Bipolar Medication Spotlight: Depakote (Valproic Acid)

By Candida Fink MD

With this post, we continue our biweekly series on medications used to bipolar disorder and related symptoms. We launched the series with a post on lithium – the standard bearer for the so-called mood stabilizers .

The term mood stabilizer can mean one or two things – it can be anti-manic and/or it can reduce the frequency of cycles, both manic and depressed. Some of these medications treat depressive episodes as well (lithium, for example) but that is not the primary effect of a mood stabilizer.

This week, we turn our attention to anti-seizure medications, originally developed to prevent seizures in people with epilepsy. Over the coming weeks, we will be covering several of the most common anti-seizure meds used to treat bipolar-disorder-related symptoms, including Depakote (valproic acid), Lamictal (lamotrigene), Tegretol (carbemazapine), Trileptal (oxcarbazepine), Topomax (topiramate), and Neurontin (gabapentin).

Some of these anti-seizure medications have been found to be effective in managing some symptoms of bipolar disorder. The best known medication in this class is Depakote (also known as valproate, valproic acid, or divalproex).

It’s not clear why some anti-seizure medications have benefit in bipolar disorder. Seizures are caused by “short circuits” in the brain that lead to, basically, electrical storms. Mania, which is the most common target of mood stabilizers, lasts much longer than a seizure, but there may be some similar types of instability in the neurons of the brain shared by seizures and mania.

Depakote and lithium are considered first-tier medications for treating mania. They’re among the “big guns” that doctors often prescribe for people who become hospitalized for acute mania. These meds tend to quell the mania in a hurry, in addition to preventing future episodes. Following are some of the unique benefits Depakote offers:

• It treats mania, and is particularly effective in treating acute mania.
• It’s a good alternative to lithium for people who don’t respond well to lithium.
• It’s generally safer than lithium, because it has a greater range between the therapeutic and toxic levels.
• Some studies show that it may be better than other mood stabilizers at treating mixed episodes or rapid cycling.
• Depakote is often used as a maintenance medication – to help reduce frequency of cycles. The data on its effectiveness in this capacity is mixed.

Although Depakote is generally safer than lithium, it’s not exactly the perfect medication for bipolar disorder. For one, it hasn’t been shown to be very effective in treating the depression pole of bipolar disorder. If you experience depression in addition to mania, you may need to take an antidepressant, as well. Depakote also carries the following potential side effects:

• Pancreas and liver problems
• Weight gain
• Sedation
• Nausea
• Possible fertility problems in females
• Hair loss
• Platelet problems, which could result in increased bleeding

As with lithium, you need to maintain blood levels (the concentration of Depakote in the blood) at a therapeutic level below the level of toxicity. If your Depakote level dips below its therapeutic level, the drug may become less effective. If it rises too high, the drug can become toxic, causing possible damage to the pancreas or liver. So remember:

• Always take the prescribed dose. Appropriate doses can vary widely from person to person – even people of similar weights. The blood level is the important number in the case of Depakote. So don’t worry if your dose is very different from someone else you know.
• Your doctor may start you on higher doses (loading doses) early in your treatment to more quickly establish a blood level in the therapeutic range.
• Your doctor may prescribe Depakote ER (extended release), so you won’t have to take the medication so often. Don’t use standard Depakote in place of the ER type or vice versa; the two are not interchangeable.
• Make sure your doctor prescribes regular blood tests to check your valproate levels – at least every few months (more regularly when you first start taking it). The therapeutic level of valproate is between 50 and 125 mmol/litre.
• Your doctor may also order additional blood and urine tests particularly to check for liver, pancreas, and platelet abnormalities, which are rare.
• Valproate levels can rise as you lose fluid, so be wary of hot weather and vigorous exercise, and limit your consumption of diuretics, including coffee and alcohol.

Caution: Never stop taking any medication cold turkey, especially an anti-seizure medication. Withdrawing an anti-seizure medication too quickly can actually cause seizures. Always consult your doctor before you stop or decrease your medication.

If you’ve taken Depakote (or other forms of valproate) for bipolar disorder or are a doctor who has prescribed it, please share your experiences, insights, and observations.

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