- 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
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.
Topamax for Weight loss
Topiramate (Topamax) is used "off-label" as a weight loss pill. This drug has been examined in numerous high quality clinical studies specifically for the treatment of obesity, including several studies investigated obese patients with type 2 diabetes and hypertension. The evidence of a strong weight-reducing potential of is indisputable and clinically significant. Topamax treatment 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
Mean weight loss is in the range of 2 to 9 kg 18,24,25 or 3.8-11% of total body weight26.
How long will it take for topiramate for weight loss results?
Weight loss effect produced by topiramate occurs mainly within 6 months21, 24.
In clinical trials on weight loss and obesity topiramate was used at doses 96-250 mg per day.
Mechanism of action: how Topiramate causes weight loss
It is proposed that topiramate reduces body weight via following actions:
Taste impairment. Topiramate frequently causes taste perversion, making foods taste less appealing14, 19.
Loss of appetite during topiramate treatment results in reduced food intake 15.
Reduced caloric intake 21 contributes to reduced body fat stores and body weight22.
Increased energy expenditure and decreased energetic efficiency 23 - there is evidence from animal studies that topiramate may enhance thermogenesis.
Reduction in leptin, corticosteroid, and neuropeptide-Y concentrations 20 are important factors in weight loss during topiramate treatment and may explain continuing weight loss effect after drug discontinuation18.
Improves insulin sensitivity and reduces blood glucose levels -- insulin-sensitizing and blood glucose-normalizing effects may also encourage anti-obesity effects.
Qsymia® ( Phentermine/Topiramate): new weight-loss pill
The combination of phentermine and topiramate produces 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 appears to provide additional health benefits, including significant improvements in blood
pressure, blood sugar measurements (hemoglobin A1C), cholesterol, and triglycerides.
Initially, phentermine/topiramate combo is was 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.
Qsymia® (phentermine/topiramate) is available in 4 doses: 3.75 mg/23 mg; 7.5 mg/46 mg; 11.25 mg/69 mg; and 15 mg/92 mg.
- 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).
- Proven weight loss and appetite suppression potential 4. The combination of phentermine/topiramate (Qsymia®) is officially indicated for weight management.
- Can reverse weight gain induced by psychotropic drugs 5
- Relatively low drug interaction potential
- Risk of developing kidney stones (about 1.5%)
- Risk of acute myopia and angle-closure glaucoma
- Decrease efficacy of oral contraceptives
- High rate of side effects related to the central or peripheral nervous system, including paresthesia (sensation of numbness or tingling), difficulty with memory, concentration, and attention
- The FDA has dropped topiramate's pregnancy category from Category C to Category D -- risk of oral clefts in infants exposed to topiramate during pregnancy 16.
- chronic daily headache
- 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
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.
Evaluations and Reviews from Patients
- 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.
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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.
- 7. Johnson BA, Ait-Daoud N, Akhtar FZ,
Ma JZ Arch Gen Psychiatry. 2004 Sep;61(9):905-12.
- 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.
- 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
- 16. Andrea V. Margulis, Allen A. Mitchell, Suzanne M. Gilboa, Martha M. Werler, Murray A. Mittleman, Robert J. Glynn, Sonia Hernandez-Diaz, National Birth Defects Prevention Study. Use of topiramate in pregnancy and risk of oral clefts. American Journal of Obstetrics & Gynecology. November 2012
- 17. Johnson BA, Rosenthal N, Capece JA, et al. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA. 2007 Oct 10;298(14):1641-51.
- 18. Liang CS, Yang FW, Huang SY, Ho PS. Continuing weight-loss effect after topiramate discontinuation in obese persons with schizophrenia: a pilot open-label study. Pharmacopsychiatry. 2014 Jul;47(4-5):162-8.
- 19. Johnson BA, Rosenthal N, Capece JA, et al. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA. 2007 Oct 10;298(14):1641-51. PubMed
- 20. Ozcelik AA, Serdaroglu A, Bideci A, Arhan E, Soysal Ş, Demir E, Gücüyener K. The effect of topiramate on body weight and ghrelin, leptin, and neuropeptide-Y levels of prepubertal children with epilepsy. Pediatr Neurol. 2014 Aug;51(2):220-4.
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- 25. Moradi S, Kerman SR, Mollabashi M. The effect of topiramate on weight loss in patients with type 2 diabetes. J Res Med Sci. 2013 Apr;18(4):297-302.
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- 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.