Depakote: A Proven Mood Stabilizer for Bipolar Disorder
Depakote
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Synonyms
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Depakote (divalproex sodium) is an established anticonvulsant medication with primary FDA approval for the treatment of manic episodes associated with bipolar disorder. It functions by increasing gamma-aminobutyric acid (GABA) levels in the brain, promoting neuronal stability and reducing excessive electrical activity. This mechanism underlies its efficacy in managing the extreme mood swings characteristic of bipolar mania. Clinicians frequently prescribe Depakote for its demonstrated ability to reduce symptom severity, prevent relapse, and support long-term mood stabilization, often as a cornerstone of maintenance therapy.
Features
- Active ingredient: Divalproex sodium, a stable coordination compound of sodium valproate and valproic acid
- Available formulations: Delayed-release tablets, extended-release tablets, and sprinkle capsules
- Standard strengths: 125 mg, 250 mg, 500 mg delayed-release tablets; 500 mg extended-release tablets
- Proprietary enteric coating to minimize gastric irritation
- Bioequivalent to valproic acid but with improved gastrointestinal tolerability
Benefits
- Effectively reduces the severity and frequency of manic episodes in bipolar I disorder
- Provides long-term mood stabilization to prevent relapse into mania or depression
- Offers flexible dosing options with multiple formulations for individualized treatment
- Demonstrates a rapid onset of action in acute manic episodes, often within days
- Serves as a viable alternative for patients intolerant to lithium therapy
- May reduce the frequency of migraine headaches when used prophylactically
Common use
Depakote is primarily indicated for the treatment of manic episodes associated with bipolar disorder. It is commonly used as monotherapy or in combination with other psychotropic medications for acute management and maintenance therapy. Off-label uses include migraine prophylaxis, adjunctive treatment for other seizure disorders, and management of agitation in dementia. Clinical practice often involves therapeutic drug monitoring to maintain serum valproic acid levels between 50-125 μg/mL for optimal efficacy while minimizing adverse effects.
Dosage and direction
Initial dosing for acute mania typically begins at 750 mg daily in divided doses, with increases of 5-10 mg/kg/day every 1-3 days based on clinical response and tolerability. The target therapeutic range is usually achieved with doses of 1000-2500 mg daily. Extended-release formulations allow for once-daily dosing, while delayed-release tablets are typically administered twice daily. Dosage should be titrated slowly to minimize gastrointestinal adverse effects. Administration with food may enhance tolerability but does not significantly affect absorption. Regular monitoring of serum concentrations is recommended, particularly during dose adjustments or when adding interacting medications.
Precautions
Regular monitoring of liver function tests, complete blood count, and ammonia levels is essential, particularly during the initial six months of therapy. Patients should be cautioned about the potential for weight gain and advised regarding nutritional monitoring. Enhanced tremor monitoring is recommended, as this may signal toxicity. Women of childbearing potential require comprehensive counseling regarding teratogenic risks and need for effective contraception. Cognitive effects including sedation and impaired alertness may affect operating machinery or driving. Pancreatitis, though rare, requires immediate evaluation if abdominal pain, nausea, or vomiting develop.
Contraindications
Depakote is contraindicated in patients with known hypersensitivity to valproate, divalproex sodium, or any component of the formulation. It must not be used in patients with significant hepatic impairment or urea cycle disorders due to the risk of hyperammonemia. Concomitant use with other hepatotoxic drugs requires extreme caution. The medication is contraindicated in patients with known mitochondrial disorders caused by POLG mutations. Pregnancy constitutes a relative contraindication except in cases where benefits substantially outweigh documented teratogenic risks.
Possible side effect
Common adverse effects (≥10% incidence) include nausea, somnolence, dizziness, vomiting, asthenia, abdominal pain, and tremor. Less frequent effects (1-10%) may involve diarrhea, increased appetite, weight gain, alopecia, nystagmus, diplopia, amblyopia, and thrombocytopenia. Serious but rare (<1%) adverse reactions include hepatotoxicity, pancreatitis, hyperammonemic encephalopathy, suicidal ideation, and severe dermatological reactions. Endocrine effects such as polycystic ovarian syndrome and irregular menses have been reported with long-term use. Platelet aggregation abnormalities may occur even without overt thrombocytopenia.
Drug interaction
Depakote demonstrates significant protein binding displacement interactions with phenytoin and warfarin. It inhibits the metabolism of lamotrigine, phenobarbital, and carbamazepine-epoxide, necessitating dose adjustments. Enzyme-inducing antiepileptics (carbamazepine, phenytoin, phenobarbital) may decrease valproate levels by 30-50%. Concomitant use with clonazepam may precipitate absence status. Aspirin and other highly protein-bound drugs may increase free valproate concentrations. Selective serotonin reuptake inhibitors may lower the seizure threshold. Cholestyramine may reduce absorption through binding in the gastrointestinal tract.
Missed dose
If a dose is missed, it should be taken as soon as possible unless it is接近 the time for the next scheduled dose. In that case, the missed dose should be skipped, and the regular dosing schedule resumed. Patients should never double the dose to make up for a missed administration. Consistent timing is particularly important for extended-release formulations to maintain stable serum concentrations. If multiple doses are missed, consultation with the prescribing physician is recommended before resuming therapy, as dose retitration may be necessary.
Overdose
Valproate overdose presents a medical emergency characterized by somnolence, heart block, deep coma, and metabolic acidosis. Serum levels exceeding 150 μg/mL constitute toxicity, while levels above 450 μg/mL may be fatal. Management includes gastric lavage if presentation occurs within 1-2 hours of ingestion. Activated charcoal may be effective even with delayed-release formulations. Hemodialysis effectively removes valproate and corrects metabolic abnormalities. Naloxone has reversed CNS depression in some cases, though mechanism remains unclear. Supportive care with particular attention to respiratory status, electrolyte balance, and ammonia levels is essential.
Storage
Store at controlled room temperature (20-25°C or 68-77°F) in a tightly closed container. Protect from moisture and light. Keep all medications out of reach of children and pets. Do not transfer sprinkle capsules to other containers, as this may affect the integrity of the enteric coating. Do not use if the blister pack or bottle seal has been broken or shows signs of tampering. Proper disposal of 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. Individual response to medication varies based on genetic factors, concomitant conditions, and other medications. Depakote should only be used under the supervision of a qualified healthcare provider who can monitor therapy and adjust treatment based on clinical response and laboratory parameters. Never initiate, adjust, or discontinue medication without consulting your prescribing physician. The full prescribing information contains complete details regarding indications, warnings, and precautions.
Reviews
Clinical trials demonstrate Depakote’s efficacy in achieving response rates of 48-52% in acute mania compared to 25-30% with placebo. Maintenance studies show significant prolongation of time to any mood episode compared to placebo. Many clinicians report particular success in patients with rapid-cycling bipolar disorder and those with mixed features. Patient-reported outcomes often note improved functional capacity and reduced hospitalization rates. However, weight gain and metabolic effects remain significant concerns in long-term management. Comparative effectiveness studies suggest similar efficacy to lithium in acute mania but potentially better tolerability in certain patient populations.