Understanding Depakote (Valproic Acid) for Bipolar Disorder
Introduction:
Bipolar disorder is a complex mental health condition characterized by significant mood swings, including manic and depressive episodes. Depakote (Valproic Acid, VPA) is a medication that has been widely used in the treatment of this condition. This handout aims to provide an easy-to-understand overview of Depakote, its effectiveness, dosing guidelines, potential side effects, contraindications, FDA approval status, and off-label benefits supported by research.
Efficacy:
Clinical trials and research studies have shown that Depakote is effective in treating manic episodes associated with bipolar disorder. It has also been established that Depakote can help prevent relapse in bipolar disorder, including in depressive episodes.
Dosing Guidelines:
Adults: The starting dose for adults is typically between 25 to 60 mg/kg per day. Dosing should be adjusted based on therapeutic response and plasma levels, aiming for a trough plasma concentration between 50 and 125 mcg/ml.
Pediatrics: Lower starting doses are recommended for pediatric patients, and adjustments should be made cautiously.
Preference for VPA ER Over Immediate Release: Extended-release (ER) formulations of VPA are often preferred over immediate-release forms due to their more stable plasma levels, once-daily dosing, and potentially fewer side effects.
Serum Levels and Other Laboratory Studies:
When initiating or adjusting the dose of Valproic Acid (VPA) ER, we conduct lab testing 8 to 10 days later to accurately measure trough levels of the serum concentration, ensuring the test is performed 12-14 hours after the last dose. This timing is crucial for obtaining accurate trough levels, which are essential for assessing the medication's effectiveness.
For acute mania, we aim for serum levels above 90 mcg/ml, while during the maintenance phase, the target is between 75 and 100 mcg/ml to optimize treatment outcomes.
Other Important Labs:
Liver Function Tests (LFTs): These are crucial due to the risk of hepatotoxicity associated with VPA. Monitoring should occur prior to therapy and at frequent intervals thereafter, especially during the first six months of treatment.
Complete Blood Count (CBC) with Differential: This test is important to monitor for potential hematologic effects such as thrombocytopenia and leukopenia.
Ammonia Levels (NH3+): Although routine monitoring of ammonia is not recommended, it may be necessary if the patient exhibits sudden mental status changes or other symptoms indicative of hyperammonemia.
When to Take It:
We usually use Depakote ER, or extended release, which helps minimize side effects and missed doses. This is given each night, prior to bed. It does not have to be taken with food.
Do not open the capsule, as it’s a slow release mechanism.
Depakote Preparations:
Depakote Sprinkle Capsules: Delayed release, can be sprinkled on food.
Depakote DR: Delayed release, should not be chewed or crushed/cut/opened.
Depakote ER: Extended release, once per day, should not be chewed or crushed/cut/opened.
Valproic Acid Oral Solution and Injectable Form.
Medications to Avoid When Taking Depakote:
Here are the top 10 medications to avoid using with Depakote (divalproex sodium), along with brief explanations of why they are problematic. For a complete list, visit here.
Aspirin (Acetylsalicylic Acid): Can increase the blood levels of Depakote, potentially leading to toxicity.
Carbamazepine (Tegretol): May decrease the effectiveness of Depakote and increase the risk of side effects.
Clonazepam (Klonopin): Increases the risk of sedation and respiratory depression when combined with Depakote.
Erythromycin: This antibiotic can increase Depakote levels, raising the risk of toxicity.
Ethosuximide (Zarontin): Can alter the levels of Depakote in the blood, affecting efficacy.
Rifampin: Significantly decreases the blood levels of Depakote, reducing its effectiveness.
Topiramate (Topamax): Increases the risk of hyperammonemia and encephalopathy when used with Depakote.
Warfarin (Coumadin): Depakote can affect warfarin levels and increase bleeding risk.
Zidovudine (AZT): Can lead to increased zidovudine toxicity when used with Depakote.
Other mood stabilizers like Lithium: Can increase the risk of side effects such as tremors, nausea, and cognitive disturbances.
These interactions can lead to increased side effects, reduced effectiveness of treatments, or other complications, making it crucial to manage these combinations carefully under medical supervision.
Potential Side Effects:
Common side effects (in the 5% range) of Depakote include abdominal and back pain (often temporary), hair loss (see our blog on how to treat this side effect), blurred vision, dizziness, and physical weakness or lack of energy.
Less common side effects include tremors, weight gain, and changes in mood or behavior.
More serious side effects can include liver damage, pancreatitis, confusion from elevated ammonia (NH3+), and blood disorders.
A full list of potential side effects can be found here.
Potential Contraindications Including Pregnancy:
Depakote is contraindicated in pregnancy due to the risk of birth defects and decreased IQ in the offspring.
It is also contraindicated in patients with liver disease or significant hepatic impairment, and in those with known hypersensitivity to the drug.
A full list of other contraindications can be found here.
FDA Approval Information:
Depakote is FDA-approved for the treatment of manic episodes associated with bipolar disorder, as well as for epilepsy and migraine prophylaxis. Its use in bipolar disorder is supported by clinical trials demonstrating efficacy in the acute management of manic episodes.
Off-Label Benefits:
In addition to its approved uses, Depakote has been studied for off-label benefits, including Disruptive Mood Dysregulation Disorder (DMDD), Intermittent Explosive Disorder (IED), outbursts related to Autism, the prevention of migraine headaches, and as an adjunct in the treatment of schizophrenia.
While these uses are supported by some research, they are considered off-label, and decisions about their use should be made on an individual basis.
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/018723s066lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018723s037lbl.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599863/
https://www.ncbi.nlm.nih.gov/books/NBK559112/
