Anticonvulsants and the Treatment of Bipolar Disorder

By Candida Fink, Joe Kraynak

Your brain and central nervous system form an intricate power grid that carries very low-level electricity. With serious central nervous system malfunctions, as in epilepsy, neurons misfire to such an extent that they can cause seizures. Anticonvulsants — including valproate, commonly known as valproic acid (Depakote) — appear to reduce seizures, at least in part by regulating neuron firing.

The mechanisms of bipolar aren’t the same as seizures, but a number of anticonvulsants are effective in treating some symptoms of bipolar disorder. Stabilization of neuron cell firing may play a role, but researchers are studying other potential mechanisms of action, including effects on genetic expression.

The following table lists the main medications in the anticonvulsant class, along with their doses, benefits, and possible side effects.

Potential Benefits and Side Effects of Anticonvulsants
Generic Name Brand Names Average
Adult Dose
Therapeutic Blood Level Potential Benefits Some Possible Side Effects*
Carbamazepine Tegretol
Carbatrol
Epitol
Equetro
400 to 1,600 mg/day or 10 to 30 mg/kg/day 4 to 12 mcg/mL is the range for seizures; therapeutic level for
mania is less well established; more than 15 mcg/mL is considered
toxic
Antimanic; third choice after trials of lithium and valproate;
doesn’t cause significant weight gain in most patients; may help
control aggression and violent outbursts.
Can reduce effectiveness of birth control pills; blood cell
problems; reduced B-12 and folate levels; liver problems; blurry
vision; dizziness; nausea; risk of Stevens-Johnson syndrome, a
severe skin and mucus membrane reaction that can be lethal (much
higher in individuals of Han Chinese descent due to a genetic
effect on metabolism); effects on liver enzymes cause interactions
with many other medications.
Divalproex sodium
Valproate
Valproic acid
Depakote
Depakene
1,000 to 2,000 mg/day or 25 to 60 mg/kg/day, but upper limit
varies according to amount needed to establish therapeutic blood
level.
50 to 125 mcg/mL (risk of toxicity increases above this
level).
Antimanic; may prevent or reduce recurrent episodes; possibly
some weak antidepressant activity.
Pancreas and liver problems; weight gain; sedation; nausea;
possible fertility problems in females; hair loss; elevated ammonia
levels.
Lamotrigine Lamictal 25 to 200 mg/day; must ramp up very slowly to reduce likelihood
of Stevens-Johnson syndrome; dosing must start lower and go slower
if given with valproate.
N/A Reduces mood cycle frequency; strong antidepressant properties;
not usually associated with weight gain; doesn’t reduce acute
mania.
Stevens-Johnson syndrome; may reduce effectiveness of some
types of birth control pills; nausea and vomiting; dizziness;
blurred vision; headache; insomnia or other sleep changes; if
taking with valproate, must start with much lower doses of
lamotrigine and increase even more slowly than usual.

mg/day = milligrams per day; mg/kg/day = milligrams per kilogram of body weight per day; mEq/L = milliequivalents per liter.

* Other side effects may occur that are not listed.

Valproate is commonly used as a first-line treatment for acute mania, as well as for maintenance therapy. Carbamazepine (Tegretol) has also proven effective for mania and maintenance care. Oxcarbemazapine (Trileptal) is a medication closely related to carbamazepine but with fewer side effects. It’s being used in place of carbamazepine, but the research on its effectiveness is still limited. Lamotrigine (Lamictal) is growing in popularity because of its effectiveness in mood maintenance and potential for helping to alleviate depression, but it’s not effective in treating acute mania.

Topiramate (Topamax) is an anticonvulsant that was sometimes used to treat bipolar disorder, but studies have shown that it to be ineffective. It often reduces appetite, though, so doctors sometimes use it to help reduce weight gain associated with other medications for bipolar disorder. Gabapentin (Neurontin) is another medication used for seizure that was once thought to be helpful in bipolar disorder, but studies have shown it to be ineffective. It’s sometimes used to treat anxiety (see the later section on anti-anxiety medications).

Researchers are looking into other anticonvulsants such as zonisamide (Zonegran), levetiracetam (Keppra), and tiagabine (Gabitril) for use in bipolar disorder, but at this time the research is scanty with no support for their use.

Withdrawing an anticonvulsant too quickly can cause seizures. Always consult your doctor before you stop or decrease a medication.