What is the use of Topamax (Topiramate)?

From the Guidelines

Topamax (topiramate) should be used with caution and as part of a combination therapy, such as phentermine-topiramate ER, for weight loss in adults with obesity, with a recommended target dose of 15 mg/92 mg daily, as it has shown moderate to large magnitude of weight loss, while considering the potential risks and benefits, as noted in the 2022 AGA clinical practice guideline on pharmacological interventions for adults with obesity 1.

Key Considerations

• The combination of phentermine and topiramate has been shown to be effective for weight loss, with a recommended starting dose of 3.75 mg/23 mg and a target dose of 15 mg/92 mg daily 1.
• Topiramate has been used off-label for weight loss, but its exact mechanism of action is unknown, and it may reduce energy consumption through modulation of gamma-aminobutyric acid receptors in the central nervous system 1.
• Common side effects of topiramate include tingling sensations, fatigue, dizziness, decreased appetite, weight loss, and cognitive effects, and patients should drink plenty of water to reduce the risk of kidney stones 1.
• The medication should be taken consistently and not stopped suddenly without medical supervision, and patients should inform their doctor about all other medications they're taking, as topiramate can interact with birth control pills, reducing their effectiveness 1.

Special Clinical Considerations

• Phentermine-topiramate ER should be avoided in patients with a history of cardiovascular disease or uncontrolled hypertension, and caution is advised in patients with significant nephrolithiasis or untreated hyperthyroidism 1.
• Female patients with child-bearing potential should be counseled on the risks of teratogenicity and consistent use of reliable contraception while using phentermine-topiramate ER, and monitoring with monthly pregnancy tests can be considered 1.
• The medication is classified as a schedule IV-controlled substance based on concerns for abuse and dependence, and patients should be aware of the potential risks and benefits of treatment 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Topamax Overview

• Topamax, also known as topiramate, is a medication used to treat epilepsy and prevent migraines 2, 3, 4, 5, 6.
• It has been registered since July 1998 and has market authorization for the treatment of patients with intractable partial and secondarily generalized seizures 2.

Mechanism of Action

• The anticonvulsant effect of topiramate is based on three mechanisms:
  • Modulating the blocking of the Na channels activated by voltage, depending on status
  • Potentiation of GABAA-mediated inhibiting neurotransmission
  • Inhibition of excitatory neurotransmission by blocking APMA glutamate receptors 2

Efficacy in Epilepsy

• Topiramate exhibits a substantial anticonvulsive effect on partial seizures both with and without secondary generalization 2.
• The median reduction in seizure frequency using topiramate as adjunct therapy was 44% 2.
• In 44% of patients, seizure frequency was reduced by more than 50%, and seizure reduction was more than 75% in nearly half of these (i.e., in 21% of all patients), while 5% of patients remained completely free of seizures 2.

Efficacy in Migraine Prevention

• Topiramate is effective for the preventive treatment of migraine, reducing migraine frequency and acute medication use, improving quality of life, and reducing disability in patients with episodic migraine and in those with chronic migraine with or without medication overuse headache 3, 4, 5, 6.
• Topiramate achieved a greater reduction in migraine attack severity and HIT-6 score compared to valproate in a randomized controlled multi-center trial 5.

Side Effects

• Adverse events most often caused central nervous disturbances, weight loss, the development of renal calculi, and impairment of cognitive functions 2.
• Paresthesia is a common occurrence early in treatment but is rarely cause for terminating topiramate treatment 3.
• Cognitive problems occur much less frequently than paresthesia but are more troublesome in terms of treatment discontinuation 3.
• Topiramate has metabolic effects that favor the development of metabolic acidosis and possibly renal stones 3.
• First-trimester exposure to topiramate monotherapy is associated with increased occurrence of cleft lip with or without cleft palate (Pregnancy Category D) 3.

Dosage and Administration

• It is recommended to start therapy with topiramate at a daily dosage of 25 mg, increasing by 25 mg every week up to 200-400 mg/day but not exceeding 1000 mg/day 2.
• Extended-release (XR) formulations of topiramate, such as Qudexy XR and Trokendi XR, were specifically designed to achieve the adherence benefits of q.d. dosing but with more favorable steady-state plasma concentrations over the 24-hour dosing interval vs IR topiramate b.i.d. 3.