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From NAMI -
http://www.nami.org
New Treatment Options For Bipolar Disorder
Compared to the glut of new medications developed in recent years for
the treatment of such serious mental illnesses as schizophrenia and
depression, the lack of advances in new drug options for those with
bipolar disorder (manic depression) has proven increasingly frustrating
and disappointing. Currently, the mood stabilizers available for those
with manic depression are limited to the old standby lithium (Eskalith,
Cibalith-S, Lithobid) and the newer divalproex sodium (Depakote). While
these medications have proven helpful for many, there is a substantial
group of those with bipolar disorder who have either not benefited from
these options or experience problematic side effects. Furthermore, some
feel that lithium and Depakote are better at treating mania than
depression, and using antidepressants with these drugs has been known to
trigger mania or rapid cycling-conventional antidepressants may not be as
effective in treating depressive episodes related to bipolar disorder as
they are for treating such episodes in those with unipolar depression. For
such reasons, many clinicians have begun to experiment with drugs that are
indicated for the treatment of other illnesses, but have proven effective
in the treatment of those with bipolar disorder in some studies. This type
of medication usage is known as "off label."
Note: It is important to recognize that "off label" usage is
generally considered an option only after all traditional treatment
methods have failed. Like all medications, these new drugs work
differently for different people and each has its own unique side effects.
Although the discovery of the effectiveness of these medications in some
cases points to a future filled with newer and better options for those
with bipolar disorder, many more controlled studies need to be conducted.
These drugs have not been approved by the Food and Drug
Administration (FDA) for the treatment of bipolar disorder.
The type of medication used most often for bipolar disorder in an "off
label" capacity is the group known as anticonvulsants. Used
primarily for the treatment of epilepsy, several of these drugs have
recently shown promise in treating those with manic depression,
particularly in helping stabilize mood.
 | Tegretol (carbamazepine): Due to its apparent effectiveness
as a mood stabilizer, Tegretol has become a first-line treatment option
even though it has never received FDA approval for the treatment of
bipolar disorder. The most common side effects seen with Tegretol
include dry mouth and throat, constipation, impaired urination,
decreased sense of taste, dizziness, drowsiness, unsteadiness, loss of
appetite, nausea, vomiting, indigestion, and diarrhea. Some individuals
may also experience clumsiness, double vision, edema (excess of fluid in
tissue or body cavity), skin rash, and cardiovascular complications.
Additionally, there is the possibility of such life-threatening adverse
effects as suppression of blood cells that fight infection or prevent
bleeding. The drug can also have negative interactions with Prozac,
Luvox, and lithium. Furthermore, it should not be taken with monoamine
oxidase inhibitors (MAOIs) and should not be used by those pregnant or
nursing. Lastly, regular blood count monitoring and periodic liver
function tests are mandatory-due to the induction of enzymes in
the liver by carbamazepine, several adverse interactions can occur when
it is combined with other drugs. |
| Lamictal (lamotrigine): Several studies (including a
randomized, double-blind, placebo-controlled trial presented at the 1998
American Psychiatric Association's annual meeting) indicate that
Lamictal may also help stabilize mood in those with bipolar disorder.
The drug has been reported as being a more potent antidepressant than
Tegretol or Depakote, and it appears to have a low incidence of such
side effects as weight gain and hair loss. Although it seems that
Lamictal can be taken with MAOIs, taking the drug concurrently with
Tegretol may increase the chance of adverse side effects. The most
commonly reported side effects are dizziness, headache, double vision,
unsteadiness, nausea, blurred vision, sleepiness, rash, and vomiting.
Special attention should be paid to skin rashes, which in some extreme
cases have developed into the severe disorder known as Stevens-Johnson
syndrome or caused death. Any noticed rash should be reported
immediately to a doctor. The concurrent use of Depakote increases the
risk of developing a rash. |
| Neurontin (gabapentin): Also proven effective as a mood
stabilizer for those with bipolar disorder, Neurontin is chemically
unrelated to any other anticonvulsant. The drug has been the subject of
several studies as well, two of which were presented at this year's APA
meeting. Like Lamictal, Neurontin has exhibited a lower incidence of
side effects (weight gain, hair loss) than lithium and Depakote. As
opposed to Lamictal, Neurontin appears to work more in alleviating mania
than depression. It also seems to be a more potent antianxiety agent
than both Depakote and Tegretol. Additionally, there have been no
reports of Neurontin interacting negatively with MAOIs, lithium,
Depakote, or Tegretol. Side effects most often noted include sleepiness,
dizziness, unsteadiness, nystagmus (rapid, involuntary fluctuation of
the eyeballs), tremor, and double vision. A distinct disadvantage to the
drug is that it needs to be taken up to four times a day, compared to
twice a day for other anticonvulsants. |
| Topamax (topiramate): Yet another anticonvulsant that seems
to help regulate mood in those with manic depression, Topamax has been
the subject of a few open-label studies. The apparent advantage of this
anticonvulsant over the others is that it does not seem to cause weight
gain; it may actually help individuals lose weight. On the other hand,
Topamax appears to cause more cognitive side effects than the other new
drugs. Other commonly reported side effects include sleepiness,
dizziness, vision problems, unsteadiness, speech problems, psychomotor
slowing, "pins and needles," nervousness, nausea, memory problems,
tremor, and confusion. Topamax does not seem to interact negatively with
MAOIs, lithium, Lamictal, or Neurontin, but a combination of the drug
with Depakote or Tegretol can lower plasma levels of Topamax. |
| ABS-103: This drug is currently in preclinical studies
evaluating its treatment potential for epilepsy, migraine headaches, and
mania. Evidence suggests it may be as effective as Depakote and not
cause as many side effects. In fact, ABS-103 might prove safe for women
of childbearing age. |
The new generation of drugs used to treat schizophrenia, known as
atypical antipsychotics, have also been explored in some studies as
potential treatment options for individuals with bipolar disorder.
| Zyprexa (olanzapine): Although recently turned down by the
FDA to be marketed for the treatment of bipolar disorder, Zyprexa has
shown antimanic effectiveness in some trials when used in conjunction
with other medication. One adverse effect, excessive weight gain, can be
problematic in some patients and may lead to nonadherence. |
| Seroquel (quetiapine fumarate): Another atypical
antipsychotic currently being investigated for use in those with bipolar
disorder.
(Note: Separate fact sheets on the above two medications and their
uses for the treatment of schizophrenia are available from the
NAMI HelpLine.)
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Substance P-blockers are one other type of newly developed
medication that also shows potential promise in helping regulate mood.
This class of drugs derives its name from how it works; unlike SSRIs,
which work by blocking the brain chemical serotonin, these medications
block a brain chemical known as substance P. Substance P was discovered in
1931, and medications designed to work against the chemical have often
been used experimentally, but never successfully, in attempts to treat
such conditions as chronic pain, migraine headaches, anxiety, and asthma.
A recent study of a substance P-blocker called MK-869 found the
drug to work as effectively as and cause less of certain sexual side
effects than the SSRI Paxil.
Please remember: While all of the medications mentioned above
have proven effective in certain studies, there is still quite a way to go
in getting approval by the FDA for their use in the treatment of bipolar
disorder. We will keep you notified about any changes in status.
Reviewed by David J. Kupfer, M.D., Thomas Detre professor and chair
for the Department of Psychiatry and director of research at Western
Psychiatric Institute and Clinic
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