Mood Stabilizing Medications

Mood stabilizing medications such as lithium are often used to augment an antidepressant if the antidepressant alone is not fully effective. The classic medication in this class is lithium, although more recently it has been demonstrated that carbamazepine (Tegretol) and valproate (Depakote) are also useful to help some consumers stabilize their moods. Drugs called calcium channel blockers that are typically used to control angina (heart pain) might also have a role to play in some consumers with mood disorders. These drugs are not uppers or downers or antidepressants, but are rather "mood stabilizers". That is, they stabilize both the highs and the lows of some consumers with mood swings.

A. Lithium

Lithium is the drug of choice for consumers with manic depression (Bi-Polar Disorder). It decreases the frequency of the manic episodes and their severity, but it does not necessarily eliminate them in all consumers. It is also useful in aborting the acute manic attack and is often used in combination with one of the antipsychotic drugs. The antipsychotic will slow the consumer down to manageable levels, while lithium is specific for aborting the manic attack itself.
There is also increasing evidence that lithium is useful in schizoaffective disorder and even helps some agitated or aggressive schizophrenic consumers. Consumers who are hyperactive with pressured speech should be considered as potential lithium candidates even if they carry a schizophrenic diagnosis. A certain percentage of lithium responders have previously been given a diagnoses of schizophrenia. These consumers may have carried a schizophrenic diagnosis over many years, and they can at times be paranoid with all of the first rank symptoms of schizophrenia. It probably makes sense to seriously consider a trial of lithium with any schizophrenic consumer who is not responding well to more traditional therapy and who is irritable, angry or aggressive, all of which are affective (mood) symptoms. It is important to remember whenever using a medication but especially when initiating such trials that they are just that-trials. The medication should be started and continued for a specified period of time, usually 4 to 6 weeks, while following symptoms that have been clearly identified before the trial was started. (If someone is not doing well on a medicine, the 'solution' should not be to give up. It should be to try something else. You may have to work hard to convince the doctor of that if your doctor is not enlightened.-ed.)
If you have a family history of manic-depressive disorder, depression, suicide, that increases the probability that lithium should be tried. Likewise if you have other family members who have responded to lithium and/or responhave a family history of alcoholism it might also be a positive sign that lithium will work. A consumer who reports both depressions and "highs", or bouts of excessively spending money or frequent impulsive marriages should raise the index of suspicion about the diagnosis.
Lithium is also helpful in prevention of the depressive side of manic depressive disease and in recurrent depression. Recent research has indicated that that lithium plus antidepressants are very effective in treating some consumers who have never responded to antidepressants alone.
Lithium has also effective in some consumers with explosive and uncontrollable anger characterized by a "hair trigger" that does not leave time for the consumer to consider the consequences of his behavior. Another controversial use is in consumers with "episodic character disorders" who are often lumped with borderline consumers but show marked variation in affect (mood). This entire area, and even the use of this diagnosis, is controversial.

1. Specifics of Lithium Use

Before starting lithium, a serum BUN (blood urea nitrogen) and serum creatinine test should be given by the doctor to determine that the consumer's kidneys are working properly. Lithium is excreted by the kidneys, and if they are not working properly the lithium can rapidly build up to toxic levels. An EKG is suggested by some experts but it is unclear what it really adds unless there is concern about heart disease. Some experts suggest a creatinine clearance test as well, but this requires collecting all of a person's urine over 24 hours, and is therefore cumbersome, expensive and usually impossible in an outpatient setting. Following serum creatinine over the course of lithium therapy is a reasonably safe alternative as a way of detecting early kidney damage, but even this is probably unnecessary. Despite the early concern about lithium and kidney damage, such damage seems extremely rare. A thyroid screen is also often recommended before starting lithium. Lithium is known to interfere with thyroid function and is may be useful to get a baseline test.
You will usually start by getting 600 to 1200 mg/day of lithium carbonate in divided doses. Lithium carbonate usually comes in 300 mg capsules so a typical dose is three to four capsules a day. Lithium used to always be given 2 or 3 times a day because of concern of toxicity and side effects. More recently it has been demonstrated that most consumers do well taking their entire lithium dose at one time, along with a meal so that there is some food in their stomach to decrease gastrointestinal side effects.
The doctor should follow your serum lithium levels (take blood samples -ed) and adjust the dose so that the lithium level in the blood is 0.6 to 1.2 meq/1. The textbooks used to suggest that consumer should have lithium levels between 0.8-1.2. Recent research has suggested that consumers have fewer relapses if their lithium is kept between .8 and 1.0 meq/l than if their level is allowed to drop to the 0.4 to 0.6 meq/l range. Unfortunately they also have poorer compliance and more side effects at the higher levels. While there is some increased risk of relapse in the lower dose, for some consumers the decrease in side effects may make this risk worthwhile. Most consumers will require between 600 and 1800 mg/day to maintain their serum lithium level within this therapeutic range. Older consumers and consumers with brain damage generally require less lithium and may become toxic on normal doses. As consumers end a manic episode it generally requires less of the drug to maintain the same serum drug level, and consumers who have had a stable lithium level while manic might become toxic if they continue to take the same amount of lithium after they calm down. Conversely, consumers going into a manic episode will frequently need to increase their daily lithium dose to maintain a therapeutic serum lithium level.
After a consumer seems stable on a given dosage of lithium, the blood levels can be measured at decreasing intervals to a maximum of about every three months. Blood levels change during the day, peaking several hours after the consumer takes a dose, and dropping slowly until the next dose. It is important, therefore, to standardize when the blood sample is drawn. A serum level of .6 meq/L 12 hours after a dose is different than the same level 24 hours after a dose. Standard serum levels should always be taken 12 hours after taking a normal dose of medication. A consumer receiving divided doses of lithium during the day should have his lithium level checked in the morning before he receives his first dose for the day and about 12 hours after his/her evening dose of medication.
Standard textbooks suggest that a serum creatinine should be measured every 6 months, and a thyroid screen should be repeated every year or so. Actually is it very unclear if these routine screenings are necessary. More importantly, one should be suspicious and obtain thyroid functions tests if there are any symptoms of hypothyroidism (underactive thyroid). These symptoms can include excessive fatigue, extreme weight gain, constipation, intolerance to cold, and dry skin or hair.

Some of the side effects from lithium can be treated. Mild diarrhea can be treated by over-the-counter medications such as Kaopectate. The fine tremor sometimes caused by lithium can be treated with low dose propranolol. Propranolol is relatively safe, easy to use, and effective. Still, using one drug to treat the side effects of another drug only makes sense for those consumers where the tremor is causing some problem or discomfort. If increased urination becomes a serious problem for the consumer, either because of dehydration or by becoming so frequent that it is interfering with the consumer's life, it can be treated by giving the consumer hydrochlorothiazide. This is a diuretic that normally causes people to urinate more, but works paradoxically on consumers suffering from increased urination because of lithium. There is some concern that this may potentially increase the risk of kidney damage from lithium, and is only used when the increased urinary frequency is severe. Hydrochlorothiazide increases most consumer's serum lithium levels, potentially to toxic levels. To prevent lithium toxicity, the dose of lithium is usually decreased at the same time that hydrochlorothiazide is started, and serum lithium levels need to be monitored carefully.
Alcoholic consumers on lithium present a special problem in that during drinking binges they may become dehydrated, thereby secondarily increasing their serum lithium levels enough to become toxic. The acute organic brain syndrome might be from lithium as well as alcohol. This is rarely a problem because these consumers rarely take their meds while drinking, but an emergency lithium level is indicated for anyone who is drunk and/or dehydrated while on lithium.

2. Side Effects of Lithium:

a. Effects on the Kidney: Increased fluid intake and urination is found in most consumers on lithium because of its direct effect on the kidneys. In some rare consumers this increased urination may be severe enough to cause a serious dehydration. Lithium is excreted by the kidneys and preexisting kidney disease (as demonstrated by BUN and serum creatinine tests) can allow a dangerous build up of the drug in a short time. In almost all individuals these kidney effects are more inconvenient than dangerous, and correct themselves when the medication is discontinued. There has been concern that some few consumers on long term lithium therapy may incur permanent, irreversible and potentially life threatening kidney damage. No clear information about the frequency of such damage is available, except that it seems to be extremely rare and can be prevented by discontinuing lithium before the kidney damage gets too severe. All consumers on lithium should have their serum creatinine measured every 6 months to detect early kidney damage.

b. Thyroid Effects: Lithium decreases the output of thyroid hormone and hypothyroidism should be considered in consumers on long term lithium therapy (symptoms include weight gain, depression, rough dry skin and brittle dry hair, increased susceptibility to cold).

c. Common, Uncomfortable Side Effects of Lithium: The most common side effect of lithium is a fine tremor of hands that usually begins in the first few days of treatment. Nausea, vomiting or mild abdominal pain, fatigue and thirst are also common initially, but usually disappear in a few weeks. These side effects may be decreased by giving the drug in smaller divided doses or giving it along with food so that absorption from the stomach is slowed down. A metallic taste is common. Weight gain is frequently reported, and increased thirst and urination is almost very common. Lithium can affect the heart and causes minor changes in the EKG in almost all consumers. This is rarely a serious problem.

d. Toxic Side Effects: Toxic side effects of lithium initially include thirst, decreased appetite, vomiting and diarrhea. These can progress to confusion, coarse tremor, muscle twitching, and slurred speech. Finally, the consumer appears drunk with muscle twitches, nystagmus (small jerks of the eye), hyperreflexia (increased reflexes), seizures, stupor and eventually coma.
If a consumer taking lithium develops diarrhea or nausea, lithium intoxication should be considered and serum lithium levels obtained.

e. Drug Interactions: Lithium interacts with a number of commonly prescribed medications. The most common problem is a rise in the serum lithium level, at times to toxic levels, when a consumer who had been stable on lithium now begins taking another medication at the same time. This occurs with hydrochlorothiazide, a very common medication used for water retention and high blood pressure, and with a number of pain medications including most of the non-steroidal anti-inflammatory medications like indomethacin (Indocin), phenylbutazone (Butazolidin), and possibly ibuprofen (Motrin). Aspirin and acetominophen (Tylenol) are safe.

f. Use of Lithium in Pregnancy: There is good evidence that lithium increases the risk of serious birth defects, especially if taken during the first three months of pregnancy. This risk is high enough that women who become pregnant or who are planning to become pregnant should stop taking lithium if at all possible.

B. Carbamazepine (Tegretol)

There has been growing interest in the use of anticonvulsant medications in consumers where there is no demonstrated seizure activity. It was suggested several years ago that phenytoin (Dilantin) may have behavioral effects in some psychiatric consumers, helping some and seeming to make others worse. There had been speculation that some consumers diagnosed as schizophrenic may actually have temporal lobe epilepsy or some other abnormal brain activity that shows up as psychosis rather than seizures. This continues to be controversial, and even if true it would probably affect a very small number of consumers. (For technical reasons, an abnormal EEG can diagnose epilepsy but a normal EEG does not rule epilepsy out).

1. Clinical Indications of Carbamazepine (Tegretol)

Recently, there has been growing evidence that carbamazepine (Tegretol) is useful in some manic-depressive consumers or consumers with manic type mood swings who do not respond well to lithium, or who cannot tolerate lithium because of side effects. Carbamazepine is definitely worth trying in manic-depressive consumers who are relatively compliant but non-responsive to lithium. Tegretol can be used along with lithium, especially if there has previously been a partial response to the lithium. It seems to be particularly useful in consumers with atypical illness or rapid cycling manic depressive disorder, more than two episodes a year. It has also been used successfully in certain consumers with very resistant depressions, usually in combination with other medications.
Carbamazepine is also being used in a variety of other conditions where lithium has been tried without effect. Some consumers with schizophrenia whose ongoing mood swings makes stabilization difficult respond well to either lithium or carbamazepine in combination with an antipsychotic medication. Some consumers with aggressive or violent outbursts also seem to respond to carbamazepine or one of the other anti-seizure medications. It had previously been thought that these consumers must have some kind of occult seizure disorder causing their outbursts, but carbamazepine seems to be effective in many consumers that have no evidence of any kind of seizures.

2. Side Effects of Carbamazepine (Tegretol)

Carbamazepine does have some significant side effects. Sedation is common, and a drunk-like sense of clumsiness and nausea are not uncommon. More rarely, carbamazepine is known to cause a rare but very dangerous condition where the body stops making white blood cells (aplastic anemia). This is reversible if diagnosed in time, but can easily be fatal if allowed to continue. Any consumer taking carbamazepine who gets an infection, fever, sore throat or mouth sores should immediately get a CBC (complete blood count). In addition, carbamazepine serum levels and CBCs need to be obtained on a regular basis as long as the consumer is taking the drug.
Carbamazepine has recently been associated with a set of birth defects similar to the defects caused by another anticonvulsant, hydantoin (Dilantin).

C. Valproate or Valproic acid (Depakene or Depakote)

There is increasing evidence that valproic acid (Depakene or Depakote), another anticonvulsant, also has mood stabilizing properties. It is generally considered a third line medication, after lithium and carbamazepine (Tegretol) have already been tried.

1. Specifics of Valproate use: Valproic acid is typically started with 250 mg tablets twice a day, and slowly increased to the 1000-1500 mg/day range. It is possible to use blood levels to adjust dose, but the suggested ranges for an adequate serum levels were developed for the amount of medication needed to prevent seizures. There is little research on what is an effective serum range when using valproic acid as a mood stabilizer.

2. Side Effects of Valproate:

The most common side effects are nausea, vomiting and indigestion. Depakote is valproic acid packaged in a coated, time release pill that seems to cause less gastrointestinal (stomach) upset than Depakene, which is the uncoated pill of the same medication. Sedation has been reported although this is less common than with carbamazepine (tegretol). The most serious problem with valproic acid is rare but very serious problems with liver toxicity. This toxic effect on the liver seems most common during the first six months that the medication is being used. Regular liver function tests should be obtained, and any signs of jaundice (yellow skin, yellow eyes) or increased nausea should be followed by liver function tests. Valproic acid has also been reported to interfere with the ability to make white blood cells, but this seems less common than with carbamazepine.

This material was created by Ronald J Diamond, M.D.
University of Wisconsin Department of Psychiatry.


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