highlight benefits in mood stability and quality of life, balanced against concerns regarding weight gain and cognitive effects.