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.
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| Topiramate | Divalproex sodium |
| Brand names | |
| • Topamax® • Trokendi® XR • Qudexy® XR |
• Depakote® • Depakote® ER • Depakote® Sprinkle |
| Drug class | |
| • Anticonvulsants | |
| • Sulfamate-substituted monosaccharide | • Mood stabilizer • Compound comprised of sodium valproate and valproic acid |
| Dose formulations | |
| • Tablets • Capsules, sprinkle • Capsules, extended-release |
• Tablets, delayed-release • Tablets, extended-release • Capsules |
| FDA-approved indications | |
| • 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 |
| "Off-label" uses | |
| • Bipolar disorder • Binge-eating disorder • Obesity • Drug-induced weight gain |
• Maintenance treatment of bipolar disorder • Bipolar depression • Psychosis • Schizophrenia |
| 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. |
| Half-life | |
| • 20 to 30 hours | • 9 to 16 hours |
| Oral bioavailability | |
| • 80-95% | • Divalproex is almost completely absorbed from the gastrointestinal tract. • Divalproex extended-release tablets have decreased oral bioavailability. |
| Metabolism, Elimination | |
| • 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. |
| Contraindications | |
| • No contraindications | • Hypersensitivity to divalproex sodium, valproic acid, sodium valproate • Mitochondrial disorders • Liver disease • Urea cycle disorders |
| Side effects | |
| • Weight loss • Paresthesia • Cognitive problems • Word-finding difficulty • Anorexia • Fatigue • Dizziness • Difficulty with memory, concentration |
• Weight gain • Hair loss • Abdominal pain • Constipation • Dyspepsia • Blurred vision • Lack of muscle coordination • Weakness • Increased appetite • Dizziness |
| Drug interactions | |
| • At high doses topiramate may interfere with oral contraceptives. | • Concomitant use of divalproex with drugs metabolized by CYP2C9 may result in significant drug interactions. |
| Pregnancy category | |
| D | D / (X - for migraine prophylaxis ) |
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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 | 58% 40 patients of 69 |
51% 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%) |
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 |
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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 (64%) |
9 patients of 16 (56%) |
| 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. | ||
Further reading
References
- 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
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