Adverse effects topiramate

Ben-Zeev B, Watemberg N, Augarten A, Brand N, Yahav Y, Efrati O, Topper L, Blatt I. Oligohydrosis and hyperthermia pilot study of a novel topiramate adverse effect. J Child Neurol 2003 18(4) 254-7. 

Topiramate Topamax Suspension 300 mg/5 mL Tablet 25, 100, 200 mg Doses should be slowly adjusted up and down according to response and adverse effects (e.g., 150-300 mg twice daily and increase by 300-600 mg/day at weekly intervals) 50-200 mg/day in divided doses drug-drug interactions than carbamazepine, but causes more gastrointestinal side effects and hyponatremia Evidence is limited regarding efficacy Not recommended for the... 

At least three drugs are effective against absence seizures. Two are nonsedating and therefore preferred ethosuximide and valproate. Clonazepam is also highly effective but has disadvantages of dose-related adverse effects and development of tolerance. Lamotrigine and topiramate may also be useful. 

Changes in body weight associated with anticonvulsants have been reviewed (116), including the effects of the antiepileptic drugs that have been most commonly associated with this adverse effect (valproic acid, carbamazepine, vigabatrin, and gabapentin) (117). Unlike most anticonvulsants, topiramate, felbamate, and zonisamide can cause weight loss. 

In a 10-week randomized, double-blind, study in 64 women with recurrent major depressive disorder, the dosage of topiramate was titrated up to 200 mg/day (1130). There were no serious adverse effects, including psychotic symptoms and suicidal acts. Adverse effects such as headache, fatigue, dizziness, and paresthesia were rated as mild. After 10 weeks there was weight loss, which was usually regarded as beneficial. 

Adverse effects These are primarily related to CNS and Gl disturbances. They include impaired concentration, dizziness, ataxia, diplopia, somnolence, nervousness, and confusion, as well as nausea and weight loss. Renal stones have been reported in 1.5 percent of patients. Topiramate is teratogenic in animals, and should be avoided during pregnancy. Inducers of drug metabolism such as phenytoin and carbamazepine decrease topiramate serum concentrations by approximately 50 percent. Topiramate decreases ethinyl estradiol concentrations of oral contraceptive preparations, and individuals should supplement the amount of ethinyl estradiol. 

A 26-year-old woman with bipolar I disorder took lithium and valproate, and sometimes additional risperidone and lamotrigine. Both risperidone and lamo-trigine produced dermatological adverse effects. Her serum lithium concentration was 0.82 mmol/1. Topiramate 75 mg/day was added. A week later, she continued to show a mixed state with mostly manic features and a raised lithium concentration of 1.24 mmol/1. The lithium concentration continued to increase over the next 4 days to 1.97 mmol/1 even though the lithium dosage was reduced from 900 to 750 mg/day. Lithium was withdrawn and the lithium concentration fell. Lithium was then restarted at half the admission dose to achieve a blood concentration of 0.67 mmol/1. Subsequent increases in the dose of topiramate resulted in further increases in the lithium concentration. 

Risperidone has also been used in combination with topiramate in a Spanish multicenter study in 58 patients (28 men and 30 women mean age 41 years) with bipolar I disorder, with manic but not mixed episodes (20). Risperidone (mean dose 2.7 mg/day) and topiramate (mean dose 236 mg/day) were started with a maximum 48-hour time difference risperidone was used for acute manic symptoms and topiramate for longer-term stabilization and prevention of relapse. The incidence of any adverse event was 64%, mostly somnolence, paresthesia, dizziness, tremor, weight loss (n = 27 mean change -1.1 kg), extrapyramidal disorders, gastrointestinal effects, and cognitive disturbances. One patient developed tardive dyskinesia during the study and there were five dropouts because of adverse effects adverse effects that required withdrawal of risperidone but not topiramate were amenorrhea (n = 3) and sexual dysfunction (n = 1). 

The cognitive adverse effects of topiramate have been studied in 62 patients taking carbamazepine who had addon therapy with either topiramate, valproic acid, or... 

Topiramate is used in the adjunctive therapy of partial seizures and some types of generalized seizure. Most of its adverse effects relate to the central nervous system. 

In a 3-year retrospective review of the use of topiramate in 51 children aged 3-16 years with partial and generalized epilepsy, 15 children had a greater than 50% reduction in their seizure frequency and four became seizure free (4). Adverse effects were reported in 29 patients most were related to behavioral and cognitive difficulties less common effects included anorexia, weight loss, and headache. Topiramate was withdrawn in 25 patients in 20 cases because of adverse effects. 

In 18 patients with severe myoclonic epilepsy in infancy topiramate caused reduced seizure frequency in most (5). There were adverse effects in nine patients, eight with a weekly titration schedule and one with a fortnightly schedule. They were usually minor and transient nervous... 

Among the adverse effects of topiramate are reduced appetite and weight loss, and this has been put to use in the treatment of binge eating in an open study in 13 patients (6). Nine patients had a moderate or better response, two had moderate or marked responses that subsequently diminished, and two had a mild response or none. Neurological adverse effects were the most common. Three patients discontinued topiramate because of adverse effects, and two resumed at a later date without significant recurrence. 

The efficacy and tolerability of topiramate have been studied in 170 patients with refractory epilepsy (7). The most common adverse effects resulting in withdrawal were fatigue, weight loss, irritability, paresthesia, depression, and headache. Three patients developed renal calculi but continued therapy. 

The effect of topiramate for 6-18 months in 34 children with drug-resistant epilepsy has been studied (8). Adverse effects were reported in nine patients, appetite suppression in five, behavioral disturbances in three, somnolence in two, and poor concentration in one. 

The results of six double-blind, placebo-controlled trials with topiramate in adults with treatment-resistant partial-onset seizures with or without secondary generalization have been analysed (14). Seizures were reduced by at least 50% in 43% of topiramate-treated patients and in 12% of placebo-treated patients. The most common treatment-related adverse events were dizziness, somnolence, fatigue, psychomotor slowing, nervousness, paresthesia, ataxia, memory difficulty, and speech problems. These effects were generally mild to moderate, usually occurred early in treatment, often during titration, and resolved with continued treatment. Other adverse effects were weight loss and, in a few patients, renal calculi. 

In the comparison of four anticonvulsants mentioned above, the commonest adverse effect of topiramate in 28 patients was irritability, which occurred in seven of ten patients who discontinued therapy because of adverse effects (18). 

The concentrations of topiramate have been measured in plasma and breast milk in five women with epilepsy during pregnancy and lactation (52). The umbilical cord plasma/maternal plasma ratios were close to unity, suggesting extensive transplacental transfer of topiramate. The mean milk/maternal plasma concentration ratio was 0.86 (range 0.67-1.1) at 2-3 weeks after delivery. The milk/maternal plasma concentration ratios at sampling 1 and 3 months after delivery were similar. Two of the breast-fed infants had detectable (>0.9 pmol/l) concentrations of topiramate 2-3 weeks after delivery, although they were below the limit of quantification (2.8 pmol/l), and one had an undetectable concentration. Thus, breastfed infants had very low topiramate concentrations. No adverse effects were observed in the infants. 

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