NOTE: Topiramate is only approved for the

treatment of people with seizures. There are

few systematic studies that establish the safety

or efficacy of topiramate as a treatment

for people with mood disorders, PTSD, or eating disorders While such studies are underway, what

is currently known about the use of topiramate

for the control of mood disorders, PTSD and eating

disorders comes mostly 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.

Topiramate has also been successfully used to decrease binge eating and
overeating that is caused by other psychiatric medications.


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%).

Much less frequently happening but more serious side-effects
that force people to stop topiramate therapy include kidney
stones, which affect about 1% of people taking the drug, and
acute glaucoma, which to date had been reported in about one
person in 35,000 taking topiramate. The sudden onset
of back pain may indicate the presence of a kidney
stone, while eye pain, changes in vision or the develpment
of redness in the eye may indicate glaucoma. Most cases of
glaucoma have developed within the first two months of therapy
with topiramate.


Information from the FDA on topiramate and glaucoma.


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 3 April 2005, an on-line pharmacy (Drugstore.com)
was selling topiramate for the following amounts
per tablet (when bought in lots of 100 tablets):


25 mg – $1.45

100 mg – $3.73

200 mg – $5.75




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.

Topiramate has also been shown to decrease craving for alcohol
in people with alcoholism, and to prevent migraine headaches.


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 many countries throughout the world.


30. Has anything been published on the use of topiramate
as a therapeutic agent for people with mood disorders and/or PTSD?

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:

Alao AO, Dewan MJ.

Journal of Nervous and Mental Disease, 2001,189, 60-63.



Evaluating the tolerability of the newer mood stabilizers.

[No MEDLINE abstract available]


American Journal of Ophthalmology 2001, 132, 112-114



Presumed topiramate-induced bilateral acute angle-closure glaucoma.


[MEDLINE abstract]

Andrade C.

Bipolar Disorders, 2001, 3,211-212.



Confusion and dysphoria with low-dose topiramate in a patient with bipolar
disorder.



[MEDLINE abstract]

Barbee JG.

International Journal of Eating Disorders, 2003, 33, 468-472.
Topiramate in the treatment of severe bulimia nervosa with comorbid mood disorders: A
case series.

[MEDLINE abstract]

Berlant JL.

Journal of Clinical Psychiatry 2001, 62 (Suppl 17), 60-63.



Topiramate in posttraumatic stress disorder: preliminary clinical
observations.



[MEDLINE abstract]

Berlant J.

Poster, presented at 39th Annual Meeting New Clinical Drug Evaluation
Program (NIMH) Boca Raton, Florida, June 1-4, 1999.



Open-label topiramate treatment of post-traumatic stress disorder.


[Read a report on this presentation]

Berlant J.

Journal of Clinical Psychiatry 2002, 63, 15-20.



Open-label topiramate as primary or adjunctive therapy in chronic civilian
posttraumatic stress disorder: a preliminary report.



[MEDLINE abstract]

Besag FM.

Drug Safety 2001, 24, 513-536.



Behavioral effects of the new anticonvulsants.


[MEDLINE abstract]

Bowden CL.

Expert Opin Investig Drugs. 2001, 10, 661-671.



Novel treatments for bipolar disorder.


[MEDLINE abstract]

Brandes JL, Saper JR, Diamond M, et al.

Journal of the American Medical Association, 2004, 291,965-973.



Topiramate for migraine prevention: A randomized controlled trial.


[MEDLINE abstract]

Calabrese JR, Keck PE Jr, McElroy SL, Shelton MD.

Journal of Clinical Psychopharmacology 2001, 21, 340-342.



A pilot study of topiramate as monotherapy in the treatment of acute
mania.



[MEDLINE abstract]

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.

[No MEDLINE abstract available]


[MEDLINE abstract]

Calabrese JR, Shelton MD, Rapport DJ, Kimmel SE.

Journal of Clinical Psychiatry 2002, 63 (Suppl 3),5-9.



Bipolar disorders and the effectiveness of novel anticonvulsants.

Carpenter LL, Leon Z, Yasmin S, Price LH

Journal of Affective Disorders 2002 May; 69, 251-255.



Do obese depressed patients respond to topiramate? a retrospective chart
review.



[MEDLINE abstract]

Cassano P, Lattanzi L, Pini S, et al.

Bipolar Disorders 2001, 3, 161.



Topiramate for self-mutilation in a patient with borderline personality
disorder.


[No MEDLINE abstract available]

Chengappa K N, Gershon S, Levine J.

Bipolar Disorders 2001, 3,215-232



The evolving role of topiramate among other mood stabilizers in the
management of
bipolar disorder.



[MEDLINE abstract

Chengappa KN, Rathore D, Levine J, et al.

Bipolar Disorder. 1999 Sep;1(1):42-53.



Topiramate as add-on treatment for patients with bipolar mania.


[MEDLINE Abstract]

Chengappa KN, Levine J, Rathore D, Parepally H, Atzert R.

European Psychiatry 2001, 16, 186-190.



Long-term effects of topiramate on bipolar mood instability, weight
change and
glycemic control: a case-series.



[MEDLINE abstract]

Colom F, Vieta E, Benaberra A, et al

Journal of Clinical Psychiatry 2001, 62, 475-476.



Topiramate abuse in a bipolar patient with an eating disorder.


[MEDLINE abstract]

Davanzo P, Cantwell E, Kleiner J, et al.

Journal of the American Academy of Child and Adolescent Psychiatry 2001,
40, 262-263.



Cognitive changes during topiramate therapy.

[No MEDLINE abstract available]

De Leon OA.

Harvard Review of Psychiatry. 2001, 9, 209-222.



Antiepileptic drugs for the acute and maintenance treatment of bipolar
disorder.



[MEDLINE abstract]

DelBello MP, Kowatch RA, Warner J, et al.

Journal of Child and Adolescent Psychopharmacology, 2002, 12, 323-330.



Adjunctive topiramate treatment for pediatric bipolar disorder: a retrospective
chart review.



[MEDLINE abstract]

Deutsch SI, Schwartz BL, Rosse RB, et al.

Clinical Neuropharmacology, 2003, 26, 199-206.



Adjuvant topiramate administration: a pharmacologic strategy for addressing NMDA
receptor hypofunction in schizophrenia.



[MEDLINE abstract]

Doan RJ, Clendenning M.

Canadian Journal of Psychiatry 2000, 45, 937-938.



Topiramate and hepatotoxicity.

[No MEDLINE abstract available]

Drapalski AL, Rosse RB, Peebles RR, Schwartz BL, Marvel CL, Deutsch SI.

Clinical Neuropharmacology 2001, 24, 290-294.



Topiramate improves deficit symptoms in a patient with schizophrenia
when added
to a stable regimen of antipsychotic medication.



[MEDLINE abstract

Dursun SM, Deakin JF.

Journal of Psychopharmacology, 2001, 15, 297-301.



Augmenting antipsychotic treatment with lamotrigine or topiramate in
patients with
treatment-resistant schizophrenia: A naturalistic case-series outcome
study.



[MEDLINE Abstract]

Dursun SM, Devarajan S.

Canadian Journal of Psychiatry 2001, 46, 287-288.



Accelerated weight loss after treating refractory depression with
fluoxetine
plus topiramate: possible mechanisms of action?


[No MEDLINE abstract available]

Erfurth A, Kuhn G.

Neuropsychobiology 2000, 42 (Suppl 1), 50-51.



Topiramate monotherapy in the maintenance treatment of bipolar I disorder:
Effects on mood, weight and serum lipids.



[MEDLINE abstract

Felstrom A, Blackshaw S.

American Journal of Psychiatry, 2002, 159, 1246-1247 .



Topiramate for bulimia nervosa with bipolar II disorder.
[No MEDLINE abstract available]

Gareri P, Falconi U, de Fazio P et al.

Progress in Neurobiology 2000, 61, 353-396.



Conventional and new antidepressants drugs in the elderly.


[MEDLINE abstract]

Ghaemi SN, Manwani SG, Katzow JJ, et al.

Annals of Clinical Psychiatry 2001, 13, :185-189.



Topiramate treatment of bipolar spectrum disorders: A retrospective chart
review.



[MEDLINE abstract]

Gitlin MJ.

Bulletin of the Menninger Clinic 2001 65, 26-40.



Treatment-resistant bipolar disorder.


[MEDLINE abstract]


Goldberg JF, Burdick KE.

Journal of Clinical Psychiatry 2001, 62 Suppl 14, 27-33.



Cognitive side effects of anticonvulsants.


[MEDLINE abstract]

Gordon A, Price LH

American Journal of Psychiatry 1999, 156, 968-969.



Mood stabilization and weight loss with topiramate.

[No MEDLINE abstract available]

Grunze HC, Normann C, Langosh J et al.

Journal of Clinical Psychiatry 2001,62, 464-468.



Antimanic efficacy of topiramate in 11 patients in an open trial
with an on-off-on design.



[MEDLINE abstract]

Guerdjikova AI, Kotwal R, McElroy SL.

Obesity Surgery, 2005, 15, 273-277.



Response of recurrent binge eating and weight gain to topiramate in patients
with binge eating disorder after bariatric surgery.



[MEDLINE abstract]

Jochum T, Bar KJ, Sauer H.

J Neurology Neurosurgery and Psychiatry, 2002, 73, 208-209



Topiramate induced manic episode.

[No MEDLINE abstract available]

Khan A, Faught E, Gelliam F. et al.

Seizure 1999, 8, 235-237.



Acute psychotic symptoms induced by topiramate.


[MEDLINE abstract]

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.



[MEDLINE abstract]

Ketter TA et al.

Cellular and Molecular Neurobiology, 1999, 19, 511-532.



Metabolism and excretion of mood stabilizers and new anticonvulsants.



[MEDLINE abstract]

Klufas A, Thompson D.

American Journal of Psychiatry. 2001, 158, 1736.



Topiramate-induced depression.

[No MEDLINE abstract available]

Komanduri R.

Journal of Clinical Psychiatry, 2003, 64, 612.



Two cases of alcohol craving curbed by topiramate.

[No MEDLINE abstract available]

Kupka RW, Nolen WA, Altshuler LL et al.

British Journal of Psychiatry, Supplement 2001, 41, s177-s183.



The Stanley Foundation Bipolar Network. 2. Preliminary summary of
demographics, course of illness and response to novel treatments.



[MEDLINE abstract]

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.

[No MEDLINE abstract available]

Letmaier M, Schreinzer D, Wolf R, Kasper S.

International Clinical Psychopharmacology. 2001, 16, 295-298.



Topiramate as a mood stabilizer.


[MEDLINE abstract]

Li X, Ketter TA, Frye MA

Journal of Affective Disorders 2002, May;69, 1-14.



Synaptic, intracellular, and neuroprotective mechanisms of anticonvulsants:
are they relevant for the treatment
and course of bipolar disorders?



[MEDLINE abstract]



McElroy SL, Suppes T, Keck PE, et al

Biological Psychiatry, 2000, 47, 1025-1033.



Open-label adjunctive topiramate in the treatment of bipolar disorders.



[MEDLINE abstract]

McIntyre RS, Mancini DA, McCann S, Srinivasan J, Sagman D, Kennedy SH.

Bipolar Disorders. 2002, 4, 207-213.



Topiramate versus bupropion SR when added to mood stabilizer therapy for the
depressive phase of bipolar disorder: a preliminary single-blind study.



[MEDLINE abstract]



Maidment ID

Annals of Pharmacotherapy, 2002, 36(7):1277-1281 .



The use of topiramate in mood stabilization.


[MEDLINE abstract

>
Marcotte D

Journal of Affective Disorders 1998, 50, 245-251.



Use of topiramate, a new anti-epileptic as a mood stabilizer.


[MEDLINE abstract]

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.



[MEDLINE abstract]

Millson RC, Owen JA, Lorberg GW, Tackaberry L.

American Journal of Psychiatry 2002, 159, 675.



Topiramate for refractory schizophrenia.

[No MEDLINE abstract available]

Normann C, Langosch J, Schaerer LO et al.

American Journal of Psychiatry, 1999, 156, 2014.



Treatment of acute mania with topiramate.

[No MEDLINE abstract available]

Pavuluri MN, Janicak PG, Carbray J.

Journal of Child and Adolescent Psychopharmacology, 2002, 12, 271-273.



Topiramate plus risperidone for controlling weight gain and
symptoms in preschool mania.


[No MEDLINE abstract available]

Pecuch PW, Erfurth A.

Journal of Clinical Psychopharmacology 2001 21, 243-244.



Topiramate in the treatment of acute mania.

[ No MEDLINE abstract available]

Pinninti NR, Zelinski G.
Journal of Clinical Psychopharmacology, 2002, 22, 340 .



Does topiramate elevate serum lithium levels?

[No MEDLINE abstract available]

Post RM

Schizophrenia Research 1999, 39, 153-158.



Comparative pharmacology or bipolar disorder and schizophrenia.


[MEDLINE abstract]

Post RM, Frye MA, Denicoff KD, et al.

Neuropsychopharmacology 1998 Sep;19(3):206-219



Beyond lithium in the treatment of bipolar illness.


[MEDLINE abstract]

Post RM, Frye MA, Denicoff KD et al.

Bipolar Disorders 2000, 2, 305-315.
Emerging trends in the treatment of rapid cycling bipolar disorder: a selected
review.



[MEDLINE abstract]

Schlatter FJ, Soutullo CA, Cervera-Enguix S.

Journal of Clinical Psychopharmacology 2001 21, 464-466.



First break of mania associated with topiramate treatment.

[No MEDLINE abstract available]

Tondo L, Hennen J, Baldessarini RJ.

Acta Psychiatrica Scandinavica, 2003, 108, 4-14.



Rapid-cycling bipolar disorder: effects of long-term treatments.


[MEDLINE abstract]

Vieta E, Gilabert A, Rodriguez A, et al.

Actas Esp Psiquiatr 2001, 29, 148-152.



Effectiveness and safety of topiramate in treatment-resistant bipolar disorder



[MEDLINE abstract]

Vieta E, Goikolea JM, OLivares JM, et al.

Journal of Clinical Psychiatry, 2003, 64, 834-839.



1-year follow-up of patients treated with risperidone and topiramate for a manic
episode.


Vieta E, Sanchez-Moreno J, Goikolea JM, et al.

World Journal of Biological Psychiatry, 2003, 4, :172-176.>/I>

Adjunctive Topiramate in Bipolar II Disorder.


[MEDLINE abstract]

Vieta E, Torrent C, Garcia-Ribas G, Gilabert A, et al.

Journal of Clinical Psychopharmacology, 2002, 22, 431-435



Use of topiramate in treatment-resistant bipolar spectrum disorders.


[MEDLINE abstract]

Winkelman JW.

Sleep Medicine, 2003, 4, 243-266.

Treatment of nocturnal eating syndrome and sleep-related eating disorder with
topiramate.



[MEDLINE abstract]

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

Fax: +1-212-876-7821

Email Psydoc@PsyCom.Net