Somnolence topiramate

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. 

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. 

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. 

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. 

The response to topiramate has been evaluated in 97 patients with Lennox-Gastaut syndrome in a long-term, open-label extension to a double-blind, placebo-controlled trial (19). The most common adverse events, apart from childhood illnesses, were somnolence and anorexia. 

Fulminant liver failure developed in a 39-year-old woman after she had taken topiramate for about 4 months, in addition to carbamazepine. The condition occurred after she increased the dosage of topiramate to 300 mg/day, and was preceded for a few days by tiredness and somnolence (50). She made an uncomplicated recovery after hver transplantation. Histological examination showed centrilobular necrosis, compatible with drug-induced fulminant liver failure. 

Topiramate is well tolerated. The most common adverse effects are somnolence, fatigne, weight loss, and nervousness. It can precipitate renal calculi, which is most likely due to inhibition of carbonic anhydrase. Topiramate has been associated with cognitive impairment and patients may complain abont a change in the taste of carbonated beverages. 

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. ... 

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. 

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 overdose Seven cases of acute topiramate toxicity observed in two clinical units of poison centers have been described [333" ]. The doses of topiramate were 11-218 mg/kg. Somnolence was characteristic and vertigo, agitation, and mydriasis were less common. There was a metabolic acidosis in four cases. One patient who had not previously taken topiramate and who had taken 31 mg/kg had three secondarily generalized tonic-clonic seizures. All recovered without sequelae and were discharged after 4-8 days. 

In 12 patients (3-35 years) diagnosed with Dravet syndrome who received fenfluramine as an add-on therapy, a slight thickening of one or two heart valves was detected in two patients. Loss of appetite was reported in two patients, who were both on combination therapy with topiramate, a drug also known to reduce appetite. Additionally, fatigue was reported in two patients, and excessive somnolence in one patient [56 ]. 

Observational studies In a study of topiramate for intractable childhood generalized epilepsy with epileptic spasms, adverse effects were observed in 13 of 33 patients and included somnolence, anorexia, and irritability. Seizure aggravation was observed in six patients [16(P]. 

The long-term effects of topiramate on adaptive behavior in infants with epilepsy were assessed [161 ]. A clinically significant decline in scores on the Vineland Scales of Adaptive Behavior occurred in infants treated with topiramate. Of note, however, Vineland scores were below average at pretreatment baseline in these patients. Anorexia was noted in 35% of patients and somnolence in 27%. 

Drug-drug interactions In a placebo-controlled study evaluating the combination of topiramate and nortriptyline for headache prophylaxis, 44 patients were given topiramate 100 mg/day and nortriptyline 30 mg/day, while 17 took topiramate 100 mg/day plus placebo [174 ]. Side effects reported by those taking both medications, as opposed to topiramate alone, included dry mouth (18%), somnolence (9%), hair loss (2.3%), heartburn (2.3%), dry mouth (4.5%), and memory disturbance (6.8%). 

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