Treatment of Bipolar Disorder by M. Glaser, MD

Bipolar disorder requires medication, usually
life long. Most patients treated for bipolar
disorder require more than one medication
to control the symptoms. You can compare
it to the treatment of high blood pressure.
Like in high blood pressure, one can live a
lifestyle that is healthy and take medication
to have the best outcome possible. Treated
and controlled high blood pressure is not
problematic. Untreated high blood pressure
is severely problematic. Well, bipolar
disorder is the same. If a person with bipolar
disorder lives a healthy lifestyle and takes
medication, then severe problems are usually
prevented. The medications preserve brain
functioning and prevent brain damage that
bipolar disorder causes.

Bipolar disorder has two parts, mania and
depression. Some medications treat the
mania as well as anger while others treat only
depression while others treat both. First I will
describe the medications that treat mania
and then the medications that treat both
mania plus depression.

It is important to note, I will succinctly
describe each medication with its most
serious side effects. For all the medications I
list below, their serious side effects are
extremely rare and infrequent. However, I
will not sugar cote the information. Some
side effects are not entirely known, therefore
there are times when I give you my editorial
opinion based on my experience and
knowledge as a physician. New side effects
are often discovered years after a medication
is introduced.

The medications for bipolar disorder fall into
three main groups. One is the second
generation antipsychotics, second is the
antiseizure medications, and third is lithium.

Lithium is the oldest treatment for bipolar
disorder and has been used in psychiatry for
several decades. Some say that Cuban cigars
are so well liked because of the high
amounts of lithium in Cuban soil. Lithium
works best for classic bipolar disorder that
includes distinctive episodes of mania (high
energy plus euphoria) not mixed with other
symptoms like hallucinations or depression.
Lithium is very inexpensive to prescribe and
since it has been around so long, its side
effects are generally understood. Most
people who take lithium do not have any
serious side effects. The serious ones include
hypothyroidism (this means low thyroid
hormone which regulates your metabolism
so if it is hypo you will feel tired and cold).
Other important side effect risks are a hand
tremor, acne, weight gain and increased
urination do to kidney irritation and possible
injury. Hair loss can also happen. In growing
bones, lithium does get deposited in the
bone structure, with unknown effects.
Periodic blood levels must be checked for
lithium to make sure the level is not to low or
to high. Lithium at too high a blood level in
you body can be toxic and cause a heart
attack. The window is

The second oldest group of medications with
known benefits for bipolar disorder are the
antiseizure medications. These are Depakote,
Tegretol, Lamictal, and Trileptal. Other
antiseizure medications such as Neurontin
and Trileptal are also used for bipolar
disorder but there are no studies supporting
there use for bipolar in children and spars
data for treatment in adults. In fact there is
evidence that they are not effective.
Trileptal's benefit for bipolar, in my opinion,
has not been completely settled.

First is Depakote (valproic acid). This has
FDA approval to treat manic(increased energy
plus euphoria) and mixed(increased energy
plus depression or rage) episodes. It has no
proven benefit for depressed episodes nor
have I seen it help depressed episodes in my
practice. My experience with Depakote is
that most patients gain lots of weight.
Depakote also requires monitoring of blood
periodically to check for potential liver injury
and low blood counts. There is one study of
patients in Europe. The patients were all
female with seizures who took Depakote
prior to puberty. There was an extra ordinary
high rate of polycystic ovary disease which
causes sterility possibly due to a Depakote
side effect. Please note that these are all
extremely, extremely, rare side effects. Also,
since we know what level Depakote must be
at in your system to know if it will work, we
also periodically check blood levels of the
med. Too high a level can be toxic and too
low will not help.

Tegretol (carbemazapine) is the second most
common antiseizure medication used for
bipolar disorder. There is not as much
evidence for it as there is for Depakote but a
considerable amount of data shows it to be
effective for manic phases. Some
psychiatrists prefer Depakote and Tegretol
for anger problems but I prefer the second
generation antipsychotics for anger/rage
issues. Tegretol has very very rare but
serious side effects. The overwhelming
majority of patients do not experience them
just like with most of the medications I
describe in this section, the side effects
generally do not happen. However, Tegretol's
risks include low white blood cell count. If
this happens, the patient is unable to fight
off infections. Thus, blood must be checked
periodically. Another rare but serious side
effect is Stevens-Johnson syndrome. This is
a rash that is so severe it could kill the
person. Blood levels must be checked to
avoid too low a level or too high a level that
could be toxic.

While taking this medication, notify your
doctor if you experience any rash and stop
taking Tegretol until you talk to your doctor.
You should also take Benadryl 50 mg every
12 hours and apply hydrocortisone cream to
the rash four times a day.

Lamictal is the newest antiseizure medication
for bipolar disorder. It was the first to be
approved by the FDA for the depressed
phase of bipolar disorder. It has also shown
to help mania as well. Weight gain does not
occur as much as with Depakote. Blood
draws are not required. It is newer, so side
effects are not as well established as with
Depakote and Tegretol. The most serious
side effect is a rash similar to Tegretol but
with greater frequency.

The rash is called Stevens-Johnson
syndrome and can be deadly. If you get a
rash of any size, stop taking Lamictal and
call your doctor emergently. Follow the
instructions above for Tegretol.

In order to minimize the risk of a rash, the
dose of lamictal is started very low and takes
several weeks or months to get to a
therapeutic level. My experience with this
medication is more limited than with the
others. However, I have yet to be impressed
with its efficacy.

Topomax, is a great medicaton because it
usually causes weight loss and thus is very
expensive. However, there are no studies
supporting its use in bipolar disorder and it
may even worsen a person's mood.
Topomax can cause a person to feel mentally
slow. On the other hand, Topomax is a
fantastic anti-migraine head ache
medication. It works great, when taken every
day, at preventing migraine head aches.

The next group are the second generation
antipsychotic medications. These
medications were originally invented to treat
psychosis (delusions or hallucinations) but
were then discovered to help bipolar disorder
as well. Most are FDA approved to treat
bipolar disorder and are now nearly as often
prescribed for bipolar as they are for
psychosis. The names of these medications
are Zyprexa, Abilify, Risperdal, Seroquel, and
Geodon. Geodon has no FDA approval for
bipolar disorder so it will not be discussed
here. The "grand daddy" of all psych meds is
Clozapine, but due to its severe risk of side
effects, it also will not be discussed here,
other than the fact that it probably works the

My first choice in this group of medications
is Abilify (aripiprazol). I have found that it is
the best tolerated by my patients. It has
been shown in studies to treat mania, mixed
episodes, and adjunctive treatment of
another illness called major depression. It
has not yet been shown to help bipolar
depression. Its main side effect risk is
tardive diskenesia. This is a permanent, slow
writhing movement of the hands, body, or
face. This risk is very rare and I have yet to
see it in my practice resulting from Abilify.
All medications in this class have a very low
risk of diabetis. It is likely, but not proven
that Abilify's risk is the lowest within this
group at causing diabetis. Again, this risk is
very, very low. The benefits if Abilify versus
the other medications to chose from are as
follows. It generally does NOT cause
tiredness or a "zombie" feeling and it usually
does not cause weight gain. It also does not
raise cholesterol like the other meds in the
group can do. Another huge benefit is that
Abilify has a unique mechanism of action
that allows it to also help with improving
attention span and reducing hyperactivity.
The mechanism involves Abilify's effect on
the dopamine receptor. Abilify will stimulate
the dopamine receptor like a stimulant
where dopamine is low and block the
receptor like a mood stabilizer where
dopamine is high. This is helpful in patients
with combination ADHD plus Bipolar
disorder. On the other hand, if the dose of
Abilify is too high, it can worsen hyperactivity
and cause a patient to feel restless and
unable to sit still.

Another rare and temporary side effect of
abilify is called acute dystonic reaction. This
side effect will go away on its own once
abilify is stopped. Acute dystonic reaction is
when a muscle, usually in the face, eyes,
mouth, or neck becomes "locked". For
example the head can turn or the eyes can
look up and the person can not change the
direction the muscle has locked into.
Usually, there is also intense pain with the
locked muscle. If this occurs, take 50mg of
Benadryl (dyphenhidramine) by mouth. If the
locked muscle prevents you from being able
to swallow, go to an emergency room to get
a shot in the arm of benadryl or cogentin
(benztropine). Either rout of getting the
antidote in your body will resolve the
symptoms in 15 minutes or less. The patient
should also stop taking abilify and call the

Seroquel is very helpful for bipolar disorder.
Its pros are that it helps both manic and
depressive phases of bipolar disorder. If a
person has trouble sleeping, Seroquel is
extremely helpful for sleep. Seroquel
probably has the lowest risk of tardive
dyskanesia in this group. It does not cause
restlessness at higher doses. The negatives
are higher rates of sedation, increased levels
of cholesterol and lipids, and likely higher
risk of diabetis then some of the others in
this group, although not for certain.

Risperdal (risperidal) is the first widely
prescribed second generation antipsychotic.
Thus, a strong positive is that it has the most
research done on it and we know more about
it than the others in this group. There are
less unknowns about this medication. It
works well for psychosis, and it also helps
with mania and likely helps with depression
but has no FDA approval for this. Risperdal
is generic thus it is the least expensive.
Risperdal is uniquely beneficial for patients
with autism and is FDA approved for the
treatment of behavioral problems associated
with Autism. Risperdal's negatives are as
follows. It often causes weight gain and
daytime sedation. It has a risk of tardive
dyskenisia. It has a similar to slightly less
risk of diabetis as seroquel. It greatly
increases prolactin. Usually this does not
cause any apparent difficulties and requires
no action. Prolactin is a hormone secreted
by the pituitary gland at the base of the
brain. It stimulates breasts to secrete milk in
nursing mothers. I am unsure what effect a
four fold increase in prolactin does to a
person. Very rare symptoms of
increasedprolactin include lower sexual
functioning, breast development in boys or
girls, and unknown risks of activating tumor
cell growth. A newer form of Risperdal
called Invega has recently been released. It
has a similar profile to Risperdal but is more
expensive than Risperdal The above side
effects can be serious but are extremely rare.
Because risperdal has been around a while
and has been shown to be safe in children
and adults, it is often the first choice of many
psychiatrists for their patients.

The last medication in the group is Zyrexa. It
is a newer form of the medication clozapine
(Clozaril). Clozapine has a risk of
agranulocytosis that requires weekly to
monthly blood draws for the entirety of one
taking the medication. It, however has been
shown in study after study to work the best.
On the other hand, it also has other serious
side effects that preclude it from being used
except in the most treatment resistant cases.
Because Zyprexa is similar, it retains some of
clozapine's pros and cons. Zyprexa probably
works a little better than the other
antipsychotics. But it probably has the
greatest weight gain and increase in
cholesterol. It is mildly to moderately
sedative in the daytime. While it is
completely undecided at this time, my own
medical opinion is that Zyprexa probably has
a slightly higher risk of diabetis than most of
the other meds in this group. But I strongly
reiterate, this is not a settled issue and more
information is still needed to say for sure,
one way or the other. Tardive dyskenisia is
also a risk with Zyprexa.


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