Topiramate (Topamax®) vs Divalproex (Depakote®)
Based on "Essential Psychopharmacology"
written by Stephen M. Stahl, MD, PhD
Topiramate advantages over Divalproex
- Unlike topiramate, divalproex may cause serious and potentially fatal hepatotoxicity, life-threatening pancreatitis.
- Topiramate is a preferrable choice for patients who wish to avoid weight gain as well as for patients for whom weight loss is highly desirable.
- Topiramate requires little monitoring and has a relatively favorable pharmacokinetic profile.
- No contraindications.
Divalproex advantages over Topiramate
- Valproate has a long history of use and is the best established broad-spectrum antiepileptic drug.
- Divalproex is effective for impulsivity and aggressive behavior not only in bipolar disorder but also in dementia and personality disorders.
• Trokendi® XR
• Qudexy® XR
• Depakote® ER
• Depakote® Sprinkle
|• Sulfamate-substituted monosaccharide||• Mood stabilizer
• Compound comprised of sodium valproate and valproic acid
• Capsules, sprinkle
• Capsules, extended-release
|• Tablets, delayed-release
• Tablets, extended-release
|• Migraine headaches prophylaxis|
|• Epilepsy - generalized tonic-clonic seizures, partial onset seizures or primary generalized tonic-clonic seizures
• Seizures associated with Lennox-Gastaut syndrome
|• Epilepsy - absence seizures (petit mal), complex partial seizures, simple partial seizures, generalized seizures
• Manic episodes of bipolar disorder
|• Bipolar disorder
• Binge-eating disorder
• Drug-induced weight gain
|• Maintenance treatment of bipolar disorder
• Bipolar depression
|Mechanism of action|
|• Topiramate produces multiple effects on receptors and ion channels.
• Topiramate blocks voltage-dependent sodium channels and potentiates the activity of GABA.
• Topiramate also suppresses excitatory glutamatergic transmission.
|• Divalproex sodium dissociates to the valproate ions in the gastrointestinal tract.
• Valproate increases the inhibitory effect of GABA.
• Also valproate blocks high frequency repetitive firing by slowing the rate of Na+ recovery.
|• 20 to 30 hours||• 9 to 16 hours|
|• 80-95%||• Divalproex is almost completely absorbed from the gastrointestinal tract.
• Divalproex extended-release tablets have decreased oral bioavailability.
|• Topiramate is not extensively metabolized.
• Topiramate is mainly eliminated unchanged in the urine.
|• Valproate is metabolized in the liver by beta and omega oxidation.
• Valproate metabolites are excreted in the urine.
|• No contraindications||• Hypersensitivity to divalproex sodium, valproic acid, sodium valproate
• Mitochondrial disorders
• Liver disease
• Urea cycle disorders
|• Weight loss
• Cognitive problems
• Word-finding difficulty
• Difficulty with memory, concentration
|• Weight gain
• Hair loss
• Abdominal pain
• Blurred vision
• Lack of muscle coordination
• Increased appetite
|• At high doses topiramate may interfere with oral contraceptives.||• Concomitant use of divalproex with drugs metabolized by CYP2C9 may result in significant drug interactions.|
|D||D / (X - for migraine prophylaxis )|
Topamax® vs Depakote® for Migraines
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%),
cognitive disturbances (20%)
|weight gain (24%),
hair loss (24%),
gastrointestinal symptoms (24%)
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||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|
Topamax® vs Depakote® for Seizures
Depakote (divalproex sodium) is indicated for:
- Complex partial seizures
- Simple and complex absence seizures.
Divalproex is effective against most types of seizures.
Topamax (topiramate) is indicated for:
- Partial-onset seizures
- New-onset generalized tonic-clonic ("grand mal")
- Seizures associated with Lennox-Gastaut syndrome
Topiramate is widely used for the treatment of epilepsy. It is effective against most seizure types, and is considered a broad-spectrum anticonvulsant. Topiramate seems to work better for patients who experience localization-related epilepsy than for those who experience generalized epilepsy.
Topiramate and valproate 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.|
- 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
- 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
- 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
Published: March 31, 2008
Last updated: February 01, 2018