Bipolar World thanks Dr. Ivan Goldberg, MD for permission to use this
FAQ.
revised Dec 5, 1999
FAQ: Topiramate (Topamax), Mood
Disorders and PTSD.
NOTE: Topiramate is only approved for the
treatment of people with seizures. There are
no systematic studies that establish the safety
or efficacy of topiramate as a treatment
for people with mood disorders or PTSD.
While such studies are getting underway, what is
currently known about the use of topiramate
for the control of mood disorders and PTSD comes
from uncontrolled case reports.
1. What
is topiramate (Topamax)?
Topiramate
is an anticonvulsant that is chemically unrelated to any other
anticonvulsant
or mood regulating medication. The mechanism of action is
unknown.
2. When
was topiramate approved for marketing in the USA and for what
indications
may it be promoted?
topiramate
received final approval for marketing in the USDA on 24
December
1996 and is labeled for use as an anticonvulsant.
3. Is a
generic version of topiramate available?
There is
no generic topiramate as the manufacturer has patent protection.
4. How does
topiramate differ from other mood stabilizing drugs?
Topiramate
differs from other mood stabilizing drugs in two major ways:
1. topiramate's
frequent effectiveness for patients who have failed to respond
to antidepressants
or mood stabilizers;
2. topiramate's
unique side-effect profile.
5. What,
if anything, uniquely distinguishes topiramate from carbamazepine and
valproate?
Topiramate
has been successful in controlling rapid cycling and mixed bipolar
states
in people who have not received adequate relief from carbamazepine
and/or
valproate.
6. People
with what sorts of disorders are candidates for treatment with
topiramate?
It is too
early to be very specific about which mood disorders are most likely
to respond
to treatment with topiramate. There are just about no published
reports
on topiramate's use in psychiatry. Patients with hard-to-treat bipolar
syndromes
have been treated more often than patients with
"treatment-resistant"
unipolar disorders.
topiramate
seems especially useful when it comes to treating people who have
become
manic as the result treatment with lamotrigine.
There has
recently been a report regarding the control of the symptoms of
PTSD by
topiramate.
7. Is topiramate
useful for the treatment of acute depressed, manic and mixed
states,
and can it also be used to prevent future episodes of mania and/or
depression?
The initial
use of topiramate was to treat people with depressed, manic
rapid-cycling,
and mixed states that did not respond to existing medications.
Some patients
are now being maintained on topiramate on a long term basis
in an attempt
to prevent future episodes. The effectiveness of topiramate as a
long-term
prophylactic agent is currently being established.
8. Are there
any laboratory tests that should precede the start of topiramate
therapy?
Before topiramate
is prescribed the patient should have a thorough medical
evaluation,
including blood and urine tests, to rule out any medical condition,
such as
thyroid disorders, that may cause or exacerbate a mood disorder.
9. How is
treatment with topiramate initiated?
Topiramate
is usually initially prescribed at an initial dose of 12.5 -25 mg once
or twice
a day and the total daily dose is increased by 12.5 - 25 mg every week.
When prescribed
in addition to other anticonvulsants being used as mood
stabilizers,
the final dose is often between 100 and 200 mg per day. Some
patient
with Bipolar Disorder do well on as little as a total daily dose of 50
mg/day.
When used for the control of the symptoms of PTSD the average
final dose
is about 175 mg/day (with a range of 25 - 500 mg/day).
10. Are
there any special problems prescribing topiramate for people taking
lithium,
carbamazepine (Tegretol), or valproate (Depakene, Depakote)?
An interaction
between lithium and topiramate has not been reported.
Carbamazepine
and valproate both have the ability to lower plasma levels of
topiramate
. . . carbamazepine by about 50% and valproate by about 15%.
Topiramate
has no effect on the plasma level of carbamazepine but can
reduce
the plasma level of valproate by about 10%. Pharmacokinetic
interactions
between topiramate and either lamotrigine (Lamictal) or
gabapentin
(Neurontin) have not been reported.
11. What
is the usual final dose of topiramate?
When used
as a mood-stabilizing agent the final dose of topiramate is most
often between
50 and 200 mg/day. Some people require doses as high as 400
mg/day
to achieve a good mood stabilizing effect . . . especially when
topiramate
is being used as a monotherapy . . . while others do fine on 25
mg/day.
12. How
long does it take for topiramate to 'kick-in?'
While some
people notice the antimanic and antidepressant effects early in
treatment,
others have to take a therapeutic amount of topiramate for up to a
month before
being aware of a significant amount of improvement.
13. What
are the side-effects of topiramate?
Here is
a listing of topiramate's side effects that affected 10% or more of the
711 people
taking the drug during clinical trials and the frequency of those
side effects
in the 419 people treated with placebo in those trials:
Common Adverse Reactions (%)
(Topiramate = 200 mg/day)
Adverse Reaction Topiramate
Placebo
Somnolence
30
10
Dizziness
28
14
Vision problems 28
9
Unsteadiness
21
7
Speech problems 17
3
Psychomotor slowing 17
2
"Pins and needles" 15
3
Nervousness
16
8
Nausea
12
6
Memory problems 12
3
Tremor
11
6
Confusion
10
6
Side-effects
are most noticeable the few days after an increase in dose and
then often
fade.
14. Which
side-effects are severe enough to force people to discontinue
topiramate?
The side-effects
that most frequently caused people to discontinue therapy
with topiramate
were: psychomotor slowing (4.1%), memory problems (
(3.3%),
fatigue (3.3%), confusion (3.2%), and somnolence (3.2%).
15. Does
topiramate have any psychiatric side effects?
Among the
reported side effects of topiramate are sedation, psychomotor
slowing,
agitation, anxiety, concentration problems, forgetfulness, confusion,
depression,
and depersonalization. As with other anticonvulsants, psychosis
has rarely
been reported as a side-effect.
16. How
does topiramate interact with prescription and over-the-counter
medications?
Only a few
interactions between topiramate and other drugs have been
identified.
Topiramate may increase the plasma level of phenytoin (Dilantin).
Phenytoin
lowers the concentration of topiramate in the blood by about 50%.
While topiramate
has little effect on the plasma level of carbamazepine, the
latter
may decrease the plasma level of topiramate by about 50%. Valproate
lowers
the plasma level of topiramate by about 15%. Topiramate may lead to
decreased
effectiveness of some oral anticontraceptives.
Interactions
with other prescription and over-the-counter drugs are not
known at
this time.
17. Is there
an interaction between topiramate and alcohol?
Alcohol
may increase the severity of the side-effects of topiramate.
18. Is topiramate
safe for a woman who is about to become pregnant, pregnant
or nursing
an infant?
Topiramate
is has been placed in the FDA pregnancy Category C:
"Animal
studies have shown an adverse effect on the fetus but there are no
adequate
studies in humans; The benefits from the use of the drug in pregnant
women may
be acceptable despite its potential risks . . . ."
19. Is topiramate
safe for children and adolescents?
The FDA
has recently approved the use of topiramate in children.
20. Can
topiramate be used in elderly people?
Older people
seem to handle topiramate similarly to younger ones. There is
little
experience using topiramate for the treatment of psychiatric disorders
in
the elderly.
21. Do symptoms
develop if topiramate is suddenly discontinued?
There are
no specific symptoms that have been described following the abrupt
discontinuation
of topiramate, other than the seizures that sometimes follow
the rapid
discontinuation of any anticonvulsant. Only when necessary because
of a serious
side effect, should topiramate be suddenly discontinued.
22. Is topiramate
toxic if taken in overdose?
There is
only limited data on the effects of overdoses of topiramate. There
have been
no reports of deaths following an overdose.
23. Can
topiramate be taken along with MAO inhibitors?
Yes, the
combination has been used without any special problems.
24. What
does topiramate cost?
As of 5
November1999, an on-line pharmacy (Planet Rx) was selling
topiramate
for the following amounts per tablet (when bought in lots of 100
tablets):
25 mg - $1.15
100 mg - $2.61
200 mg - $2.86
25. Might
topiramate be effective in people who have failed to receive benefit
from other
psychopharmacologic agents?
The major
use of topiramate in psychiatry is with people who have mood
disorders
that have not been adequately controlled by other medications at
times including
lamotrigine and gabapentin. A developing use is for people
with PTSD.
26. What
are the advantages of topiramate?
Topiramate
seems to be effective in some people with bipolar mood disorders
that have
not responded to lithium and/or other mood-stabilizers. Some
people
who have not been able to tolerate any antidepressant because of
switches
to mania or increased speed or intensity of cycling, or because of the
development
of mixed states, have been able to tolerate therapeutic doses of
anti- depressants
when taking topiramate.
For most
people, topiramate has tolerable side effects and it can be taken
twice a
day.
The weight
loss that accompanies topiramate therapy in some instances is
useful
for those individuals who have gained weight while taking other mood
stabilizing
drugs. In some studies 20-50% of people taking topiramate lost
weight.
27. What
are the disadvantages of topiramate?
As topiramate
has only been available for a relatively short time, it was first
marketed
in 1996, there is no information about long term side-effects. As its
use with
people with mood disorders started even more recently, it is not
known if
people who initially do well on topiramate continue to do so after
many years
of treatment.
Topiramate
increases the probability of kidney stones. the development of
kidney
stones may be prevented by increasing one's intake of water.
28. Why
should physicians prescribe, and patients take, topiramate, when there
are mood
regulating medications that have been available for many years and
which have
been shown to be effective in double-blind placebo- controlled
studies?
There are
two major reasons why physicians prescribe and patients take
topiramate
rather than conventional, better established drugs. They are that
not everyone
benefits from treatment with the older, better known drugs, and
that some
patients find the side effects of the established drugs to be
unacceptable.
As there
has not been a good psychopharmacologic treatment for people with
PTSD, topiramate
offers such people the possibility of medically -induced
relief.
29. Is topiramate
available in countries other than the USA?
Topiramate
is available in countries in South America, and Europe.
30. Has
anything been published on the use of topiramate as a therapeutic agent
for people
with mood disorders?
While reports
on the use of topiramate as a treatment for people with mood
disorders
and PTSD have been presented at various psychiatric meetings, little
is in print
about the psychiatric uses of this medication. The following
publications
are relevant to the psychiatric uses of topiramate::
Berlant
J
Poster,
presented at 39th Annual Meeting New Clinical Drug Evaluation
Program
(NIMH) Boca Raton, Florida, June 1-4, 1999.
Open-lable
topiramate treatment of post-traumatic stress disorder.
Calabrese
JR, van Kammen DP, Shelton MD, et al
American
Psychiatric Association Annual Meeting 1999, New Research
Abstracts
NR680
Topiramate
in severe treatment-refractory mania.
Gordon A,
Price LH
American
Journal of Psychiatry 1999, 156, 968-969.
Mood stabilization
and weight loss with topiramate.
Kahn A,
Faught E, Gelliam F. et al.
Seizure
1999, 8, 235-237.
Acute psychotic
symptoms induced by topiramate.
Ketter TA
et al.
Neurology
1999, 53, (5, Suppl 2), S53-S67.
Positive
and negative psychiatric effects of antiepileptic drugs in patients with
seizure
disorders.
Kusumakar
V, Yatham LN, O'Donovan CA, et al
American
Psychiatric Association Annual Meeting 1999, New Research
Abstracts
NR477
Topiramate
in rapid-cycling bipolar women.
Marcotte
D
Journal
of Affective Disorders 1998, 50, 245-251.
Use of
topiramate, a new anti-epileptic as a mood stabilizer.
Martin R,
Kuzniecky R, Ho S, et al.
Neurology,
1999, 15, 321-327.
Cognitive
side effects of topiramate, gabapentin, and lamotrigine in healthy
young adults.
Walden J,
Hesslinger B
Fortschr
Neurol Psychiat 1996, 63, 320-335.
Value of
old and new anticonvulsants in treatment of psychiatric diseases.
Post RM
Schizophrenia Research 1999, 39, 153-158. Comparative
pharmacology
or bipolar disorder and schizophrenia.
Post RM,
Frye MA, Denicoff KD, et al.
Neuropsychopharmacology
1998 Sep;19(3):206-219
Beyond
lithium in the treatment of bipolar illness.
31. Additions
and corrections?
Please address
additions and corrections to:
Ivan K.
Goldberg, M.D.
1556 Third
Avenue
New York,
NY 10128-3100
Voice:
+1-212 876 7800
120 N. Main
Street
New City,
NY 10956
Voice:
+1-914-216-8192
Email Psydoc@PsyCom.Net
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