Lithium (Eskalith, Lithobid), valproate (Depakene, Depakote) and carbamazepine (Carbatrol, Epitol, Tegretol) are referred to as mood-stabilizing drugs. Lithium and valproate are considered first-choice drugs for treating acute manic episodes and preventing recurrences of mania and depression in bipolar patients. It is unclear how they work. Overall, about 50 percent to 80 percent of patients have some response to either drug. They are generally safe when used correctly. Although it can be difficult to predict who will benefit from lithium, factors associated with a good response include a family history of bipolar disorder; a previously favorable response to lithium; having only a few prior episodes of mania and a history of full relief from symptoms between episodes. Maximal response to the drug usually takes two to three weeks (patients may also be given an antianxiety or antipsychotic drug to control manic symptoms during this time). Lithium is not used in patients with seriously impaired kidney function, and lower doses are prescribed in elderly people. Blood levels of lithium are measured regularly to assure adequate doses and to avoid the dangerous effects of toxic levels. Common adverse effects of lithium include increased thirst and urination, nausea and vomiting, loss of appetite, diarrhea, a fine tremor of the hands and muscle weakness. Muscle twitching, coarse tremor, slurred speech, drowsiness, disorientation, confusion, seizures and coma can result from toxic blood levels of lithium. Diuretics, such as furosemide (Lasix) and hydrochlorothiazide (Esidrix) and nonsteroidal anti-inflammatory drugs, such as ibuprofen (Advil, Motrin, Nuprin, and Rufen), increase the risk of toxicity. Long-term lithium treatment can compromise kidney function. Persistent thirst and excessive urination, which occur in about 25 percent of those taking lithium, are due to lithium's effect on the kidneys. Also, by decreasing the secretion of the thyroid hormone, lithium can produce hypothyroidism. These effects are usually reversed once lithium is discontinued. Although less research is available on valproate and carbamazepine than on lithium, one recent study found that 48 percent of patients taking valproate for acute mania had at least a 50 percent reduction in manic symptoms - a rate similar to that for lithium. Thus far, it appears that valproate is as effective for rapid mood-cycling bipolar disorder (four or more changes in mood state in one year) as it is for more traditional forms of mania. (Lithium may not work as well in rapid cycling cases.) Carbamazepine also appears to be effective, but currently there are no data comparing it with lithium. This drug appears less effective than valproate for relieving symptoms of bipolar disorder and also has more dangerous long-term side effects. Thus, it is mainly used in combination with lithium or on its own when other drugs fail, especially in cases of rapid cycling or mixed episodes of mania. (In mixed episodes of mania, patients experience both manic and depressive symptoms at the same time, such as a low, irritable mood in combination with high energy and racing thoughts.) Lithium is the only one of these drugs proven to be effective for maintenance treatment. Most of the side effects of valproate and carbamazepine can be relieved by dose adjustment. However, blood tests are required to monitor possible dangerous effects of valproate on the bone marrow, liver and pancreas. Valproate should not be used in people who have an impaired ability to produce urea, as this can lead to a dangerous buildup of ammonia in the blood. Carbamazepine can cause aplastic anemia (cessation of blood cell formation by the bone marrow), agranulocytosis (loss of white blood cell production by the bone marrow), liver failure, dermatitis and pancreatitis (inflammation of the pancreas). Although these side effects are rare, laboratory tests cannot reliably predict their occurrence. Patients should be aware of two important signs of trouble for both drugs - easy bruising and jaundice (a sign of liver problems). Last Updated: 5/19/2003
The Johns Hopkins University 1996-2003. All rights reserved. This information is not intended to provide advice on personal medical matters, nor is it intended to be a substitute for consultation. |
