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.
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
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
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.