Managing the side effects of Topiramate (Topamax)

Topiramate is an anti-convulsant medication that has been approved for use in Australia for the treatment of epilepsy in adults and children.1 Topiramate has also been approved for the treatment of migraine headaches in adults when alternative treatments (beta-blockers and pizotifen) are contraindicated or not well tolerated.1 Reports of common and potentially unpleasant side effects of topiramate have caused some concern amongst patients. However, these side effects tend to be transient, controllable and/or avoidable if the dosage of topiramate is properly managed.

Several side effects have been reported following the use of topiramate as add-on therapy for epilepsy. In particular, more than 10% of adult patients administered topiramate reported paraesthesia, dizziness, fatigue, anorexia, weight decrease, speech problems, diarrhoea, cognitive difficulties (such as poor concentration and memory), and ataxia.^2,3 Side effects experienced by 1-10% of patients included altered sense of taste, hypoaesthesia, insomnia, nausea, renal calculi  and mood problems (including aggression, depression and psychosis). Similar side effects have been reported following the use of topiramate to treat migraine. However the amount of topiramate required to reduce migraine occurrence is lower, therefore the occurrence of side effects also tends to be lower.³ Very common side effects (>10%) in children include personality disorder, anorexia, nervousness, somnolence and fatigue.³

Side effects associated with the functioning of the central nervous system (CNS), including dizziness, slowed thinking, somnolence, ataxia, fatigue, confusion, and impaired concentration, tend to be temporary, but can be avoided.⁴ In general, CNS side effects can be avoided in adults by administering topiramate at a low starting dosage (approx. 25mg), and escalating the dose slowly, (approx. 25mg per week).⁴ Side effects are also experienced more often at higher target doses of topiramate. Therefore a target adult dose of 100mg for epilepsy monotherapy or for the treatment of migraine is recommended (recommended doses are higher for epilepsy add-on therapy).^3,4 Patients should be reassured prior to treatment that CNS side effects may be experienced. It should be emphasised that these side effects are likely to be temporary. Early research trials investigating the efficacy of topiramate in the treatment of epilepsy found that side effects such as fatigue and cognitive impairment resolved within 2 months in almost 90% of cases.⁴

Paraesthesia is the most commonly reported side effect of topiramate. In trials assessing the efficacy of topiramate for migraine prevention between 35% and 50% of patients in the treatment groups reported paraesthesia (compared with 6% amongst controls). Paraesthesia was mild and usually transient and did not result in nerve damage.⁴ Alerting patients to the possibility that they may experience temporary numbness and tingling around the mouth and in the limbs, may reduce anxiety if paraesthesia occurs.⁵ Current research is examining the possibility that treatment with potassium supplementation may reduce the severity of paresthesia.^4,5

Other side effects such as renal calculi, an altered sense of taste (taste perversion) and weight loss can also be managed. Renal calculi or kidney stones can be avoided by increasing fluid (preferably water) intake.^3-5 Taste perversion is usually limited to carbonated (fizzy) drinks due to the chemical makeup of topiramate. Patients should be advised that carbonated drinks (and potentially other drinks or foods) may taste odd or unpleasant. This side effect is completely harmless but prior warning can assist in reducing patient anxiety.⁵ Weight loss with topiramate is usually in the range of 2-4% of total body weight.^3,4  Adults and children of normal or low body weight should be advised to eat higher calorie meals, avoid fasting and/or consider taking additional nutritional supplements.^4,5

Cognitive impairments associated with topiramate are usually dose related. Therefore lower doses will result in fewer problems with memory, language and concentration.⁵ Simple strategies can be adopted to help tolerate these problems if they occur, for example writing things down, and keeping lists. An inability or delay in ‘finding the right word’ is often reported.⁵ If patients experience these symptoms, it is worth discussing with patients whether the cognitive impairments are tolerable in light of improvements in epileptic or migraine symptoms.

Further research has suggested that mood disturbances such as aggression, psychosis, anxiety and depression are related to higher starting doses, rapid dose titration, a previous history of psychiatric illness or a family history of psychiatric illness.⁶ When titration reaches 100mg per week, rates of psychiatric problems have been reported in 12% of patients.⁶ Therefore dose titrations closer to 25 mg per week are recommended. In the event of psychiatric side-effects, a dose reduction and therapy discontinuation may be necessary.⁶ Patients with a personal or family history of psychiatric illness should be carefully assessed for their suitability for topiramate therapy, and then carefully monitored during therapy.

In general, side effects can be avoided by starting topiramate at a low dose and increasing it slowly to the lowest possible target dosage. Alternative or additional strategies can be adopted to alleviate side effects if they occur. Distress or anxieties about side effects of topiramate are best addressed by reassuring patients prior to treatment. If side effects of topiramate cannot be managed, or are particularly distressing for a patient, interfere significantly with their daily functioning, or outweigh the intended therapeutic benefits, then discontinuation and alternative treatments should be considered.

Reference:

1. Department of Health and Ageing. Topiramate in the current Pharmaceutical Benefits Schedule [document on the Internet]. Australia: Commonwealth Government of Australia [updated 2008 June 25; cited 2008 July 30]. Available from: http://www.pbs.gov.au/html/healthpro/search/results?term=topamax&scope=PBS+STATIC&form-type=simple
2. National Prescribing Service RADAR (Rational Assessment of Drugs and Research). Topiramate (Topamax) for migraine prevention [document on the internet]. Surry Hills: National Prescribing Service Limited; c2005 [Updated November 2007; Accessed July 30 2008]. Available from: http://www.npsradar.org.au/site.php?page=1&content=/npsradar/content/topiramate.html
3. Topamax Tablets and Sprinkle Capsules Product Information. North Ryde Australia: JANSSEN-CILAG Pty Ltd. 2008 May 5
4. Silberstein SD. Topiramate in Migraine Prevention. Headache 2005; 45[Suppl 1]: S57-S65.
5. Brandes JL. Practical Use of Topiramate for Migraine Prevention. Headache 2005; 45[Suppl 1]: S66-S73.
6. Mula M, Trimble M R, Lhatoo SD, Sander JWAS. Topiramate and Psychiatric Adverse Events in Patients with Epilepsy. Epilepsia, 2003; 44(5): 659-663.