Anticonvulsant Medications

Conditions treated with anticonvulsants

The first-line treatment for bipolar disorder is lithium, which is another mood stabilizer without any anticonvulsant effect. However, three anticonvulsants – carbamazepine, divalproex and lamotrigine – have also been shown to be effective in treating bipolar disorder.

Divalproex is considered a first-choice anticonvulsant treatment for mania and for rapid cycling (four or more manic episodes per year) bipolar disorder. Divalproex is also considered one of the first-choice anticonvulsant treatments for mixed episodes (episodes with features of both mania and depression) of bipolar disorder.

Lamotrigine is approved for long-term treatment of adults with bipolar disorder, and is considered a first-choice anticonvulsant treatment for patients with predominantly depressed episodes of bipolar disorder, and a second-choice anticonvulsant treatment for rapid cycling.

Many experts consider carbamazepine to be a first- or second-choice anticonvulsant treatment for mixed episodes and a second-choice anticonvulsant treatment for mania. However, unlike divalproex and lamotrigine, carbamazepine has not yet received approval from the U.S. Food and Drug Administration (FDA) for treatment of bipolar disorder. Physicians frequently prescribe it “off label,” a common practice in which FDA-approved medications are prescribed in a manner other than which they were originally intended.

Other newer anticonvulsants may be used to treat bipolar disorder, but usually in addition to first-line anticonvulsant treatments or when such treatments do not work. These include oxcarbazepine, topiramate, tiagabine and gabapentin.

Anticonvulsants such as carbamazepine, divalproex and topiramate are also used to treat personality disorders, especially borderline personality disorder. In addition, carbamazepine, divalproex and gabapentin are used to treat certain sleep disorders such as restless legs syndrome and periodic limb movement disorder.

Conditions of concern

Anticonvulsants are not typically prescribed in patients with liver or kidney disease. Some are not prescribed in patients with certain blood disorders (e.g., low platelet count). Others may be prescribed with caution and under close monitoring in these patients. Alcoholism may increase the risk of certain blood conditions (e.g., low sodium levels) in patients taking anticonvulsants.

Other potential conditions of concern with anticonvulsant use include:

• Anemia (deficiency of red blood cells)
• Diabetes (disease marked by an inability to control blood sugar)
• Glaucoma (disease marked by marked by increased pressure within the eyeball)
• Heart or blood vessel disease
• Pancreatitis (inflammation of the pancreas)
• Thalassemia (form of anemia found in people of Mediterranean descent)
• Urea cycle disorders (diseases that prevent removal of ammonia from the body)
• Urination problems

Females should use caution when considering use of divalproex. Studies in epilepsy patients have shown that shown that valproic acid (which is formed by divalproex in the body) may increase testosterone levels in teenage girls and may produce or worsen polycystic ovary syndrome (a condition that results in disruption in the reproductive cycle) in women who begin taking the medication before age 20.

Potential side effects of anticonvulsants

Side effects and their incidence levels vary depending on the type of anticonvulsant being taken. For example, up to 30 percent of patients taking carbamazepine may experience side effects.

Some of the more common side effects associated with anticonvulsant use include:

• Gastrointestinal complaints (e.g., nausea, vomiting, diarrhea). These common side effects generally improve if the medication is taken with milk or food. Lowering dosage levels or taking the medication at bedtime can also reduce these side effects.
• Central nervous system (CNS) complaints. These may include sedation, dizziness, drowsiness, blurred vision and lack of coordination. Lowering dosage levels can also reduce these side effects.
• Skin changes. Some anticonvulsants, especially lamotrigine, may cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease. Because of this link, most of these medications are discontinued when a rash develops. Anticonvulsant medications may also make a person’s skin more sensitive to sunlight.
• Changes in blood chemistry. Most anticonvulsant drugs require frequent blood tests to monitor their blood, chemical and compositional levels (e.g., calcium levels, white blood cell count, red blood cell count, liver enzymes). Most of these changes are harmless, but some can be quite dangerous. Divalproex can reduce the ability of the blood to clot in some patients. In rare cases, carbamazepine can result in significant and dangerous drops in levels of white or red blood cells.

Other common side effects of anticonvulsants include:

• Drowsiness
• Weight gain
• Hair loss
• Dizziness
• Incoordination
• Blurred vision
• Shaky hands (tremors)
• Liver disease or failure (rare)

CNS effects, cardiovascular effects and gastrointestinal effects are potential side effects associated with nearly all anticonvulsants. Other major side effects associated with specific anticonvulsants used for mental health disorders are as follows:

Drug or other interactions

Anticonvulsants are likely to interact with many other medications. In some cases, the anticonvulsant affects the action of the other medication, and in others, the action of the anticonvulsant is affected. Patients should consult their physicians before taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications.

In general, anticonvulsants add to the effects of alcohol and other central nervous system (CNS) depressants and increase drowsiness. Some other negative drug interactions depend on the type of anticonvulsants being taken.

For example, anticonvulsants such as carbamazepine and oxcarbazepine may reduce the effectiveness of many medications, including oral contraceptives (birth control pills). This makes it necessary for women of child-bearing age to use other forms of birth control when taking certain anticonvulsants.

Divalproex may increase the effectiveness of many medications, including anticoagulants and other mood stabilizers. Certain antibiotics may increase the levels of some anticonvulsants, resulting in a potentially toxic combination.

Other major drug groups that may interact poorly with anticonvulsants include antidepressants and heart medications.

Symptoms of anticonvulsant overdose

Symptoms of overdose can be similar to the medication’s side effects, but are usually more severe. Overdose of anticonvulsants is dangerous and can lead to coma or death. Common symptoms include:

• Nausea
• Vomiting
• Drowsiness
• Confusion
• Over- or underactive reflexes
• Seizures
• Trouble breathing

Regular monitoring of blood levels can help prevent anticonvulsants from building up to toxic levels. Blood levels may be monitored for the first month, and every one to three months thereafter.

Pregnancy use issues with anticonvulsants

Divalproex and carbamazepine have been associated with a variety of problems and birth defects, including nerve conditions and developmental delays. Children exposed to these anticonvulsant mood stabilizers in the womb may display low sugar levels in the blood (hypoglycemia) and liver dysfunction, among other problems. These two medications pass into breast milk and some adverse effects may occur. Therefore, women who are breastfeeding and using divalproex or carbamazepine must be monitored closely through blood tests. The safety of oxcarbazepine, a derivative of carbamazepine, requires further study.

Recent studies suggest that lamotrigine may increase the risk of cleft lip or palate when taken during the first trimester of pregnancy. In addition, the drug is excreted in breast milk and levels in infants can be high.

Topiramate appears to be safe to use during pregnancy and breastfeeding. No problems in infants exposed to this medication in the womb or through breast milk have been discovered.

The effects of gabapentin and tiagabine during pregnancy and breastfeeding are unknown, although tiagabine is known to be excreted in the breast milk of rats. For this reason, these drugs should be used with caution.

Child use issues

The side effects of anticonvulsant medications may be more pronounced in children. These include abdominal or stomach cramps, nausea and/or vomiting, tiredness and/or weakness, and yellow eyes or skin (jaundice). Children up to 2 years of age with other medical problems or who are taking more than one anticonvulsant may have the greatest risk for side effects.

Elderly use issues

Anticonvulsants may not pass as quickly through the bodies of elderly patients as they do in younger patients. As a result, elderly patients may be especially likely to experience certain side effects associated with anticonvulsants, including confusion, restlessness and nervousness, altered heartbeat (i.e., irregular, pounding or slow) or chest pain.

Lower dosage levels of anti-convulsant medications can help reduce the chances of side effects.