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Topamax

Topamax (Topiramate)


  • Generic name: Topiramate
  • Trade names: Topamax, Trokendi XR
  • Dosages: Capsules, sprinkle 15 mg, 25 mg; Tablets 25 mg, 50 mg, 100 mg
  • Pharmacologic category: Anticonvulsant
  • FDA approved: 24 December 1996
  • Manufacturer: Ortho-McNeil Neurologics
Medical uses

Topamax (Topiramate) is used as monotherapy or adjunctive therapy for partial onset seizures and primary generalized tonic-clonic seizures; adjunctive therapy for seizures associated with Lennox-Gastaut syndrome; prophylaxis of migraine headache.

Some doctors prescribe Topamax as a mood stabilizer for people with bipolar disorder (manic depression).

Latest Research: New Weight-Loss Cocktail

The mix of phentermine and topiramate produced significant weight loss (up to 10%) in obese people over the course of one year, according to researchers at Duke University Medical Center15. Phentermine/topiramate mix appears to provide additional health benefits, including significant improvements in blood pressure, blood sugar measurements (hemoglobin A1C), cholesterol, and triglycerides.

Phentermine/topiramate combo is being developed under the trade name Qnexa by Vivus, a California pharmaceutical company.

In October 2010, the FDA advisory committee voted 10-6 against approval of the phentermine-topiramate combination for weight loss. The panel members and the agency agreed that the combination was effective. The FDA turned down Qnexa's application due to safety concerns: increase in heart rate (an average of about one extra beat per minute), adverse psychological events, impaired memory and concentration, and teratogenicity.

In July 2012, the FDA approved Qsymia (phentermine and topiramate extended-release) as an adjunct to diet and exercise in obese patients with a body mass index (BMI) of 30 or more or overweight patients with a BMI of 27 who have at least one weight-related comorbidity, such as hypertension, type 2 diabetes, or dyslipidemia.

Pharmacological characteristics
  • Absorption: Topiramate absorption is rapid, not affected by food. T max is 2 hr. Steady state is reached in about 4 days.
  • Elimination half-life: 21 hr.
  • Metabolism: Hepatic via P450 enzymes.
  • Excretion: Topiramate is primarily eliminated unchanged in urine (about 70% of a dose).
Advantages
  • weight loss and appetite suppression potential 4
  • can reverse weight gain induced by psychotropic drugs 5
  • probably works for all seizure types
  • relatively low drug interaction potential
  • one of the few FDA-approved prescriptions for migraine prevention
Disadvantages
  • risk of developing kidney stones (about 1.5%)
  • risk of acute myopia and angle-closure glaucoma
  • decrease efficacy of oral contraceptives
  • more emotional and cognitive complaints than with other newer anticonvulsants
Unlabeled uses
  • chronic daily headache 2
  • cluster headache 9
  • neuropathic pain 12
  • bipolar disorder 6
  • obesity and weight loss 4, 14
  • alcohol dependence 7
  • opiate withdrawal 13
  • bulimia nervosa 8
  • smoking cessation 10
  • binge eating disorder 11

Topamax for Headaches
The study has shown that Topamax may decrease the number of the headache days per week, significantly decrease the headache severity, reduce the headache hours per day and weekly analgesic consumption. These benefits continued for an average follow-up of 8+/-4 months. The average effective dose was 100 mg/day. Slowly increasing topiramate at moderate increments resulted in high tolerability 2.

Topamax is also safe, well tolerated, and highly effective at low doses for chronic daily headaches in children 3.

Topamax for Weight loss
The evidence of a strong weight-reducing potential of Topamax is indisputable and clinically significant. Topamax often results in a significant weight reduction which appears to be one of the most attractive consequences of the therapy. For overweight people, this may be a good thing. However, for some people weight loss may be a highly undesirable (for example, for growing children).

Topamax is not FDA approved for weight loss, but many clinical studies have demonstrated it's weight reducing potential.

In long-term clinical study at 60 weeks, patients in the placebo group lost 1.7% of their baseline weight, while patients in the Topamax 96, 192, and 256 mg/day groups lost 7.0, 9.1, and 9.7%, respectively. Weight loss >/=5% of baseline weight was achieved by 18% of subjects in the placebo arm vs 54, 61, and 67% of patients receiving topiramate 96, 192, and 256 mg/day, respectively. Weight loss >/=10% was achieved by 6 vs 29, 40, and 44%, respectively. Weight loss was accompanied by significant improvements in blood pressure and glucose and insulin. The most common adverse events more frequently observed in topiramate-treated patients occurred mostly during the titration phase and were related to the central or peripheral nervous system and included paresthesia, difficulty with concentration and attention, difficulty with memory, language problems, nervousness, and psychomotor slowing. 14

It is proposed that Topamax contributes to drops in body weight via energy expenditure elevations; reduced caloric intake and the activity of salivary enzymes; reduction in leptin and corticosteroid concentrations; and reduction in serum glucose and insulin concentrations.

Mechanism of action

Anticonvulsant activity may be due to a combination of potential mechanisms: blocks neuronal voltage-dependent sodium channels, enhances GABA(A) activity, antagonizes AMPA/kainate glutamate receptors, and weakly inhibits carbonic anhydrase.

Discussions Boards & Forums

If you are going to buy Topamax or Topiramate without having a prescription, it may be a good idea to read users reviews first.

References
  • 1. Topamax Prescription
  • 2. Mosek A, Dano M. Topiramate in refractory chronic daily headache. An open trial. J Headache Pain. 2005 Apr;6(2):77-80.
  • 3. Borzy JC, Koch TK, Schimschock JR. Effectiveness of topiramate in pediatric chronic daily headache. Pediatr Neurol. 2005 Nov;33(5):314-6.
  • 4. Chengappa KN, Chalasani L, Brar JS, Parepally H, Houck P, Levine J. Changes in body weight and body mass index among psychiatric patients receiving lithium, valproate, or topiramate: an open-label, nonrandomized chart review. Clin Ther. 2002 Oct;24(10):1576-84.
  • 5. Van Gaal L, Rissanen A, Wilding J, Vercruysse F, Perry B, Fitchet M. Efficacy and safety of topiramate in obese subjects. Int J Obes. 2003;27:(suppl1):S14.
  • 6. Vieta E, Torrent C, Garcia-Ribas G, Gilabert A, Garcia-Pare's G, Rodriguez A, Cadevall J, Garci'a-Castrillo'n J, Lusilla P, Arrufat F. Use of topiramate in bipolar disorders. J Clin Psychopharmacol. 2002 Aug;22(4):431-5. PubMed
  • 7. Johnson BA, Ait-Daoud N, Akhtar FZ, Ma JZ Arch Gen Psychiatry. 2004 Sep;61(9):905-12. PubMed
  • 8. Hedges DW, Reimherr FW, Hoopes SP, Rosenthal NR, Kamin M, Karim R, Capece JA. Topiramate in bulimia nervosa: a randomized, double-blind, placebo-controlled trial, part 2: improvement in psychiatric measures. J Clin Psychiatry. 2003 Dec;64(12):1449-54. PubMed
  • 9. Lainez MJ, Pascual J, Pascual AM, Santonja JM, Ponz A, Salvador A. Topiramate in the prophylaxis of cluster headache. Headache. 2003 Jul-Aug;43(7):784-9 PubMed
  • 10. Khazaal Y, Cornuz J, Bilancioni R, Zullino DF. Topiramate for smoking cessation. Psychiatry Clin Neurosci. 2006 Jun;60(3):384-8.
  • 11. McElroy SL, Shapira NA, Arnold LM, Keck PE, Rosenthal NR, Wu SC, Capece JA, Fazzio L, Hudson JI. Long-term use of topiramate in the binge-eating disorder associated with obesity. J Clin Psychiatry. 2004 Nov;65(11):1463-9. PubMed
  • 12. Chong MS, Libretto SE. The rationale and use of topiramate for treating neuropathic pain. Clin J Pain. 2003 Jan-Feb;19(1):59-68. PubMed
  • 13. Zullino DF, Krenz S, Zimmerman G, Miozzari A, Rajeswaran R, Kolly S, Khazaal Y. Subst Abus. 2005 Dec;25(4):27-33. PubMed
  • 14. Wilding J, Van Gaal L, Rissanen A, Vercruysse F, Fitchet M; OBES-002 Study Group. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of Topamax in obese subjects. Int J Obes Relat Metab Disord. 2004 Nov;28(11):1399-410.
  • 15. Gadde KM, Allison DB, Ryan DH, Peterson CA, Troupin B, Schwiers ML, Day WW. Effects of phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011 Apr 16;377(9774):1341-52. PubMed

Last updated: December 2013

Interesting facts

Topamax
  • Topiramate is a sulfamate-substituted monosaccharide, related to fructose, a rather unusual chemical structure for an anticonvulsant.
  • Topamax was originally developed as an oral hypoglycaemic agent afterward approved as anticonvulsant.

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