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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