Feeling Good: The New Mood Therapy

by Burns, David D.

  • Recurrent manic and depressive mood swings in individuals with bipolar manic-depressive illness. Lithium has significant preventative effects, so that the likelihood of future manic episodes is reduced.

  • Single episodes of depression. Lithium is sometimes added in smaller doses to an antidepressant drug that is not working in order to try to improve its effectiveness. I will describe this and other augmentation strategies later in the chapter.

  • Recurrent episodes of depression in patients without manic mood swings. Lithium maintenance may help to prevent recurrences of depression following recovery. Some studies indicate that the preventative effects of long-term lithium treatment may be similar to the effects of long-term treatment with an antidepressant such as imipramine. However, this preventative effect on depression may not work for all patients. Lithium is probably more likely to prevent depressions in patients with a strong family history of bipolar (manic-depressive) illness.

  • Individuals with episodic anger and irritability or outbursts of violent rage.

  • Individuals with schizophrenia. Lithium can be combined with an antipsychotic medication, and the combination may be more effective than the antipsychotic medication alone. The improvement seems to occur in schizophrenic patients who also experience mania or depression and in schizophrenic patients without any symptoms of mania or depression.

  You should keep in mind that in all of these conditions, lithium is sometimes helpful but rarely ever curative. Like most medications, it is a valuable tool but not a panacea.

  As noted above, manic-depressive illness is sometimes also called bipolar illness. “Bipolar” simply means “two poles.” Patients with bipolar illness experience uncontrollable euphoric mood swings that often alternate with severe depressions. The manic phase is characterized by an extremely ecstatic, euphoric mood, inappropriate degrees of self-confidence and grandiosity, constant talking, nonstop hyperactivity, increased sexual activity, a decreased need for sleep, heightened irritability and aggressiveness, and self-destructive impulsive behavior such as reckless spending binges. This extraordinary disease usually develops into a chronic pattern of uncontrollable highs and lows that can come on unexpectedly throughout your life, so your physician may recommend that you continue to take lithium (or another mood stabilizing drug) for the rest of your life.

  If you have experienced abnormal mood elevations along with your depression, your physician will almost definitely prescribe lithium or another comparable mood-stabilizing drug. Some studies suggest that if you are depressed and have a definite family history of mania, you might benefit from lithium even if you have never been manic yourself. However, most physicians would first prescribe a standard antidepressant and observe you carefully. Although antidepressants do not usually cause euphoria or mania in people with depression, they can occasionally have this effect in individuals with bipolar manic-depressive illness. The mania can begin as quickly as twenty-four to forty-eight hours after starting the antidepressant.

  In my clinical practice, the development of a sudden and dangerous manic episode after starting an antidepressant has been quite rare, even in patients with bipolar illness. Nevertheless, if you have a personal or family history of mania, it is conceivable that you could experience this side effect. Be sure to tell your doctor about this so you can receive careful follow-up after starting an antidepressant. Your family, too, should be alerted to this possibility. Family members are often aware of the development of a manic episode before the patient realizes what is happening, and can alert the doctor that a problem has developed. This is because the distinction between normal happiness and the beginning of the mania may be unclear to the patient. Furthermore, mania feels so good at first that you may not recognize it as a dangerous side effect of the medication you are taking.

  Doses of Lithium. As you will see in Table 20–1, lithium comes in 300-mg dosages, and normally three to six pills per day in divided doses are required. Your physician will guide you. Initially, you may take the lithium three or four times per day. Once you are stabilized on lithium, you may be able to take half your total daily dose in the morning and half before you go to bed. This twice-a-day schedule will be more convenient.

  Sustained-release capsules containing 450 mg are also available. Because these drugs are released more slowly in the stomach and gastrointestinal tract, they may cause fewer side effects and they are more convenient because you don’t have to take them so often. However, their increased cost, as compared with generic lithium, may not justify taking them. Furthermore, many patients have reported that the side effects of the inexpensive, generic brands of lithium are no different from the more expensive slow-release brands.

  Like the other drugs used for treating mood disorders, lithium usually requires between two and three weeks to become effective. When taken for a prolonged period of time, its clinical effectiveness seems to increase. Thus, if you take it for a period of years, it may help you more and more.

  Unfortunately, there appears to be a group of individuals who do well on lithium, stop taking it, become symptomatic again, and then find that the lithium is less effective when they start taking it again. This is one reason why you should not stop taking lithium, or any other medication, without first consulting with your doctor.

  Lithium Blood Testing. Too much lithium in your blood can cause dangerous side effects. In contrast, if your blood level is too low, the drug will not help you. Because there is a narrow “window” of effectiveness of lithium, blood-level testing is required to make sure that your dose is neither too high nor too low. Initially, your doctor will order more frequent blood tests so that she or he can determine what the proper dose should be. Later on, when your dose and symptoms have stabilized, you will not need the blood tests nearly as frequently.

  If you are an outpatient and you are not experiencing severe mania, your doctor may order lithium blood tests once or twice a week for the first couple weeks, then once a month. Eventually, blood tests every three months may be sufficient.

  If you are being treated for a more severe episode of mania, more frequent blood tests will be required. This is because higher blood levels of lithium are usually needed to control the severe symptoms. In addition, your body tends to get rid of lithium more rapidly during an episode of mania, so larger doses may be needed to maintain the proper blood level. As noted above, during a manic episode your doctor will almost definitely want to combine lithium with more potent drugs for the first few weeks until your symptoms have subsided.

  Your blood must be drawn eight to twelve hours after your last lithium pill. The best time for a blood test is first thing in the morning. If you forget and take your lithium pill the morning of a blood test, don’t take the test! Try again another day. Otherwise, the results will be misleading to your doctor.

  Body size, kidney function, weather conditions, and other factors can influence your lithium dose requirement, so blood tests should be performed on a regular basis when you are on lithium maintenance. Your doctor will probably try to maintain your blood level at somewhere between 0.6 and 1.2 mg per cc, but this will vary with your symptom level. During an episode of acute mania, your doctor will probably want to keep your blood level closer to the top of the therapeutic range. Some doctors feel that levels as low as 0.4 to 0.6 mg per cc can be effective to help prevent an episode of depression or mania when you are feeling good.

  Patients with chronic irritability and anger may also respond to lithium at these lower blood levels, even if they don’t suffer from clear symptoms of manic-depressive illness. The advantage of these lower levels is that there are fewer side effects.

  Other Medical Tests. Prior to treatment, the doctor will evaluate your medical condition and order a series of blood tests and a urinalysis. These blood tests will usually include a complete blood count, tests of thyroid and kidney function, electrolytes, and blood sugar. Your thyroid functioning should be tested at six-month or yearly intervals while you are taking li
thium because some patients on lithium develop goiters (a swelling or lump on the thyroid gland) or underactive thyroid glands. Your kidney function must also be evaluated from time to time because of kidney abnormalities reported in some patients taking lithium. Your doctor may order an electrocardiogram (ECG) before you start taking the lithium, especially if you are over forty or if you have a history of heart problems. Your doctor will also need to know about any other drugs you may be taking, because some of them may cause elevations in your blood lithium level. These include certain diuretics as well as some anti-inflammatory drugs such as ibuprofen, naproxen, and indomethacin. You will learn below that some drugs can have the opposite effect of causing your lithium level to fall.

  Side Effects of Lithium. The side effects of lithium are listed in Table 20–12 on pages 624–625 and compared with the side effects of two other mood stabilizers I will discuss below. As you can see, lithium tends to have many side effects. Most of them are mildly uncomfortable but not serious.

  Starting with the effects on the muscles and nervous system first, you will see that lithium can cause a fine tremor of the hands and fingers in 30 percent to 50 percent of patients. This tremor will be present when your hands are resting and often worsens when you do something purposeful with your hands. For example, the tremor can make it more difficult to hold a cup of coffee or to write clearly. The severity of the tremor is related to the dose and may be more severe when lithium is prescribed along with one of the tricyclic antidepressants, which can also cause tremor.

  This tremor is one of the major reasons that some patients stop taking their lithium. An antitremor drug called propranolol (Inderal) can be given if the tremor is especially severe and troublesome, but it is my policy to avoid prescribing an additional drug if possible. A reduction in dose can also help.

  If your doctor does prescribe propranolol, the usual dose to reduce a lithium tremor is 20 to 160 mg per day, given in divided doses. It is best to start with small doses and increase gradually. The smallest effective dose is best. This is because propranolol can have other effects, including a slowing of the heart, a drop in blood pressure, weakness and fatigue, mental confusion, and upset stomach. Propranolol can also cause breathing difficulties and must not be given to patients with asthma. It is also contraindicated for patients with Raynaud’s disease. Metoprolol (25 to 50 mg) or nadolol (20 to 40 mg), drugs similar to propranolol, have also been used to treat lithium tremor.

  Lithium may cause tiredness and fatigue initially, but these effects will generally disappear with time. Some patients complain of mental slowing or forgetfulness, particularly younger individuals. The forgetfulness has been confirmed by memory testing. Other antidepressants that have anticholinergic properties, such as Elavil, can also cause forgetfulness. Complaints about these mental changes are very common and cause many patients to stop taking their lithium. Memory difficulties seem to be more pronounced at higher lithium blood levels, as might be expected, and often improve when the dose is reduced.

  Table 20–12. Side Effects of the Mood Stabilizersa

  aInformation in this table was obtained in part from the Manual of Clinical Psychopharmacology1 and Psychotropic Drugs Fast Fads.17 These excellent references are highly recommended.

  Along the same lines, some patients complain of substantial weakness and fatigue. These symptoms often indicate an excessive lithium level, and a dose reduction may be indicated. Extreme sleepiness with mental confusion, a loss of coordination, or slurred speech suggests a dangerously elevated lithium level. Discontinue the drug and seek immediate medical attention if such symptoms appear.

  Some patients express the fear that they may lose their creativity when they start taking lithium. This is especially of concern for artists and writers who have used their highs and lows as a source of painful inspiration for creative expression. Indeed, many well-known painters and poets through the centuries suffered from manic-depressive illness, and their moods were clearly reflected in their work. However, three quarters of patients on lithium report that it does not seem to reduce their creativity, and in some cases their creativity increases.1

  Turning next to the digestive system, lithium can cause an upset stomach or diarrhea that is most troublesome during the first few days of treatment. These side effects will usually disappear with time. It may help to take the lithium with food or to take it in three or four divided doses throughout the day, so that your stomach isn’t hit with a large dose all at once. It can also help to increase the dose of lithium more slowly. In rare cases lithium can cause vomiting as well as diarrhea, and your body may become dehydrated because of all the fluid loss. This can make your blood levels of lithium higher, and so the drug becomes more toxic. This, in turn, can cause more nausea and diarrhea, creating a vicious cycle. Medical attention may be needed to make sure you are adequately hydrated until the episode has passed.

  Unfortunately, many patients on lithium experience weight gain; this is another common reason patients stop taking the drug. Dr. Alan Schatzberg1 has suggested that this problem will be greater if you are already overweight. The weight gain results from the stimulation of your appetite. This is often very difficult to control. Obviously, if you exercise more and eat less, the weight gain can be prevented or reversed, but this is often much easier said than done! If the weight gain is excessive or troublesome, switching to an alternative mood stabilizer, such as carba-mazepine, may be helpful.

  Increased thirst and frequent urination can also occur when taking lithium. In some cases, patients develop intense thirst from urination that is so frequent and voluminous that the lithium must be stopped. This condition, known as nephrogenic diabetes insipidus (NDI), results from the effects of lithium on the kidneys. It is usually reversible when the lithium is stopped. In some cases, adding certain types of diuretics can also help. However, careful lithium monitoring must be performed, because these diuretics can cause increases in plasma lithium levels. Milder forms of increased urination probably occur in one half to three quarters of patients who take lithium.

  Lithium can cause a form of kidney damage called “interstitial nephritis.” This term simply means inflammation or irritation of the tissue. When first reported, psychiatrists were quite alarmed about this complication. Subsequent experience has indicated that although the problem may occur in 5 percent or more of patients who take lithium for many years, the degree of kidney impairment is usually mild. Your doctor will nevertheless want to monitor your kidney function periodically while you are on lithium. She or he will order two blood tests called the creatinine test and the blood urea nitrogen (BUN) test once or twice a year. These tests can be performed at the same time you are having your usual lithium blood test taken. If the tests indicate a change in kidney function, your doctor may request a consultation with a urologist and order a twenty-four hour creatinine clearance test. This is a more accurate test of kidney function and will involve saving all your urine for twenty-four hours in a special bottle that the clinical laboratory will give you. The results will help your doctor evaluate whether it will be safe for you to continue taking lithium.

  An occasional patient will develop a rash, and patients with psoriasis who take lithium will often experience a flare-up of the condition. This may require consultation with a dermatologist, switching to another brand of lithium, going off lithium temporarily, or switching to one of the other mood-stabilizing medications. Acne may also worsen during lithium treatment. This can be treated with antibiotics or retinoic acid, but in some cases the lithium may have to be stopped. Some patients complain of hair loss, but the hair usually grows back, whether or not the patient continues taking lithium. It is interesting to note that lithium-related hair loss occurs primarily in women, and hair can disappear from anywhere on the body. Hair loss is sometimes a sign of hypothyroidism (see below) and so your doctor may order a thyroid blood test if the problem persists.

  Lithium can cause a variety of changes in the electrocardiogram (ECG), but these
are usually not serious. Older patients, as well as those with heart disease, should have an ECG taken before they start on lithium, as noted above. The ECG can be repeated once you are stabilized on lithium to see if there are any changes in heart rhythm that might be a cause for concern.

  You can see in Table 20–12 that lithium can also cause an increase in your levels of white blood cells. These are the cells that normally fight infection. A normal white blood cell count is in the range of 6,000 to 10,000. The white blood cell count in patients on lithium typically increases to the range of 12,000 to 15,000 per cc, elevations that are not considered dangerous. However, if you go to a physician because you are ill, make sure you remind him or her that you are taking lithium and that the lithium may cause a false elevation of your white blood cell count Otherwise, your doctor may falsely conclude that you have a serious infection, even if you actually do not.

  Finally, lithium can affect thyroid functioning in as many as 20 percent of patients. As noted above, one common effect is an increase in the size of the thyroid gland (called a “goiter”) without any changes in thyroid function. Other patients develop increases in the levels of thyroid stimulating hormone (TSH) in the blood. This indicates that the body is trying harder to stimulate the thyroid gland. As many as 5 percent of patients on lithium will develop hypothyroidism, and this may require treatment with thyroxine (0.05 to 0.2 mg per day), a thyroid hormone replacement. Hypothyroidism is more common in women than in men.

  Lithium Drug Interactions. As you can see in Table 20–13 on pages 630–631, lithium interacts with many other drugs. Make sure you review this list with your physician if you are taking other medications at the same time you are taking lithium.