FAQ: Topiramate (Topamax), Mood Disorders and PTSD.

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

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