Topiramate (Topamax) versus ...

Topiramate vs. Divalproex sodium (Depakote)

Both anticonvulsants topiramate and divalproex sodium have been FDA approved for prophylaxis of migraine headaches and are recommend as first-line agents for migraine prevention.

Despite their proven efficacy in migraine prevention, there are no head-to-head randomized studies comparing topiramate and divalproex sodium. According to the open-label nonrandomized investigation topiramate and divalproex have quite similar effectiveness, but differ in their side effects profile 6.

Results of prospective "real-world" study of topiramate vs divalproex sodium in the preventive treatment of migraine 6 Topiramate Divalproex sodium
Reduction in headache frequency of >50% at 3 months
40 patients of 69
26 patients of 51
Most common side effects
(% of patients who completed the study)
weight loss (50%),
paresthesia (48%),
cognitive disturbances (20%)
weight gain (24%),
hair loss (24%),
gastrointestinal symptoms (24%)

Note: Both Topiramate and Divalproex are pregnancy category D (teratogenic drugs).

Topiramate vs. Carbamazepine (Tegretol)


Both agents have similar effectiveness for initial treatment of newly diagnosed epilepsy: time to exit, time to first seizure, and the proportion of patients seizure-free during the last 6 months of treatment 2.

In the open randomised trial comparing monotherapy with topiramate versus carbamazepine the percentage of free seizure patients was greater in topiramate group than carbamazepine 4.

Side effects and tolerability: Topiramate is associated with the fewest discontinuations due to adverse events 2.

Most common adverse events associated with topiramate are somnolence, weight loss and with carbamazepine are somnolence, dizziness and seizure discontrol 4.

Topiramate vs. Valproate (Depacon, Depakene)


Both anticonvulsants have similar effectiveness for initial treatment of newly diagnosed epilepsy: time to exit, time to first seizure, and the proportion of patients seizure-free during the last 6 months of treatment 2.

Results of randomized open-label observational study comparing topiramate and valproate in juvenile myoclonic epilepsy 10 Topiramate Valproate
Patients free of myoclonic seizures for 24 weeks
7 patients of 11
9 patients of 16
Adverse effects severity of adverse effects was favourable for topiramate
Conclusion: valproate may be replaced with topiramate, especially for the patients with juvenile myoclonic epilepsy who do not tolerate valproate.

Migraine prophylaxis

Topiramate appears to be equivalent in efficacy and safety to sodium valporate. Both agents cause significant decrease in duration, monthly frequency, and intensity of headache 5.

Results of 24-week, randomized, double-blind, crossover, trial of topiramate and sodium valporate in migraine prevention 5 Topiramate Valproate
Regimen 25 mg daily increment over 1 week to 50 mg for a total of 2 months. 200 mg daily increment over 1 week to 400 mg for 2 months
Monthly migraine frequency decrease, episode per month from 5.4 to 3.2 from 5.4 to 4.0
Headache intensity decrease by visual analog scale (VAS) from 6.9 to 3.7 from 7.7 to 5.8
Headache duration decrease, hours from 17.3 to 3.9 from 21.3 to 12.3

Topiramate vs. Fluvoxamine

Pathological gambling

In the comparison study of the effectiveness of topiramate versus fluvoxamine in the treatment of PG the CGI-improvement (Clinical Global Impression-Improvement) score was significantly better for the topiramate group 3.

Topiramate vs. Amitriptyline


Topiramate is at least as effective as amitriptyline in reducing the frequency of migraines. Topiramate promotes weight loss and improves weight satisfaction, whereas amitriptyline often contributes to weight gain.

The study7 examined the prophylactic efficacy of combined amitriptyline and topiramate in patients with 3-12 migraine episodes, compared with that of monotherapy with each drug. All treatments resulted in significant improvement in all efficacy measures.

The long-term, multicenter, randomized, double-blind, double-dummy, parallel-group, non-inferiority comparative study8 of topiramate versus amitriptyline in migraine prevention found that topiramate was associated with improvement in some quality-of-life indicators compared with amitriptyline and was associated with weight loss and improved weight satisfaction.

Results of randomized, double-blind, trial of topiramate versus amitriptyline in migraine prevention 8 Topiramate Amitriptyline
The least squares mean change from baseline in the mean monthly number of migraine episodes
Secondary outcome measures
no significant differences
Functional disability scores during migraine attacks
significantly greater improvement
Weight change mean weight loss of 2.4 kg mean weight gain of 2.4 kg
Treatment-emergent adverse events of mild or moderate severity 66.7% 66.3%
Most common adverse events paresthesia (29.9%), fatigue (16.9%), somnolence (11.9%), hypoesthesia (10.7%), and nausea (10.2%) dry mouth (35.5%), fatigue (24.3%), somnolence (17.8%), weight increase (13.6%), dizziness (10.7%), and sinusitis (10.7%)

Chronic daily headache

Topiramate is equivalent to amitriptyline in r reducing the frequency of headache in children with chronic daily headache.

In the recent study 57 children (aged 9-16 years) with chronic daily headache were randomly assigned to two groups: group A received amitriptyline and group B received topiramate9. 55% of the patients in amitriptyline group and 61% of patients in topiramate group achieved reduction of more than 50% in monthly headache frequency. There was no significant difference in responder rate or adverse event rate between the two groups. By the end of the 4-month treatment period, there were no significant differences in the final average severity and monthly frequency of headaches between treatment groups.


Topiramate vs. Flunarizine (Sibelium)

Unlike topiramate, which is an anticonvulsant, flunarizine is a calcium channel blocking agent. Flunarizine is not available in the U.S.

Results of randomized, open-label, blinded-endpoint trial of topiramate versus flunarizine in migraine prevention 11 Topiramate Flunarizine
Reduction in the numbers of headache days -2.3 -4.9
Reduction in the numbers of migraine days -1.4 -4.3
Reduction in the numbers of days of acute abortive medication use -0.2 -2.3
Reduction in the numbers of acute abortive medication tablets taken -0.5 -4.6

Further reading
  • 1. Physicians’ Desk Reference, 59th ed; Thomson PDR: Montvale, NJ; 2005.
  • 2. Privitera MD, Brodie MJ, Mattson RH, Chadwick DW, Neto W, Wang S; EPMN 105 Study Group. Topiramate, carbamazepine and valproate monotherapy: double-blind comparison in newly diagnosed epilepsy. Acta Neurol Scand. 2003 Mar;107(3):165-75. PubMed
  • 3. Dannon PN, Lowengrub K, Gonopolski Y, Musin E, Kotler M. Topiramate versus fluvoxamine in the treatment of pathological gambling: a randomized, blind-rater comparison study. Clin Neuropharmacol. 2005 Jan-Feb;28(1):6-10. PubMed
  • 4. Reséndiz-Aparicio JC1, Rodríguez-Rodríguez E, Contreras-Bernal J, Ceja-Moreno H, Barragán-Pérez E, Garza-Morales S, Malagón-Valdéz J, Ortega-González F. A randomised open trial comparing monotherapy with topiramate versus carbamazepine in the treatment of paediatric patients with recently diagnosed epilepsy. Rev Neurol. 2004 Aug 1-15;39(3):201-4. PubMed
  • 5. Shaygannejad V, Janghorbani M, Ghorbani A, Ashtary F, Zakizade N, Nasr V. Comparison of the effect of topiramate and sodium valporate in migraine prevention: a randomized blinded crossover study. Headache. 2006 Apr;46(4):642-8. PubMed
  • 6. Krymchantowski AV, Jevoux CC. Topiramate vs divalproex sodium in the preventive treatment of migraine: a prospective "real-world" study. Headache. 2011 Apr;51(4):554-8. PubMed
  • 7. Keskinbora K, Aydinli I. A double-blind randomized controlled trial of topiramate and amitriptyline either alone or in combination for the prevention of migraine. Clin Neurol Neurosurg. 2008 Dec;110(10):979-84
  • 8. Dodick DW, Freitag F, Banks J, Saper J, Xiang J, Rupnow M, Biondi D, Greenberg SJ, Hulihan J; CAPSS-277 Investigator Group. Topiramate versus amitriptyline in migraine prevention: a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority trial in adult migraineurs. Clin Ther. 2009 Mar;31(3):542-59. PubMed
  • 9. Sezer T, Kandemir H, Alehan F. A randomized trial comparing amitriptyline versus topiramate for the prophylaxis of chronic daily headache in pediatric patients. Int J Neurosci. 2013 Aug;123(8):553-6.
  • 10. Park KM, Kim SH, Nho SK, Shin KJ, Park J, Ha SY, Kim SE. A randomized open-label observational study to compare the efficacy and tolerability between topiramate and valproate in juvenile myoclonic epilepsy. J Clin Neurosci. 2013 Aug;20(8):1079-82. PubMed
  • 11. Lai KL, Niddam DM, Fuh JL, et al. Flunarizine versus topiramate for chronic migraine prophylaxis: a randomized trial. Acta Neurol Scand. 2016 Jun 16. PubMed

Published: March 31, 2008
Last updated: February 24, 2017


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