MEDICATIONS: ANTIMANIC MEDICATIONS

Bipolar disorder is characterized by cycling mood changes: severe highs (mania) and lows (depression). Episodes may be predominantly manic or depressive, with normal mood between episodes. Mood swings may follow each other very closely, within days (rapid cycling) or may be separated by months to years. The "highs" and "lows" may vary in intensity and severity and can co-exist in "mixed" episodes.

When people are in a manic "high," they may be overactive, overly talkative, have a great deal of energy and have much less need for sleep than normal. They may switch quickly from one topic to another, as if they cannot get their thoughts out fast enough. Their attention span is often short, and they can be easily distracted. Sometimes people who are "high" are irritable or angry and have false or inflated ideas about their position or importance in the world. They may be very elated, and full of grand schemes that might range from business deals to romantic sprees. Often, they show poor judgment in these ventures. Mania, untreated, may worsen to a psychotic state.

In a depressive cycle the person may have a "low" mood with difficulty concentrating; lack of energy, with slowed thinking and movements; changes in eating and sleeping patterns (usually increases of both in bipolar depression); feelings of hopelessness, helplessness, sadness, worthlessness and guilt; and, sometimes, thoughts of suicide.

Lithium

The medication used most often to treat bipolar disorder is lithium. Lithium evens out mood swings in both directions — from mania to depression, and depression to mania — so it is used not just for manic attacks or flare-ups of the illness but also as an ongoing maintenance treatment for bipolar disorder.

Although lithium will reduce severe manic symptoms in about five to 14 days, it may be weeks to several months before the condition is fully controlled. Antipsychotic medications are sometimes used in the first several days of treatment to control manic symptoms until the lithium begins to take effect. Antidepressants may be added to lithium during the depressive phase of bipolar disorder. If given in the absence of lithium or another mood stabilizer, antidepressants may provoke a switch into mania in people with bipolar disorder.

A person may have one episode of bipolar disorder and never have another, or be free of illness for several years. But for those who have more than one manic episode, doctors usually give serious consideration to maintenance (continuing) treatment with lithium.

Some people respond well to maintenance treatment and have no further episodes. Others may have moderate mood swings that lessen as treatment continues, or have less frequent or less severe episodes. Unfortunately, some people with bipolar disorder may not be helped at all by lithium. Response to treatment with lithium varies, and it cannot be determined beforehand who will or will not respond to treatment.

Regular blood tests are an important part of treatment with lithium. If too little is taken, lithium will not be effective. If too much is taken, a variety of side effects may occur. The range between an effective dose and a toxic one is small. Blood lithium levels are checked at the beginning of treatment to determine the best lithium dosage. Once a person is stable and on a maintenance dosage, the lithium level should be checked every few months. How much lithium people need to take may vary over time, depending on how ill they are, their body chemistry and their physical condition.

Side Effects of Lithium
When people first take lithium, they may experience side effects such as drowsiness, weakness, nausea, fatigue, hand tremor or increased thirst and urination. Some may disappear or decrease quickly, although hand tremor may persist. Weight gain may occur. Dieting will help, but crash diets should be avoided because they may raise or lower the lithium level. Drinking low-calorie or no-calorie beverages, especially water, will help keep weight down. Kidney changes — increased urination and, in children, enuresis (bed wetting) — may develop during treatment. These changes are generally manageable and are reduced by lowering the dosage. Because lithium may cause the thyroid gland to become underactive (hypothyroidism) or sometimes enlarged (goiter), thyroid function monitoring is a part of the therapy. To restore normal thyroid function, thyroid hormone may be given along with lithium.

Because of possible complications, doctors either may not recommend lithium or may prescribe it with caution when a person has thyroid, kidney or heart disorders, epilepsy or brain damage. Women of childbearing age should be aware that lithium increases the risk of congenital malformations in babies. Special caution should be taken during the first three months of pregnancy.

Anything that lowers the level of sodium in the body — reduced intake of table salt, a switch to a low-salt diet, heavy sweating from an unusual amount of exercise or a very hot climate, fever, vomiting or diarrhea — may cause a lithium buildup and lead to toxicity. It is important to be aware of conditions that lower sodium or cause dehydration and to tell the doctor if any of these conditions are present so the dose can be changed.

Lithium, when combined with certain other medications, can have unwanted effects. Some diuretics — substances that remove water from the body — increase the level of lithium and can cause toxicity. Other diuretics, like coffee and tea, can lower the level of lithium. Signs of lithium toxicity may include nausea, vomiting, drowsiness, mental dullness, slurred speech, blurred vision, confusion, dizziness, muscle twitching, irregular heartbeat and, ultimately, seizures. A lithium overdose can be life-threatening. People who are taking lithium should tell every doctor who is treating them, including dentists, about all medications they are taking.

With regular monitoring, lithium is a safe and effective drug that enables many people, who otherwise would suffer from incapacitating mood swings, to lead normal lives.

Anticonvulsants

Some people with symptoms of mania who do not benefit from or would prefer to avoid lithium have been found to respond to anticonvulsant medications commonly prescribed to treat seizures.

The anticonvulsant valproic acid (Depakote, divalproex sodium) is the main alternative therapy for bipolar disorder. It is as effective in non-rapid-cycling bipolar disorder as lithium and appears to be superior to lithium in rapid-cycling bipolar disorder. Although valproic acid can cause gastrointestinal side effects, the incidence is low. Other adverse effects occasionally reported are headache, double vision, dizziness, anxiety or confusion. Because in some cases valproic acid has caused liver dysfunction, liver function tests should be performed before therapy and at frequent intervals thereafter, particularly during the first six months of therapy.

Studies conducted in Finland in patients with epilepsy have shown that valproic acid may increase testosterone levels in teenage girls and produce polycystic ovary syndrome (POS) in women who began taking the medication before age 20. POS can cause obesity, hirsutism (body hair) and amenorrhea. Therefore, young female patients should be monitored carefully by a doctor.

Other anticonvulsants used for bipolar disorder include carbamazepine (Tegretol), lamotrigine (Lamictal), gabapentin (Neurontin) and topiramate (Topamax). The evidence for anticonvulsant effectiveness is stronger for acute mania than for long-term maintenance of bipolar disorder. Some studies suggest particular efficacy of lamotrigine in bipolar depression. At present, the lack of formal FDA approval of anticonvulsants other than valproic acid for bipolar disorder may limit insurance coverage for these medications.

Most people who have bipolar disorder take more than one medication. Along with the mood stabilizer — lithium and/or an anticonvulsant — they may take a medication for accompanying agitation, anxiety, insomnia or depression. It is important to continue taking the mood stabilizer when taking an antidepressant because research has shown that treatment with an antidepressant alone increases the risk that the patient will switch to mania or hypomania, or develop rapid cycling. Sometimes, when a bipolar patient is not responsive to other medications, an atypical antipsychotic medication is prescribed. Finding the best possible medication, or combination of medications, is of utmost importance to the patient and requires close monitoring by a doctor and strict adherence to the recommended treatment regimen.