Weight loss topiramate

Dursun SM, Devarajan S. Clozapine weight gain, plus topiramate weight loss. Can J Psychiatry 2000 45(2) 198. 

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. 

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. 

Topiramate, felbamate, and zonisamide are associated with weight loss. In animals topiramate reduced food intake, but also reduced energy disposition in the absence of reduced intake. In addition, topiramate increased lipoprotein lipase activity in adipose tissue, possibly reflecting enhanced regulatory thermogenesis. In humans and animals topiramate reduces leptin concentrations. With felbamate weight loss is almost always associated with... 

Weight loss with topiramate can occasionally be extensive (1127). 

In this case the weight loss was a beneficial collateral effect of topiramate. 

In a retrospective chart review, weight loss was assessed in 214 patients with psychiatric disorders taking topiramate (1128). Patients taking either lithium or valproate gained a mean (SD) of 6.3 (9.0) kg and 6.4 (9.0) kg respectively, whereas patients taking topiramate lost 1.2 (6.3) kg. Similar statistically significant results were found in the bone mass index. 

In an 8-week, double-blind, placebo-controlled study of topiramate 250 mg/day in the treatment of aggression in 42 men with borderline personality disorder there was significant weight loss of 5.0 kg (95% Cl = 3.4, 6.5) (1129). There were no psychotic symptoms or other... 

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. 

Topiramate can be described as a broad-spectrum neurotherapeutic agent with multiple modes of action, and its weight-loss promoting activity came to attention in trials of therapy for epilepsy [104], and explored further in animal experiments [105, 106], It has also been successfully used in the treatment of obesity associated with eating disorders [107, 108], As specific weight-loss therapy in one short-term [109] and one long-term study [110] in non-diabetics without co-morbid neuropsychiatric conditions, topiramate has been shown to produce a modest dose-related benefit compared to placebo, and with a reasonable side-effect profile. 

Bray GA, Hollander P, Klein S, Kushner R, Levy B, Fitchet M, Perry BH (2003) A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res 11 722-733... 

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). 

Some patients with psychotropic drug-induced weight gain may experience significant weight loss (>7% of body weight) with topiramate up to 200 mg/day for 3 months, but this is not typical, is not often sustained, and has not been systemically studied... 

Topiramate is used as adjunctive treatment for partial seizures, with or without secondary generalisation. It use is limited by its unwanted effects, particularly sedation, naming difficulty and weight loss. Acute myopia and raised intraocular pressure may occur. 

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. 

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 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 efficacy and safety of topiramate has been studied in 46 adult Chinese patients with refractory partial epilepsy in a randomized, double-blind, placebo-con-trolled study (15). Adverse events were mostly mild and transient, with no significant differences between treatment groups. Two patients taking topiramate had weight loss. 

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