If a doctor has prescribed lithium for you or someone close to you, you may
wish to know more about the medication Is it safe? Will it cause discomfort?
Most importantly, will it work? Chances are you've been told hat lithium may
prevent future bouts of your illness. You can benefit from this remarkable
effect only if you continue to take the drug exactly as the doctor 
prescribes. You may have to take it for long periods of time, perhaps 
indefinitely. That means lithium is as important to you as insulin is to a
diabetic or other kinds of daily medications are to people with high blood
pressure. Like a diabetic or hypertensive person, you may question whether
you need to continue taking the medication day after day, especially if you
feel well. But lithium can save your life as surely as those other drugs
save theirs. This pamphlet will help you learn more about lithium.

Lithium: Mineral and Drug

Pure lithium, like sodium, calcium, or potassium, is a naturally occurring mineral. Lithium is found abundantly in certain rocks and the sea and in minute amounts in plant and animal tissues. Lithium also shows up in water, notably in the springs and spas where in earlier times people "took the waters," bathing in and drinking the lithium-rich water for its soothing effects. Whether lithium actually calmed 14th-century ladies and gentlemen has never been documented. What we do know is that, from time to time since antiquity, doctors have noticed that lithium can control over excitement in some of their patients. Today, lithium is administered to patients as a lithium salt, usually as lithium carbonate or lithium citrate, which is taken by mouth in capsule, tablet, or syrup form. Pharmaceutical companies often assign a "trade name" to their products. Examples of trade names for lithium are Cibalith, Eskalith, Lithane, and Lithobid. Some companies use only the chemical name, that is, lithium carbonate or lithium citrate. Modern physicians rely on these various forms of lithium to treat serious mental illness. Properly administered, it is one of the most powerful medications available for mood disorders. 

What Are Mood Disorders?

Patients with mood disorders, also called affective disorders, suffer from depression. In contrast to "the blues" that we all go through, a depressive episode is a true illness, often referred to as clinical depression. Some patients also experience episodes of mania-intense excitement and mental disorganization that usually require immediate hospitalization. Although mania is popularly thought of as a state of excess euphoria, patients report that a depressive mood is as frequent as euphoria during a manic episode, and irritability is the most common symptom. According to the National Institute of Mental Health (NIMH)-the Federal agency that supports research nationwide on the causes, treatment, and prevention of mental illness-depression is one of the most common mental disorders. The latest NIMH surveys indicate that during the course of a year, 5 in every 100 Americans has an episode of clinical depression and another 1.2 percent has an episode of manic-depressive illness that might consist of mania, depression, or the combination of both. Unlike the ups and downs of everyday life, clinical depression envelops a person in a dark cloud of gloom and lethargy. Often, no cause can be found for the extreme sadness-no death or financial setback or ruined romance. Although such losses can trigger a depressive episode, the sadness and apathy of clinical depression are deeper and go on far longer than is usual when a person grieves a loss. Without treatment, depression can continue for years, but typically it will last from 4 to 12 months. During a depressive episode, thinking slows down, concentration and memory are impaired, decisions are difficult to make, eating and sleeping habits may become disrupted, and anxiety-sometimes in the form of panic attacks-can add to the individual's overall misery. People with depression usually feel that they have lost their value, that they are no good to anyone. When they also lose all hope of regaining their sense of self-worth, some may come to feel that suicide is the only option left to them. In fact, about one in five individuals with depression will attempt suicide. In some people, the "lows" of depression more or less alternate with the "highs" of mania. In its early stages, mania may feel much like waking on a sunny day full of energy, good will, and high spirits, with a head full of ideas. These periods of hypomania that is, something less than full-blown mania pleasurable as they are, can quickly progress to true mania. By the time a person has reached that stage, thoughts are racing so fast that it is impossible to carry through any one idea. Good judgment vanishes. Manic individuals may spend the family into bankruptcy, engage m multiple sexual liaisons, pick fights with the boss, start grandiose projects that have no chance of success, grow angry too quickly, drink far too much, and generally convey the impression that they are not bound by earthly limitations on time, the need for sleep, or consideration of others. As this strange mix of symptoms implies, depression and mania are part of the same illness, bipolar disorder, which is also called manic-depressive illness. The mix of depression and mania varies tremendously from one patient to the next, as does the timing of episodes and their duration. Some people may experience both depression and mania at the same time; these are the mixed states that doctors sometimes refer to. Some patients cycle rapidly from one state to the other, sometimes within the course of a day. Some people have episodes of clinical depression alternating with hypomania that never progresses to mania; this form is usually called bipolar-II illness. Severe depression that occurs without mania is usually referred to as unipolar depression, clinical depression, major depression or, sometimes, the classic term, melancholia. Left untreated, manic-depressive illness nearly always recurs. A first episode in the late teens or early twenties, the typical age of onset, tends to be followed by episodes that get closer and closer and then settle into a somewhat regular pattern of recurrences. Unipolar depression may also recur. In either case, these illnesses rob the patient of years of life. Much of that suffering can be avoided with lithium and other treatments. Mania and clinical depressions, especially the forms that tend to recur, clearly reelect some malfunction in the brain. Scientists have been able to use new brain imaging technologies to picture such differences. In addition, research on the biochemical aspects of these illnesses suggests that faulty regulation of neurotransmitter, the chemical messengers that help nerve cells to communicate, is involved in depression and mania. Also important are various hormones, especially those that regulate the body's response to stress. Scientists have learned enough about these processes to realize that, so far, they know only part of the story. They have also developed a profound respect for the complexity of the human brain. One surprisingly complex aspect of the brain is its capacity to change, to be influenced by the person's experience-losing a parent at a critical age in childhood, for example, or feeling under great pressure at home or work from time to time. Such experiences can produce physical changes in the central nervous system and affect the brain's capacity to regulate mood. In some people, these adverse experiences may trigger the changes that end in clinical illness. 

The Development of Lithium Treatment

John Cade, an Australian physician, introduced lithium into psychiatry in 1949 when he reported that lithium carbonate was an effective treatment for manic excitement. Unfortunately, Dr. Cade's discovery coincided with reports of several deaths from the unrestricted use of lithium chloride as a salt substitute for cardiac patients. Four patients died, and several developed toxic reactions. It was not known at that time that lithium can accumulate to dangerous levels in the body or that lithium has to be used with special caution in patients with cardiac disorders. As a result of these experiences, lithium was virtually neglected in this country until the early 1960s. Research by European psychiatrists, especially Dr. Mogens Schou in Denmark, hastened acceptance of lithium in the United States. Renewed interest in the compound led to numerous clinical trials, including pivotal studies conducted by NIMH. These studies showed how lithium could be used safely and effectively to treat psychiatric disorders. In addition, research-both in animals and humans-showed that lithium influences several functions in the body, including the distribution of sodium and potassium, which regulate impulses along the nerve cells. Lithium can affect the activity of neurotransmitter and biological systems because it alters the way in which a variety of messages are transmitted after they reach their target. Although scientists have many promising leads, they have yet to explain the biochemical actions of depression. In 1970, the U.S. Food and Drug Administration (FDA) approved lithium as a treatment for mania. Four years later, the FDA also approved the use of lithium as a preventive, or prophylactic, treatment for manic-depressive illness.

Lithium's Uses

Psychiatrists use lithium in two ways: to treat episodes of mania and depression and to prevent their recurrence. Lithium can often subdue symptoms when a patient is in the midst of a manic episode, and it may also ameliorate the symptoms of a depressive episode. The single most important use for lithium, though, is in preventing new episodes of mania and depression. Lithium is also being used experimentally to treat other disorders. 

Manic and Depressive Episodes

Lithium is highly effective in treating acute episodes of mania, especially when symptoms are mild. Patients going through severe manic episodes need to be calmed as quickly as possible, however, and lithium may take 1 to 3 weeks to achieve its full effect. Therefore, physicians most often treat very disturbed patients by first combining lithium with a different type of drug, a tranquilizer, such as haloperidol or chlorpromazine. When lithium has had a chance to act, the tranquilizer may be gradually withdrawn. Lithium can normalize the manic disorder without causing the drugged feeling that often occurs with tranquilizers. Also, tranquilizers may produce troublesome side effects that limit their usefulness as a long-term treatment. Lithium is also effective in treating depressive episodes in some patients with manic-depressive illness. For these patients, some doctors prefer to treat mild to moderate depressive episodes with lithium alone because of the possibility that conventional anti-depressant drugs such as imipramine may trigger a hypomanic or manic attack. If the depression is severe, treatment is usually begun with a conventional antidepressant in combination with lithium. That same combination is sometimes used in unipolar depressions that do not respond to anti- depressant medications alone. 

Lithium's Role in Preventing Manic and Depressive Episodes

As noted, lithium's greatest value is in preventing or reducing the occurrence of future episodes of bipolar disorder. The effectiveness of this lithium prophylaxis or lithium prophylactic treatment has been demonstrated in more than two decades of careful research. In related research, several major studies indicate that lithium can decrease the frequency or severity of new depressive episodes in recurrent unipolar disorder. This suggests that lithium may also have prophylactic value in treating this mood disorder. Conventional antidepressants also have been shown to be effective prophylactic treatment for recurrent unipolar depression. In prophylactic treatment, lithium is administered after a manic or depressive episode to prevent or dampen future attacks. Some patients respond quickly and have no further episodes. Others respond more slowly and continue to have moderate mood swings even months after therapy is started. These highs or lows usually become progressively less severe with continued lithium treatment; often they disappear. With other patients, lithium may not prevent all future manic and depressive episodes, but may reduce or lessen their severity so that the individual can continue to lead a productive life. There are patients who are not helped at all by lithium. About one in ten patients with bipolar disorder who takes lithium does not respond to the medication, but continues to have manic-depressive episodes at the same frequency and severity as before. Doctors cannot predict with certainty how lithium will work in any individual case. This can be determined only by actual use of the medication. When deciding whether a patient should start lithium prophylactic therapy, a psychiatrist or other physician considers the likelihood of a new episode in the near future; the impact that the episode might have on the patient, family, and job; the patient's willingness to commit himself or herself to a long-term treatment program; and the presence of medical conditions that may rule out lithium treatment. Usually, a doctor prescribes lithium prophylactic therapy only after a patient has had two or three well-defined episodes requiring treatment. Patients who have had only a single attack, mild attacks, or a long interval between episodes-for example, over 5 years-usually do not receive prophylactic treatment unless the second episode would be life threatening or highly disruptive to the patient's career or family relations. Such rules, though, serve as only broad guidelines. Patients must act as the doctor's partner in weighing the circumstances and making the decision. Each patient should understand the reasons for lithium prophylaxis is as well as the benefits and risks and be an informed participant in the treatment program. When lithium fails or when a patient has another medical condition that precludes its use, the doctor may consider an alternative prophylactic drug treatment. First, however, he or she will reevaluate why lithium failed: Was dosage adequate? Did the patient take the medication as prescribed? Does the patient have a problem with thyroid function? Many patients with mood disorders have malfunctioning thyroid glands, a problem that can be successfully treated with a thyroid hormone or related preparations without withdrawing lithium. For manic-depressive patients, the anticonvulsant drugs carbamazepine (trade name Tegretol) and valproate (trade name Depakote) seem to be the best alternatives to lithium. Sometimes the anticonvulsant drugs are given alone, sometimes in combination with lithium, to prevent or dampen future episodes. Patients with unipolar disorder who fail on lithium often are given an antidepressant drug alone or in combination with lithium. A severe episode may be treated with electroconvulsive therapy. Information on alternatives to lithium treatment can be found in the literature listed at the end of the pamphlet.

Other Disorders

Lithium may also be useful for treating other mental illnesses. Research psychiatrists have evaluated lithium as a treatment for a variety of psychiatric disorders, including schizophrenia, schizoaffective disorder, alcoholism, premenstrual depression, and periodic aggressive and explosive behavior. Lithium appears to produce the best responses in patients who have mood swings, a tendency to have intermittent bouts of illness, or a family history of mood disorder. 

Lithium's Side Effects

Most patients do not experience serious side effects when they begin lithium therapy. Initially, the patient may have slight nausea, stomach cramps, diarrhea, thirstiness, muscle weakness, and feelings of being somewhat tired, dazed, or sleepy. A mild hand tremor may emerge as the dose is increased. These effects are normally minimal and usually subside after several days of treatment. But some of the initial side effects may carry over into long-term therapy and others may emerge. Some patients continue to have a slight hand tremor. Many drink more fluids than usual without always being aware of it-and urinate more frequently, while still others may gain weight. Weight gain often can be controlled with proper diet. Crash diets should be avoided, however, since they may adversely affect lithium levels. Also, to avoid excessive weight gain, excessive amounts of drinks with high sugar content should be avoided. In patients who have low amounts of thyroid hormone, enlargement of the thyroid gland may develop, but this condition is generally not serious if monitored closely by a physician. It can be successfully treated with supplementary thyroid medication without withdrawing lithium. Because of physiological changes in kidneys observed in some lithium-treated patients, any past or current kidney disorder or changes in frequency of urination should be reported to the physician. Long-term lithium therapy can also worsen certain skin conditions, especially acne and psoriasis, and may produce edema, or swelling, which is due to accumulation of water in tissues. Lithium must be taken with care, with attention to taking the proper dose, having regular blood tests, and reporting changes in diet, exercise, and the occurrence of illness. Toxic levels of lithium in the blood can cause vomiting, severe diarrhea, extreme thirst, weight loss, muscle twitching, abnormal muscle movement, slurred speech, blurred vision, dizziness, confusion, stupor, or pulse irregularities. Sudden physical or mental changes should be reported to the doctor immediately. These problems can almost always be avoided when the doctor's instructions are followed carefully. 

Periodic Blood Tests

The amount of lithium needed to treat or prevent manic and depressive symptoms effectively differs greatly from one patient to another. The doctor determines how much lithium a patient needs by taking a sample of blood from time to time. The blood is analyzed to determine how much lithium is present. Testing for the lithium blood level is a vital part of treatment with lithium. It aids the doctor in selecting and maintaining the most effective dose. Just as important, lithium blood levels assure the doctor that a patient is not taking a toxic dose-that is, a poisonous dose. Lithium is an unusual drug because the amount needed to be effective is only slightly less than the amount that is toxic. For that reason, patients must be very careful not to take more lithium than prescribed. Lithium levels in the blood can change even when the patient takes the same dose every day: The concentration of lithium can increase when a person becomes ill with another medical condition, especially influenza or other illnesses that result in fever or changes in diet and loss of body fluids. Surgery, strenuous exercise, and crash diets are other circumstances that can lead to dangerously increased lithium levels in the blood. The doctor should be informed of illness or changes in eating habits, and a regular blood testing schedule should be set up and followed rigorously. If a patient stops taking lithium for only one day, the blood level of the drug falls to half that needed for effective therapy. A forgotten dose should not, however, be taken with the regular dose the next day, because it could raise the lithium level too much. Furthermore, the lower lithium level that results from missing one dose is unlikely to jeopardize therapeutic response. Because the blood level of lithium rises rapidly for a few hours after swallowing a lithium pill and then slowly levels off, having a blood test right after taking the drug can mislead the doctor into thinking that the dose is too high. To gauge the average blood level accurately, it is important to have blood drawn about 12 hours after the last dose of lithium. Otherwise, the results will be misleading and possibly dangerous. Most patients take their nighttime dose of lithium and then come to the doctor's office the next morning to have a blood test before taking their first dose for the day. Some patients are able to take their full daily dose at bedtime and don't have to worry about the morning dose when getting a blood level.

Precautions in Taking Lithium

Lithium is excreted from the body almost entirely by the kidneys. If, for some reason, the kidneys are unable to get rid of the proper amount of lithium, the drug may accumulate to dangerous levels in the body. The excretion of Lithium in the kidneys is closely linked to that of sodium. The less sodium, or salt, in the body, the less Lithium is excreted, and the greater chance of Lithium buildup to toxic levels. Diuretics cause the kidneys to excrete sodium; as a result, Lithium levels rise. The reason that many illnesses can increase lithium levels is that increased sweating, fever, a low salt diet, vomiting, and diarrhea all result in less sodium present in the body, thus producing higher levels. Lithium should not be taken by patients with severely impaired kidney function. Patients with heart disease and others who have a significant change in sodium in their diet or periodic episodes of heavy sweating should be especially careful to have their lithium blood levels monitored regularly. For women in the fertile age range, the possibility of harmful effects on the unborn child may pose problems for continued use of lithium. Children of mothers who received lithium during the first 3 months of pregnancy have been reported in some, but not all, studies to have a slightly increased frequency of malformations of the heart and blood vessels. Even though this risk is low and uncertain, it is strongly recommended that women discontinue Lithium during the first 3 months of pregnancy. The decision to stop the medication, however, must be weighed against the possible consequences of an untreated manic or depressive attack, which may result in injury, physiological stress, dehydration and malnutrition, sleep deprivation, or possibly even suicide. Because of the risk of postpartum depression or mania, lithium is sometimes restarted during the final weeks before birth is expected. Women should not breast feed when they are taking lithium, except in rare circumstances when the potential benefits to the mother outweigh possible hazards to the child. 

Taking Lithium: How Long?

When fully effective, Lithium can control manic-depressive illness for the rest of a person's life. But it is not a cure. Like antihypertensive medications for controlling high blood pressure, lithium should not be discontinued without consulting the physician. Unfortunately, some patients stop taking their lithium when they find that it diminishes the wonderful sense of well-being they felt when hypomanic; most resume taking their medication when disabling manic episodes return. Other patients discontinue Lithium because they feel they no longer need it. Such reasoning is perfectly understandable. When a person remains well week after week, there is a tendency to forget to take lithium or to deliberately stop taking the medication, believing that the illness has been cured. Lithium's effects, however, last only when patients regularly take the medication. If patients stop taking Lithium-no matter if they've been taking it for 5 weeks or 5 years-the hances of having another manic or depressive attack increase. In fact, patients who stop taking the medication are just as likely as patients who have never been treated to fall back into a manic or depressive episode. This does not mean, though, that all patients must take lithium for a lifetime. After a long period of treatment without a recurrence of mania or depression, the doctor and patient may consider withdrawal of medication under dose supervision. That decision will depend upon several factors, including the impact that a subsequent episode may have on the patient's marriage or other significant relationships, career, and general functioning; the likelihood that an emerging recurrence will be detected early enough to prevent a full-blown attack; and the patient's tolerance of lithium. 

A Checklist for Patients Taking Lithium



1. Take the medication on a regular basis as a prescribed by the doctor. Ask the doctor for instructions on what to do if one or more doses are missed. Unless the doctor advises otherwise, do not catch up on the missed dose by doubling the next dose. This may produce a dangerously high blood level of lithium.
2. Obtain regular blood tests for lithium levels.
3. Have the doctor take blood tests for lithium levels 12 hours after the last dose. Inform the doctor if it has been less than 11 hours or more than 13 hours since the last dose.
4. Inform the doctor if other medications are being taken, since they can change lithium levels.
5. Notify the doctor whenever there is a significant change in weight or diet. It is especially important to tell the doctor if you plan to begin a rapid weight-loss diet, since lithium levels in the body may be drastically affected.
6. Advise the doctor about any changes in frequency of urination, loss of fluids through diarrhea, vomiting, excessive sweating, or physical illness, particularly if there is a fever, because adjustment of dosage or further testing may be required.
7. If planning to become pregnant, advise the doctor
8. If another doctor is being seen or an operation is planned, be sure to inform that doctor that you are taking lithium.
9. because it may take time for mood swings to be completely controlled by lithium, try not to get discouraged. Continue taking the medicine as prescribed until advised otherwise by the doctor. However, be sure to notify the doctor of the recurrences in mania or depression because it may be necessary to increase the dose or receive additional medication for a time. Psychotherapy can help you recognize manic or depressive episodes early in their course, as well as help you to express and understand your feelings about having manic-depressive illness.
10. Ask the doctor any questions about the treatment program or any procedures that you do not understand. A well-informed patient and family are important factors contributing to successful treatment outcome. Also. if your psycho-therapist is someone other than the doctors prescribing the medication, it is important for the two professional to exchange information about your progress and problems as needed. 

Information Resources

Suggested Reading

• Bohn, J., and Jefferson, J. Lithium and Manic Depression A Guide. Rev. ed. Madison, WI: Lithium Information Center, University of Wisconsin, 1990.
• Fieve, R. Moodswing: The Third Revolution in Psychiatry. Rev. ed. New York: William Morrow and Company, 1989.
• Gold, M. The Good News About Depression. New York: Villard Books, 1987.
• Goodwin, F.K., and Jamison, K.R. Manic-Depressive illness. New York and Oxford: Oxford University Press, 1990.
• Jefferson, J., and Greist, J. Valproate and Manic Depression: A Guide. Madison, WI: Lithium Information Center, University of Wisconsin, 1991.
• Jefferson, J.; Greist, J.; Ackerman, D.; and Carroll, J. Lithium Encyclopedia for Clinical Practice. Rev. ed. Washington, DC: American Psychiatric Press, Inc., 1987.
• Johnson, F.N., ed. handbook of Lithium Therapy. Lancaster, England: MTP Press Ltd., and Baltimore, MD: University Park Press, 1980.
• Johnson, F.N. Depression and Mania: Modern Lithium Therapy. Oxford: IRL Press, 1987.
• Medenwald, J.; Greist, J.; and Jefferson, J. Carbamazepine and Manic Depression: A Guide. Rev. ed. Madison, WI: Lithium Information Center, University of Wisconsin, 1990.
• Post, R., and Uhde, T. Refractory manias and alternatives to lithium treatment. In: Georgotis, A., and Cancro, R., eds. Depression and Mania. New York: Elsevier, 1988.
• Prien, R.F., and Potter, W.Z. National Institute of Mental Health workshop report on treatment of bipolar disorder. psychopharmacology Bulletin 26(4):409-427, 1990.
• Schou, M. Lithium treatment of manic-depressive illness: Past, present, and perspectives. Journal of the American Medical Association 259:1834 1836, 1988.
• Schou, M. Lithium Treatment of Manic-depressive illness: A Practical Guide. Rev. ed. New York and Basel: Karger, 1989. 


For More Information on Mood Disorders and Lithium
Dean Foundation
8000 Excelsior Drive,
Suite 203
Madison, WI 53717-1914
(608) 836-8070
-------------------------- All material in this pamphlet is free of copyright restrictions and may be copied, reproduced, or duplicated without permission from the Institute; citation of the source is appreciated. This booklet was written by Robert F. Prien, Ph.D., and William Z. Potter, M.D., Ph.D., psychopharmacology and manic-depressive illness experts, National Institute of Mental Health. Editors were Bette Runck and Lynn J. Cave, NIMH.