Mood Stabilizers

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Aetna Intelihealth InteliHealth Aetna Intelihealth Aetna Intelihealth
 
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Harvard Medical School
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Mood Stabilizers

Depression
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What Kind Of Treatment Is Available?
Mood Stabilizers
Mood Stabilizers
htmMoodStabilizers
Mood stabilizers are well known treatments for bipolar illness, but they also are used in the treatment of depression.
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InteliHealth
2011-10-06
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InteliHealth/Harvard Medical Content
2014-10-06

Reviewed by the Faculty of Harvard Medical School

Mood Stabilizers
 
The term "mood stabilizer" usually refers to a drug that treats the up (manic) and down (depressed) mood swings that occur in bipolar disorder. This disorder used to be called manic-depressive illness.
 
Mood stabilizers are sometimes used to treat depression, even if the person has never been manic. When used to treat depression, mood stabilizers are commonly combined with antidepressants. This either enhances the effect of the mood stabilizer or protects against a manic episode. Sometimes mood stabilizers are used alone to treat depression.
 
The best-known drug in this category is lithium. Other drugs that are established mood stabilizers include valproate, carbamazepine and lamotrigine.

 

Lithium
 
Lithium is one of the oldest mental-health drugs still in use. It has been studied more extensively than any other mood stabilizer since its inception in the 1960s. It is the best-known drug in this category and it remains the best treatment and prevention for episodes of mania and depression.
Lithium is primarily used to treat bipolar disorder. It may also be a good choice to treat and prevent the depression associated with bipolar disorder. Lithium can reduce some of the smaller ups and downs of mood that occur between major depressive episodes. In people with bipolar disorder, lithium appears to reduce the risk of suicide. Sometimes lithium is used to boost a person's response to an antidepressant.
Doses
 
A typical starting dose of lithium is 300 milligrams, taken two or three times per day. Your doctor may gradually increase your dose depending on how you respond and whether you have side effects. (Later, once the proper dose is established, you may need only a single daily dose.)
 
If you experience side effects, try taking your lithium with meals or ask your doctor if you can switch to a slow-release form. (Slow-release pills must be swallowed whole; don't crush or chew them.)
 
Lithium levels. Because it takes several days for lithium levels in your blood to even out, your doctor will probably test your blood about five days after you start taking lithium or after you increase your dose. Higher levels are linked to fewer relapses, but lower levels bring fewer side effects. You and your doctor should discuss what approach works best for you.
 
Side Effects
 
As many as three-quarters of people taking lithium experience some unwanted side effects. Sometimes changing the dose eliminates the side effect. Side effects are usually not dangerous, but they can be uncomfortable, and may include:
  • Tremor, muscle weakness
  • Nausea, loss of appetite
  • Weight gain
  • Trouble concentrating, a feeling of mental dullness
  • Acne
  • Slurred speech
  • Vision problems
  • Increased urination, unusual thirst
  • Muscle stiffness
  • Trouble breathing (especially during physical work or exercise)
  • Dizziness
  • Eye pain, headache
  • Signs of an underactive thyroid — dry skin, hair loss, sensitivity to cold, neck swelling (goiter), depression
Your doctor may detect other side effects, although it is unlikely that the side effects listed below will cause you any discomfort or danger:
  • Your white-blood-cell count may go up. (Your doctor will note this on the blood tests you undergo as part of lithium treatment.) 
  • If you underwent an electrocardiogram (EKG or ECG) before treatment to assess your normal heart rhythm, a second EKG during treatment may report different readings. In most cases, these changes should be of no concern. 
  • There may be microscopic changes in your kidney cells, although damage to kidney function is rare. (Your doctor will likely test your kidney function before and during treatment.)
  • Lithium may suppress your thyroid function. If this occurs, you may need to take thyroid hormone pills.
If you notice these or any changes after you start taking lithium, talk to your doctor.
 
Warnings
 
At standard treatment doses, lithium is safe. However, it quickly becomes dangerous if the level in your blood rises above a therapeutic level. There is a relatively small difference between a treatment dose and a toxic dose. That's why you need to undergo blood tests to monitor the level of lithium in your blood. You'll be tested frequently at the beginning of treatment, then taper off to being tested every six months once a stable dose is found. Have your blood drawn in the morning, before you take your first dose of lithium for the day.
 
Early signs of lithium toxicity are a severe tremor, nausea and diarrhea. Blurry vision, dizziness and confusion may occur. High doses of lithium may cause seizures or a coma. A disturbed or dangerous heart rhythm can occur, as can brain damage. In some cases, lithium toxicity can be lethal. If you miss a dose, do not double up on your dose.
 
Moderate or severe toxicity is a medical emergency. Stop taking you lithium immediately. You may need to be hospitalized to make sure your fluid and salt balance is maintained. Some people need to have any remaining lithium removed from their stomachs through a tube. In severe cases, dialysis is needed to reduce the lithium level quickly.
 
Lithium toxicity may result from a high dose of lithium, but other things can cause it, too:
  • Dehydration — Drink plenty of fluid, especially during hot weather and while exercising. Be extra careful if you do things that cause you to sweat a lot, such as exercising or using a sauna.
     
  • Low-salt diet — If you have too little salt in your body, your kidneys hold onto lithium, leading to increased levels. Use a normal amount of salt in your diet (unless your doctor tells you otherwise). 
  • Diuretics ("water pills") — Used to treat high blood pressure, water pills often run down the body's supply of sodium salt. If you take water pills and lithium, your kidneys will hold onto the lithium salt, causing lithium levels to rise.
     
  • Changes in kidney function — If the kidneys slow down (which occurs with age), they take longer to eliminate lithium from your system, causing levels to rise.
     
  • Antipsychotic drugs — These can change the concentration of lithium in your blood.
     
  • Anti-inflammatory drugs (such as Motrin) — These drugs can change the concentration of lithium in your blood. 
  • Drugs that contain calcium, potassium or iodine — These can change the concentration of lithium in your blood.
  • Psoriasis — Lithium can worsen psoriasis, a skin disorder of scaling and inflammation.
 
Pregnancy and breast-feeding. Lithium can harm a developing fetus, which is why it is usually not prescribed for pregnant women. It is often wise to get a pregnancy test before you start taking lithium. Lithium will pass into breast milk, which means a breast-fed baby will absorb some, causing unwanted effects. Discuss the pros and cons of breast-feeding with your doctor.

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Valproate
 
Initially used to treat seizures, valproate (Depakote) is an effective treatment for the mania of bipolar disorder. It may be a particularly good choice for people who have mixed mania, in which there is a blend of mania and depression, or for people who tend to cycle quickly between mania and depression.
 
Valproate is generally not used to treat unipolar depression. Valproate is frequently used with another mood stabilizer (lithium or carbamazepine), an antidepressant or other drugs.
Types And Doses
 
Typically, valproate is started at a low dose (for example, 250 milligrams) taken twice or three times per day. This low dose helps you avoid stomach upset and feeling sedated. The dose is then increased every few days by 250 or 500 milligrams. During this time, your doctor monitors how you respond and asks about side effects. He or she will check the level of valproate in your blood. The dose may be modified depending on how much you weigh or if you take other drugs that interact with valproate. Therapeutic doses can be about 2,500 milligrams a day.
When someone needs immediate treatment, for example, during severe mania, a "loading dose" may be used. This is calculated as weight (in kilograms) multiplied by 20. For example, a 176-pound (80-kilogram) man would get a dose of 1,600 milligrams
per day.
 
Side Effects
 
Side effects are usually not dangerous, but they can be uncomfortable. Some are more common as you start treatment, but then go away:
  • Feeling tired (sedation)
  • Stomach distress (nausea, vomiting, diarrhea)
  • Increased appetite, weight gain
  • Tremor
  • Stomach cramps
  • Restlessness or irritability
  • Double vision
  • Lowered blood-cell counts (can affect any of the blood-cell types)
  • Unusual bleeding or bruising
  • Constipation
  • Dizziness
  • Skin rash
  • Hair loss (usually a short-lived symptom)
If you notice these or any other changes, talk to your doctor.
 
Warnings
 
Your doctor may periodically check your liver function and blood counts. Toxic reactions are uncommon, even with high doses or overdoses. (Although, if you miss a dose, do not double up on your dose.) Life-threatening reactions are rare, but can occur.
 
Valproate can cause liver toxicity, inflammation of the pancreas, suppression of blood counts and increased ammonia levels. Tell your doctor if you have any of these symptoms:
 
  • Fatigue, weakness, sluggishness, facial swelling, loss of appetite, vomiting — indicating possible liver toxicity
  • Abdominal pain, nausea, vomiting, loss of appetite — indicating possible inflammation of the pancreas
  • Bruising, bleeding, infection, low energy — indicating possible low blood count
  • Confusions, disorientation or difficulty thinking -- indicating possible high ammonia levels
 
People with liver disease or diseases of the blood are at greater risk.
 
Surgery. If you need surgery or dental work, let your doctor know you take valproate. It may increase the amount of time it takes for your blood to clot.
 
Pregnancy and breast-feeding. Valproate can cause birth defects, especially during the first three months of pregnancy. Discuss with your doctor the risks and benefits of taking this drug during pregnancy or when nursing. Valproate can pass into breast milk, which means a breast-fed baby absorbs the drug. The effects on a breast-fed baby are unknown.

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Carbamazepine
 
Carbamazepine (Tegretol) is similar to valproate in that it was developed to treat seizures. It is also used to treat the mania of bipolar disorder, although it is not as effective as lithium or valproate. Carbamazepine is sometimes helpful when lithium or valproate have not worked. Carbamazepine is not usually used alone. It is most often combined with other mood stabilizers, antidepressants and/or antipsychotic drugs.
Types And Doses
 
The starting dose of carbamazepine is generally 200 to 600 milligrams per day, given in three or four doses. The dose is determined by measuring your response and side effects and by checking the level of the drug in your blood. It can take several weeks or more to establish a stable, therapeutic dose for this drug.
 
Your doctor will periodically order blood tests to check your blood level of the drug, your complete blood counts and liver function. If your results stabilize over time, the need for testing becomes less frequent.
 
Side Effects
 
Side effects usually are not dangerous, but they can be uncomfortable. Some are more common as you start treatment, but then go away:
  • Unsteadiness or mild dizziness
  • Mild drowsiness or lightheadedness
  • Nausea or vomiting
  • Blurry vision
  • Joint and muscle aches
  • Constipation or diarrhea, loss of appetite, stomach discomfort
  • Dry mouth
  • Headache
  • Skin rash, hives or itching; increased sensitivity to sunlight
  • Increased sweating
  • Hair loss
  • Confusion or agitation
  • Low salt concentrations in the blood, usually in the elderly
If you notice these or any other changes, talk to your doctor.
 
Warnings
 
Life-threatening reactions are rare but can occur. Carbamazepine can cause liver toxicity, inflammation of the pancreas, and suppression of blood counts. It can also cause a rare, severe inflammation of the skin. Tell your doctor if you have any of these symptoms:
  • Fatigue, weakness, sluggishness, facial swelling, loss of appetite, vomiting — indicating possible liver toxicity
  • Abdominal pain, nausea, vomiting, loss of appetite — indicating possible inflammation of the pancreas
  • Bruising, bleeding, infection, low energy — indicating possible low blood counts
  • Reddish or bluish skin; swelling, puffiness or tenderness; fever, aches and pains; blistering or peeling — indicating possible skin inflammation
These severe reactions usually occur in the first three to six months of treatment. People with liver disease or diseases of the blood are at greater risk.
 
An overdose of carbamazepine can be fatal. Signs of toxicity are dizziness, poor balance, sedation and double vision. People can also become very irritable or lapse into a coma. There may be trouble breathing, a rapid or irregular heartbeat or a drop in blood pressure.
 
Drug interactions. Carbamazepine can interact with many other drugs. It can cause the liver to break down some drugs more efficiently, meaning it decreases levels of other drugs in your blood, including antidepressants, antipsychotics, antianxiety drugs and other antiseizure drugs. It can also change levels of birth-control pills and thyroid-hormone pills.
 
Other commonly prescribed drugs can drive up carbamazepine levels, including erythromycin, some blood-pressure drugs and antidepressants known as selective serotonin reuptake inhibitors, which include Prozac and others.
 
Pregnancy and breast-feeding. There are reports of harmful effects to a fetus if carbamazepine is taken during pregnancy. Discuss with your doctor the risks and benefits of taking this drug while pregnant or nursing. Carbamazepine passes into breast milk, which means a breast-fed baby will absorb the drug. It may affect a baby's growth.

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Lamotrigine
 
Because the antiseizure drugs valproate and carbamazepine have worked for bipolar disorder, researchers are studying other antiseizure drugs to see if they will work on bipolar disorder, too. Of the newer antiseizure drugs, lamotrigine (Lamictal) is so far the most promising, particularly for treating and preventing episodes of depression. (Lamotrigine does not appear to work on mania.)
 
Doses
 
Lamotrigine's dose is adjusted carefully to reduce the risk of a major side effect (see Warning below). The guidelines for use are to start with a low dose and increase slowly: 25 milligrams per day for 2 weeks, then increasing the daily dose to 50 milligrams. Once at a 50-milligram dose, the dose can be increased in 50-milligram increments every 2 weeks. The usual therapeutic dose is between 200 and 400 milligrams per day.
 
Side Effects
 
Side effects usually are not dangerous, but can be uncomfortable. Most common are:
  • Headache
  • Dizziness
  • Nausea or vomiting
  • Blurred vision
  • Unsteadiness while walking
  • Runny nose
  • Irritability, anxiety or trouble concentrating
  • Feeling too sleepy or having trouble sleeping
Some side effects improve once your body becomes accustomed to the medication.
 
Warning: Stevens-Johnson Syndrome
 
The major drawback of lamotrigine is the risk of Stevens-Johnson syndrome. While rare, this potentially fatal allergic reaction involves the skin and mucous membranes. One of the first signs is a rash, so report any rashes to your doctor right away. In most cases, you should stop taking the drug until your doctor has a chance to evaluate your situation. If you experience other symptoms along with the rash — discomfort around the eyes and mouth, urinary symptoms, fever or swollen glands — it may be a medical emergency. Get evaluated immediately.
 

Except for this major risk, lamotrigine appears to be well tolerated. It doesn't seem to cause much sleepiness, fatigue, intellectual impairment, sexual problems or weight gain. The most common side effect is headache, and that often goes away after a stable dose is reached.

Drug interactions. The blood level of lamotrigine may change if you take other drugs at the same time. Valproate, for example, pushes the blood level up and carbamazepine pushes it down. So your doctor needs to move your lamotrigine dose down or up to compensate.
 
Pregnancy and breast-feeding. There is little known about using lamotrigine during pregnancy. Before taking lamotrigine, a woman should tell her doctor whether she is pregnant or may become pregnant. Lamotrigine passes into breast milk, though the effect on nursing babies is not known. Discuss with your doctor what approach works best for you as you care for yourself and for your baby.

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Last updated October 09, 2014


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