TYPES OF MEDICATION
What are mood stabilizers?
Other anticonvulsants used as mood stabilizers
What are antidepressants?
What are antipsychotic medications?
ACUTE PHASE OF TREATMENT
Selecting a mood stabilizer for an acute manic
How quickly do mood stabilizers work?
Selecting an antidepressant for an acute
Strategies to limit side effects
Almost all people with bipolar
disorder, even those with the most severe forms, can obtain substantial
stabilization of their mood swings. The 3 most important types of medication
used to control the symptoms of bipolar disorder are mood
and antipsychotics. Your doctor may
also prescribe other medications to help with insomnia, anxiety, or restlessness.
While it is unsure how some of the these medications work, it is known
that all of them affect chemicals in the brain called neurotransmitters,
which are involved in the functioning of nerve cells.
are mood stabilizers?
Medications are considered
mood stabilizers if they have 2 properties: 1) they provide relief from
acute episodes of mania and depression, or prevent them from occurring;
and 2) they do not worsen depression or mania or lead to increased cycling.
Lithium, divalproex and carbamazepine meet this definition. The first
2 are the most widely used. Divalproex and carbamazepine were originally
developed as anticonvulsants for the control of epilepsy, another brain
disorder. Electroconvulsive therapy(ECT), is also considered
a mood stabilizing treatment.
Lithium (brand names Eskalith, Lithobid, Lithonate)
The first known mood stabilizer,
lithium, is actually an element rather than a compound(a substance synthesized
by a laboratory). Lithium was first found to have behavioural effects
in the 1950s. Lithium appears to be most effective for individuals with
more "pure" or euphoric mania(where there is little depression
mixed in with the elevated mood). It is also helpful for depression, especially
when added to other medications. Lithium appears to be less effective
in mixed manic episodes and in rapid-cycling
bipolar disorder. Monitoring blood levels of lithium can reduce side-effects
and ensure that the patient is receiving an adequate dose to help produce
the best response. Common side-effects of lithium include weight gain,
tremor, nausea and increased urination. Lithium may affect the thyroid
gland and the kidneys, so periodic tests are needed to be sure they are
functioning properly. Lithium users have been known to get "Hypothyroidism"
which is the decrease of Thyroid levels. This is why Bipolar Disorder
has sometimes been linked to Thyroid Disease.
Divalproex (brand name Depakote)
Divalproex has been used as
an anticonvulsant(to treat seizures) for several decades. It has also
been extensively researched as a mood stabilizer in bipolar illness. Divalproex
is equally effective in both euphoric and mixed manic episodes. It is
also effective in rapid-cycling
bipolar disorder and for those individuals whose illness is complicated
by substance abuse or anxiety disorders. Unlike other mood stabilizers,
divalproex can be given in relatively large doses for acute mania, which
may produce a more rapid response. Common side effects of divalproex include
sedation, weight gain, tremor, and gastrointestinal problems. Blood level
monitoring and dose adjustments may help minimize side effects. Divalproex
may cause a mild liver inflammation and may affect the production of a
type of blood called platelets. Although it is quite rare for there to
be any serious complications from these potential effects, it is important
to monitor liver function tests and platelet counts periodically.
Other anticonvulsants used as mood stabilizers
- Carbamazepine (Tegretol,
Carbatrol). Although fewer clinical studies support the use of carbamazepine,
it appears to have a profile similar to divalproex. It, too, has been
available for many years, and is effective in a broad range of subtypes
of bipolar illness and in both euphoric and mixed manic episodes. Carbamazepine
commonly causes sedation and gastrointestinal side effects. Because
of a rare risk of bone marrow suppression and liver inflammation, periodic
blood testing is also needed during carbamazepine treatment, just as
during treatment with divalproex. Because carbamazepine has complicated
interactions with many other medications, careful monitoring is needed
when it is combined with other medications.
- Lamotrigine (Lamictal).
Lamotrigine is a relatively new medication. Recent research suggests
that it can act as a mood stabilizer, and may be especially useful for
the depressed phase of bipolar disorder. One serious risk of lamotrigine
use is that 3 out of every 1000 individuals(0.3%) taking the medication
develop a serious rash. The risk of rash can be lowered by increasing
the dosage very slowly. Aside from the risk of rash, lamotrigine tends
to have fewer troublesome side effects overall, but can cause dizziness,
headaches, and difficulties with vision.
- Gabapentin (Neurotonin).
Gabapentin has become popular as a mood stabilizer, although there has
been relatively little research on its use in bipolar disorder. It appears
especially helpful in reducing anxiety. One strength of gabapentin is
that it is unlikely to interact with other medications, so that it can
be easily added to other mood stabilizers to augment their effect. Side
effects of gabapentin can include fatigue, sedation, and dizziness.
- Topiramate (Topomax). Preliminary
research suggests that this new anticonvulsant may be helpful in mania.
One side effect of topiramate may actually be an advantage. Unlike many
of the other mood stabilizers, topiramate does not appear to cause weight
gain and may actually help people lose weight. Other side effects may
include sedation, dizziness, and cognitive slowing or memory difficulties.
It should be avoided by people who have had kidney stones.
Antidepressants treat the symptoms
of depression. In bipolar disorder, antidepressants must be used together
with a mood stabilizing medication. If used without a mood stabilizer,
an antidepressant can push a person with bipolar disorder into a manic
state. Many types of antidepressants are available with different chemical
mechanisms of action and side effect profiles. Most research with antidepressants
has been done in people with unipolar depression(people who have never
had a manic episode). In unipolar depression, the available medications
are about equally effective. There has been little research on the use
of antidepressants in bipolar disorder, but most experts consider the
following 3 types to be first choices:
- Bupropin (Wellbutrin)
- Selective serotonin reuptake
inhibitors: fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil),
- Venlafaxine (Effexor)
If these do not work, or they
cause unpleasant side effects, the other choices are:
- Mirtazapine (Remeron)
- Nefazodone (Serzone)
- Monoamine oxidase inhibitors:
phenelzine (Nardil), tranylcypromine (Parnate). These are very effective
but also require you to stay on a special diet to avoid dangerous side
- Tricyclic antidepressants:
amitriptyline (Elavil), desipramine (Norpramin, Pertofrane), imipramine
(Tofanil), nortriptyline (Pamelor). Tricyclics may be more likely to
cause side effects or to set off manic episodes or rapid cycling.
are antipsychotic medications?
Antipsychotic medications are
used to control psychotic symptoms, such as hallucinations or delusions,
that sometimes occur in very severe depressive or manic episodes.
Antipsychotics can be used in 2 additional ways in bipolar disorder, even
if no psychotic symptoms are present. They may be used as sedatives, especially
during early stages of treatment, for insomnia, anxiety, and agitation.
Researchers also believe that the newer antipsychotic medications have
mood stabilizing properties, and may help control depression and mania.
Antipsychotic medications are therefore often added to mood stabilizers
to improve the response in patients who have never had psychotic symptoms.
Antipsychotics may also be used alone as mood stabilizers when patients
cannot tolerate or do not respond to any of the mood stabilizers.
There are 2 kinds of antipsychotics: older antipsychotics(often called
"typical" or conventional antipsychotics) and newer antipsychotics(often
called atypical antipsychotics). One serious problem with the older antipsychotics
is the risk of a permanent movement disorder called tardive dyskinesia(TD).
Older antipsychotic medicines may also cause stiffness, restlessness,
and tremors. The newer "atypical" antipsychotics have a much
lower risk of causing TD(roughly 1% per year) and movement and muscle
side effects. Because of this, the newer atypical antipsychotics are usually
the first choice in any of the situations when an antipsychotic is needed.
Four atypical antipsychotics, are currently available:
- olanzapine (Zyprexa)
- quetiapine (Seroqeul/Seroquel)
- risperidone (Risperdal)
- clozapine (Clozaril)
As mentioned earlier, research
is beginning to show that these atypical antipsychotics have mood stabilizing
properties. Common side effects of the atypical antipsychotics include
drowsiness and weight gain. Although it is very effective, clozapine is
not a first choice medication because it can cause a rare and serious
blood side effect, requiring weekly or biweekly blood tests.
Examples of conventional antipsychotics include older medications such
- haloperidol (Haldol)
- perphenazine (Trilafon)
- chlorpromazine (Thorazine)
Although they are not usually
a first choice, the older medications can be helpful for patients who
do not respond to or have troublesome side effects with the newer atypical
PHASE OF TREATMENT
a mood stabilizer for an acute manic episode
drugs for treating a manic episode during the acute phase are lithium
and valproate. In choosing between these 2 medications, your doctor will
consider your treatment history(whether either of these medicines has
worked well for you in the past), the subtype of bipolar disorder you
have(e.g., whether you have rapid cycling bipolar disorder), your current
mood state(euphoric or mixed mania), and the particular side effects that
you are most concerned about.
Lithium and divalproex are each good choices for "pure" mania(euphoric
mood without symptoms of depression), while divalproex is preferred for
mixed episodes or for patients who have rapid cycling bipolar disorder.
It is not unusual to combine lithium with divalproex to obtain the best
possible response. If this combination is still not fully effective, a
third mood stabilizer is sometimes added.
Carbamazepine is a good alternative medication after lithium and divalproex.
Like divalproex, carbamazepine may be particularly effective in mixed
episodes and in the rapid cycling subtype. It can be easily combined with
lithium, although it is more complicated to combine it with divalproex.
The newer anticonvulsants(lamotrigine, gabapentin, and topiramate) are
often best reserved as back-up medications to add to first-line medications
for mania, or to use instead of the first-line group if there have been
difficult side effects.
quickly do mood stabilizers work?
It can take a
few weeks for a good response to occur with mood stabilizers. However,
it is often helpful to combine mood stabilizers with other medications
that provide immediate, short-term relief from the insomnia, anxiety,
and the agitation that often occur during a manic episode. The choices
for so-called "adjunctive" medication include:
- antipsychotic medicines,
especially if the person is also having psychotic symptoms(see above)
- a sedative called a benzodiazepine.
Benzodiazepines include lorazepam (Activan), clonazepam (Klonopin),
and others. They should be carefully supervised, or avoided, in patients
who have a history of drug addiction or alcoholism.
Although both benzodiazepine
sedatives and antipsychotic medicines can cause drowsiness, the dosages
of these medications can generally be lowered as the person recovers from
the acute episode. However, some individuals need to continue taking a
sedative for a longer period to control certain symptoms such as insomnia
or anxiety. Longer-term treatment with an antipsychotic is sometimes needed
to prevent relapse.
an antidepressant for an acute depression
Although a mood stabilizer
may treat milder depression, an antidepressant is usually needed for more
severe depression. It is dangerous to give antidepressants alone in bipolar
disorder, because they can trigger an increase in cycling or cause the
person's mood to "overshoot" and switch from depression to hypomania.
For this reason, antidepressants are always given in combination with
a mood stabilizer in bipolar disorder.
Antidepressants usually take several weeks to show effects. Although the
first antidepressant tried will work for the majority of patients, it
is common for the patients to go through 2 or 3 trials of antidepressants
before finding one that is fully effective and doesn't cause troublesome
side effects. While waiting for the antidepressant to work, it may may
be helpful to take a sedating medication to help relieve insomnia, anxiety,
If depression persists despite use of an antidepressant with a mood stabilizer,
adding lithium(if not already in use) or changing the mood stabilizer
might help. Lamotrigine, in particular, may be helpful in depression.
to limit side effects
All of the medications that
are used to treat bipolar disorder can produce bothersome side effects;
there are also some serious but rare medical reactions. Just as different
people have varying responses to different medications, the type of side
effects different people develop can vary widely, and some people may
not have any side effects at all. Also, if someone has problems with side
effects on 1 medication, this does not mean that the person will develop
troublesome side effects on another medication,
Certain strategies can help prevent or minimize side effects. For example,
the doctor may want to start at a low dose and adjust the medication to
higher doses very slowly. Although this may mean that you need to wait
longer to see if the medication will help the symptoms, it does reduce
the chances of side effects developing. In the case of lithium or divalproex,
blood level monitoring is very important to insure that a patient is receiving
enough medication to help, but not more than is necessary. If side effects
do occur, the dosage can frequently be adjusted to eliminate the side
effects or another medication can be added to help. It is important to
discuss your concerns about side effects and any problems you may be experiencing
with your doctor, so that he or she can take it into account when planning
Electroconvulsive therapy is
often life-saving in severe depression and mania, but has received a lot
of undeserved negative publicity. ECT is a critically important option
if someone is very suicidal, if the person is severely ill and cannot
wait for medications to work(e.g., the person is not eating or drinking),
if there is a history of many unsuccessful medication trials, if medical
conditions or pregnancy make medications unsafe, or if psychosis(delusions
or hallucinations) is present. ECT is administered under anesthesia in
a carefully monitored medical setting. Patients typically receive 6 to
10 treatments over a few weeks. The most common side effect of ECT is
temporary memory problems, but memory returns quickly after a course of
Many patients with bipolar
I disorder(i.e., patients who have had at least 1 full manic episode)
are hospitalized at some point in the course of the illness. Because acute
mania affects insight and judgment, individuals with mania are often hospitalized
over their objections, which can be upsetting for both patients and their
loved ones. However, most individuals with mania are grateful for the
help they received during the acute episode, even if it was given against
their will at the time. Hospitalization should be considered under the
- When safety is a question
due to suicidal, homicidal, or aggressive impulses or actions
- When severe distress or
dysfunction requires round-the-clock care and support(which is difficult,
if not impossible, for any family to sustain for a long period of time)
- Where there is ongoing substance
abuse, to prevent access to drugs
- When the patient has an
unstable medical condition
- When close observation of
the patient's reaction to medications is required
especially lithium and divalproex, are the cornerstones of prevention
for long term maintenance treatment. About 1 in 3 people with bipolar
disorder will remain completely free of symptoms just by taking mood stabilizing
medication for life. Most other people experience a great reduction in
the frequency and severity of episodes during maintenance treatment.
It is important not to become overly discouraged when episodes do occur
and to recognize that the success of treatment can only be evaluated over
the long term, by looking at the frequency and severity of episodes. Be
sure to report changes in mood to your doctor immediately, because adjustments
in your medicine at the first warning signs can often restore normal mood
and head off a full-blown episode. Medication adjustments should be viewed
as a routine part of treatment(just as insulin doses are changed from
time to time in diabetes). Most patients with bipolar disorder do best
on a combination or "cocktail" of medications. Often the best
response is achieved with 1 or more mood stabilizers, supplemented from
time to time with an antidepressant or possibly an antipsychotic medication.
Continuing to take medication correctly and as prescribed(which is called
adherence) on a long term basis is difficult whether you are being treated
for a medical condition(such as high blood pressure or diabetes) or for
bipolar disorder. Individuals with bipolar disorder are often tempted
to stop taking medication during maintenance treatment for several reasons.
They may feel free of symptoms and think they don't need medication any
more. They may find the side effects too hard to deal with. Or they may
miss the mild euphoria they experience during hypomanic episodes. However,
research clearly indicates that stopping maintenance medication almost
always results in relapse, usually in weeks to months after stopping.
In the case of lithium discontinuation, the rate of suicide rises precipitously.
There is some evidence that stopping lithium in an abrupt fashion(rather
than slowly tapering off) carries a much greater risk of relapse. Therefore,
if you must discontinue medication, it should be done gradually under
the close medical supervision of your doctor.
If someone has had only a single episode of mania, consideration may be
given to tapering the medication after about a year. However, if the single
episode occurs in someone with a strong family history of bipolar disorder
or is particularly severe, longer term treatment should be considered.
If someone has had 2 or more manic or depressed episodes, experts strongly
recommend taking preventive medication indefinitely. The only times to
consider stopping a preventive medication that is working well is if a
medical condition or severe side effects prevent its safe use, or when
a women is trying to become pregnant. Even these situations may not be
absolute reasons to stop, and substitute medications can often be found.
You should discuss each of these situations carefully with your doctor.
Published 2nd May 2001