Paresthesia topiramate

Topiramate is recently approved by the FDA for migraine prophylaxis. Dose is initiated at 25 mg/day and increased slowly to minimize side effects, which may include paresthesias, fatigue, anorexia, diarrhea, weight loss, difficulty with memory, and nausea. Kidney stones, acute myopia, acute angle-closure glaucoma, and oligohidrosis have been infrequently reported. 

Paresthesia Paresthesia, an effect associated with the use of other carbonic anhydrase inhibitors, appears to be a common effect of topiramate. 

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. 

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). 

In an open study of the effects of topiramate 100-1600 mg/day in 292 adults (mean age 33 years) with partial and/or generalized seizures previously resistant to antiepileptic drug therapy over 50% of the patients achieved at least a 50% reduction in seizures (1). The most commonly reported adverse events were related to the central nervous system, including headache, difficulty in concentrating, somnolence, anorexia, fatigue, dizziness, nervousness, nausea, confusion, and paresthesia 32% discontinued because of adverse events. 

Topiramate had a beneficial effect on benign essential tremor in an open study in nine patients (2). Six patients complained of fatigue and two discontinued therapy four complained of paresthesia. 

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 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. 

The most common side-effects of topiramate are paresthesia (27%), headache (21%), fatigue (20%), dizziness (14%), somnolence (1 3%), anorexia (11%), and weight loss (11 %). Less common side-effects, but with important clinical implications, are depression (7%), difficulty with concentration (7%), and confusion (5%). " As with other anhydrase inhibitors, topiramate has been associated with kidney-stone formation, and the incidence of nephrolithiasis is estimated to be 2-4 times higher than that expected in a similar untreated population. Many of the central nervous system effects of topiramate, including cognitive complaints, can be managed by gradual introduction and dose escalation. ... 

The anticonvulsant topiramate has also been reported to be effective in reducing binge and purge frequencies in comparison with placebo. However, bothersome side-effects such as paresthesias, impaired cognition, and renal calculi may lessen its usefulness. Naltrexone is a possible adjunct in patients who are refractory to SSRIs, especially those with comorbid alcoholism and/or self-injurious behavior. ... 

Clozapine In a 12-week open study of the potential benefits of topiramate in 16 clozapine-treated individuals with schizophrenia, including 5 individuab with type 2 diabetes, there was a 14% improvement in total BPRS scores and a statistically significant 2.5% reduction in body weight paresthesia was the most common adverse reaction [39 ]. 

In 40 selected patients, age range 18-64 years, who were randomized in an open study for migraine prophylaxis to topiramate 25, 50, 75 or 100 mg as an evening dose paresthesia was by far the most common adverse reaction (55% of patients) and the incidence was dose related [280. Fatigue, giddiness, diarrhea, nausea, and drowsiness were reported in a few patients, but there was no apparent dose-effect relation. 

In a small, open study of topiramate for the prevention of cluster headache in 12 Asians, the initial dose was 50 mg bd, increasing by 50-100 mg/day every 3-7 days to a maximum of 400 mg/day. Adverse reactions included paresthesia (84%), slow speech (54%), and dizziness (46%). Two patients withdrew because of adverse events. 

In an open study of topiramate 50 or 100 mg/day in 30 patients with migrainous vertigo, 19 had paresthesia, 11 fatigue, 8 memory and concentration problems, 14 reduced appetite, and 4 weight loss [281 ]. Four withdrew at the end of the first month because of adverse reactions. 

In 20 subjects in a 12-week, open study in clozapine-treated individuals with schizophrenia the initial dose of topiramate was 25 mg bd and the dose was titrated weekly, as tolerated, up to a maximum of 200 mg/ day [282 ]. There was paresthesia, the most common adverse reaction, in 10 patients and it resolved or abated with topiramate dosage reduction. Other adverse reaction scales showed no significant changes. 

Nervous system In a review of several clinical studies of the use of topiramate in different indications (alcohol dependence, essential tremor, binge-eating disorder, bulimia nervosa, migraine, and epilepsy), the percentages of drug-induced nervous system adverse reactions, in particular paresthesia, differed greatly between the different disorders dropouts due to adverse events varied from 2% in those with bulimia nervosa to 29% in those with migraine [289 ]. 

Observational studies Topiramate has been retrospectively evaluated in 227 patients with symptomatic epilepsy, of whom 12 withdrew because of adverse effects [292 ]. The incidence of adverse effects was 36% and the most common were weight loss, memory impairment, paresthesia, headache, and dizziness, most were mild to moderate in intensity and transient. 

In a single-center, 8-week titration and 4-week maintenance period, double-blind, randomized study of topiramate or amitriptyline, alone or in combination, in 73 patients with migraine with or without aura all the treatments resulted in significant improvements in all efficacy measures [296 ]. Discontinuation rates due to adverse events were 8.3%, 14%, and 4.3% with topiramate, amitriptyline, and the combination respectively. The most common adverse effects in the topiramate group were paresthesia (35% at 8 weeks and 40% at 12 weeks), weight loss (25% and 35% respectively), and memory impairment (10% and 15%, respectively). 

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%). 

Drug formulations In an assessment of the safety of intravenous topiramate at a dose of 25 mg, seven of 90 patients reported adverse effects. These included nausea and vomiting, perioral paresthesias, and paresthesias of the extremities [173 -]. 

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