Topiramate monotherapy

Groselj 1, Fuerrini R, Van Oene I, et al. Experience with topiramate monotherapy in elderly patients with recent-onset epilepsy. Acta Neurol Scand 2005 i i2 i44-i50. 

Ben-Menachem E et al Topiramate monotherapy in the treatment of newly or recently diagnosed epilepsy. Clin Ther 2008 30 1180. [PMID ... 

Daytime vigilance has been assessed in 14 newly diagnosed never medicated adults with focal epilepsy at baseline and 2 months after slow titration of topiramate to 200 mg/day (653). Multiple Sleep Latency Test (MSLT), visual simple and choice reaction time (VRT), and selfrating with the Epworth Sleepiness Scale were used for quantification of sleepiness, and compared with 14 healthy volunteers. At baseline MSLT scores were comparable. Two months after topiramate monotherapy, MSLT, VRT, and self-rating did not change significantly. 

The authors concluded that a short course of topiramate monotherapy dose not impair vigilance in this population. 

Bonanni E, Galli R, Maestri M, Pizzanelli C, Fabbrini M, Manca ML, Iudice A, Murri L. Daytime sleepiness in epilepsy patients receiving topiramate monotherapy. Epilepsia 2004 45(4) 333-7. 

A comparison of adverse drug reactions to topiramate in different diseases has been systematically reviewed pOl ]. All published randomized controlled trials that compared topiramate monotherapy with other drugs in epilepsy emd migraine were analysed. Four... 

In a retrospective study of non-ambulatory and neurologically impaired individuals in a long-term care facility, 13 of 24 who were taking topiramate monotherapy or polytherapy developed clinical evidence of urolithiasis after a mean treatment duration of 36 months [322 ]. 

The newer AEDs were first approved as adjunctive therapy for patients with refractory partial seizures. To date, lamotrigine, topiramate, and oxcarbazepine have received FDA approval for use in monotherapy in patients with partial seizures. Felbamate has monotherapy approval but causes significant side effects. 

Topiramate was also used as monotherapy in an open-label, collaborative, pilot study conducted by three groups of experienced investigators. Eleven acutely manic patients who were nonresponsive to lithium, VPA, or their combination continue to manifest significant symptoms with a mean baseline Young Mania Rating Scales (YMS) score of 32. Five of 11 patients had a substantial response (n = 3) or a partial response (n = 2) to the introduction of monotherapy with topiramate. 

For maintenance treatment, failure of first-line mood stabilizers or second-line atypical antipsychotics to control symptoms adequately may lead to monotherapy trials with other anticonvulsants such as carbamazepine, lamotrigine, gabapentin, and topiramate (third-line monotherapy). 

Waugh J, Goa KL. Topiramate as monotherapy in newly diagnosed epilepsy. CNS Drugs. 2003 17 985-992. 

Side effects. Many of the side effects reported to occur with topiramate have been found in patients receiving other antiepileptic drugs concurrently. Such side effects as ataxia, confusion, dizziness, fatigue, somnolence, memory disturbance, depression and agitation appear to be less frequent in those patients receiving topiramate as a monotherapy. Weight loss has been reported in many patients this effect may be due to drug induced anorexia. Topiramate has proven efficacious in the treatment of severe epilepsy. 

In a retrospective survey, behavioral changes occurred in nine of 69 children (median age 12 years) taking topiramate (634). Dosages in the affected children were 2.4— 8.5 mg/kg, and three children were taking monotherapy. Manifestations included school difficulties (635), mood swings (636), and aggression, irritability, and hallucinations (one case each). There was no apparent relation to dosage or titration rate. 

Sachdeo RC, Sachdeo SK, Levy RH, Streeter AJ, Bishop FE, Kunze KL, Mather GG, Roskos LK, Shen DD, Thummel KE, Trager WF, Curtin CR, Doose DR, Gisclon LG, Bialer M. Topiramate and pheny-toin pharmacokinetics during repetitive monotherapy and combination therapy to epileptic patients. Epilepsia 2002 43(7) 691-6. 

Dosing and Administration. Topiramate should be titrated slowly in order to avoid adverse events. Starting doses are 12.5 to 50 mg/day, increasing by 12.5 to 50 mg/day every week or every other week. The minimally effective dose of topiramate is approximately 200 mg/day. For patients on other AEDs, doses of greater than 600 mg/day do not appear to lead to improved efficacy and may cause increased adverse effects however, higher doses may prove beneficial to individual patients who tolerate them. Monotherapy doses as high as 1000 mg/day have been well tolerated and effective in some patients. 

The place in therapy of the newer anticonvulsants, such as gabapentin, levetiracetam, tiagabine, topiramate, and zon-isamide, is controversial. Many clinicians consider these agents to be less effective than established mood stabilizers based on initial studies and avoid them for monotherapy in bipolar disorder. 

A donble-blind stndy revealed topiramate to be eqniva-lent to valproate and carbamazepine in children and adnlts with newly diagnosed partial and primary generalized epilepsy. Additional stndies disclosed topiramate to be effective as monotherapy for refractory partial epilepsy and refractory generalized tonic-clonic seizures. Topiramate also was found to be sigifificantly more effective than placebo against both drop attacks and tonic-clonic seizures in patients with Lennox-Gastaut syndrome. 

Calabrese JR, Keck PE jr, McElroy SL et al. A pilot study of topiramate as monotherapy in the treatment of acute mania, j Clin Psychopharmacol 2001 21 340-342. 

Gilliam FG, Veloso F. Tolerability of topiramate as monotherapy in patients with recently diagnosed partial epilepsy. Epilepsia 1998 39(Suppl 6) 56. 

Absorption of topiramate is rapid and unaffected by food intake, with peak plasma concentrations being achieved approximately 2 hours after administration of a 400 mg dose. Metabolism of topiramate is not extensive and its oral plasma clearance is slow, with approximately 70% of an administered dose being eliminated unchanged by the kidneys. When used as monotherapy, topiramate has a... 

Topiramate is a sulfamate-substituted monosaccharide derived from fructose with a broad spectrum of AED activity. It is approved for monotherapy or as an adjunct drug for partial or primary generalized tonic-clonic seizures in patients older than 10 years, as adjunct therapy in children aged from 2 to 10 years with partial-onset seizures, and in persons older than 2 years with Lennox-Gastaut syndrome (40,53). Topiramate also is approved for the prophylaxis of migraine headaches. 

Sachdeo RC, Sachdeo SK, Walker SA, Kramer LD, Nayak RK, Doose DR. Steady-state pharmacokinetics of topiramate and carbamazepine in patients with epilepsy during monotherapy and concomitant dierapy. Epilepsia (1996) 37, 774-80. 

Observational studies In a prospective, long-term observational study of topiramate as initial monotherapy in 229 Chinese patients with newly diagnosed epilepsy the retention rate was 76% at 1 year and 47% at 6 years [278 ]. Causes that led to treatment failure were lack of efficacy (7.4%), adverse reactions (11%), and loss to follow-up (16%). Adverse reactions occurred in 129 patients (56%). The most common included memory impairment (13%), weight loss (8.7%), nausea (7.3%), speech difficulty (5.7%), and somnolence (4.8%). Seven patients (3.1%) developed renal calculi. Most of the adverse reactions occurred in the first 6 months of treatment, especially during the titration period. 

Hu Y, Lu Y, Yu W, Shen D, Xiao Z, Xi Z, Wang X. Long-term retention rate of topiramate as initial monotherapy in Chinese patients with newly diagnosed epilepsy a prospective, observational study. Epilepsy Res 2010 90(3) 278-84. 

All the available evidence for the use of topiramate as monotherapy in patients with newly or recently diagnosed epilepsy has been examined in a systematic review of three randomized, double-bUnd, controlled trials which recruited more than 1000 patients [302 ]. The most common adverse events associated with topiramate 50-500 mg/day generally occurred early in the course of treatment and were nervous system-related effects headache (15-25%), dizziness (12-19%), fatigue (11-23%), somnolence (10-17%), anorexia (8-10%), insomnia (7—10%), and hyperesthesia (5— 10%). Adverse events that were likely to have been related to the carbonic-anhy-drase activity of topiramate (e.g. paresthesia, changes in serum bicarbonate) were frequent (13-35%) but were not usually considered clinically relevant Renal calculi occurred infrequently (1%). The most frequent adverse events during maintenance therapy were headache (20%), reduced appetite (11%), and weight loss (11%). 

Sankar R, Ramsay E, McKay A, Hulihan J, Wiegand F. CAPSS-311 Study Group A multicenter, outpatient, open-label study to evaluate the dosing, effectiveness, and safety of topiramate as monotherapy in the treatment of epilepsy in clinical practice. Epilepsy Behav 2009 15(4) 506-12. 

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