TOPIRAMATO 4.1.1 THERAPEUTIC
1. A reduction in seizure frequency and severity is indicative of therapeutic response totopiramate. E. BULIMIA NERVOSA
- Topiramate was associated with a greater reduction
in the mean weekly number of binge and/or purge days
- Topiramate may have an effect on some behavioral
- Topiramate improved binging and purging behavior
in 3 out of 5 patients in a case series
- Topiramate resolved bulimia nervosa in a patient
a. The percentage reduction in the mean weekly number of binge and/or purge days wasgreater in the topiramate arm compared to placebo in a randomized, double-blinded trial. Patients (n=64) with DSM-IV bulimia nervosa were randomized to receive eithertopiramate or placebo for 10 weeks. Topiramate was initiated at 25 milligrams/day(mg/d) for 1 week and then was titrated by 25 to 50 mg per week to 400 mg/d or to themaximally tolerated dose (median dose 100 mg/d). Patients recorded the incidence ofbinge and purge episodes as well as time and quantity of medication taken in a dailydiary. Intent-to-treat analysis demonstrated a 44.8% reduction in the mean weeklynumber of binge and/or purge days in the topiramate arm compared to a 10.7% reductionin the placebo arm (p=0.004). Topiramate was associated with a 48.2% reduction inmean weekly number of binge days and a 49.2% reduction in mean weekly bingefrequency compared to 17.7% (p=0.015) and 28% (p=0.071) with placebo. Topiramatealso decreased mean weekly purge days 43.4% and mean weekly purge frequency 49.8%
compared to 16.6% (p=0.016) and 21.6% (p=0.016) with placebo. A secondary analysisexamined the effect of topiramate on psychiatric measures. Eating Disorder Inventory(EDI) and Eating Attitudes Test (EAT) were used to examine pathologic eating attitudesand behaviors. Changes in EDI subscale scores for bulimia/uncontrollable overeating,body dissatisfaction and drive for thinness were significantly different from placebo(p=0.005, 0.007 and 0.002, respectively). However changes in ineffectiveness,perfectionism, interpersonal distrust, interoceptive awareness and maturity fears werenot. EAT subscale scores for bulimia/food preoccupation and dieting also weresignificantly different from placebo (p=0.019 and 0.031), however oral control was not. Fatigue, flu-like symptoms, and paresthesias were the most common adverse effectsassociated with topiramate use. Comparison studies with psychotherapy and/orantidepressants are needed to elucidate what role, if any, topiramate has in the treatmentof bulimia nervosa (Hoopes et al, 2003; Hedges et al, 2003).
b. In a case series, topiramate improved binging and purging behavior in 3 out of 5patients. Each patient had comorbid psychiatric disorders and history of bulimia rangingfrom 8 to 30 years. Topiramate doses ranged from 25 to 400 milligrams (mg) daily, themost common dose being 200 mg daily. In three patients, binging and purging stoppedcompletely within 4 weeks and remained abated for 5 months, 7 months and greater than18 months. In 1 unsuccessful trial, a patient gradually achieved a 2-month, symptom-freeperiod. However after 12 months of treatment his purging had returned to baseline levels. Of note, his topiramate dose was limited to 90 mg daily due to paresthesias in his handsand feet. The fifth patient was prescribed topiramate 25 mg daily, however on day 6treatment was discontinued due to severe abdominal pain, intestinal gas, constipation andrectal bleeding (Barbee, 2003).
c. Use of TOPIRAMATE by a 34-year-old woman with bulimia nervosa and partialcomplex epilepsy led to complete resolution of her eating disorder (Knable, 2001). Thepatient had a history of depression, compulsive overeating, and excessive weight gaindating back to 8 years of age. While she was in graduate-level professional school, shebegan the practice of inducing vomiting with her fingers or syrup of ipecac, with purginginduced several times a week. This pattern continued for a decade, and was not improvedby treatment with fluoxetine, sertraline, or venlafaxine. At age 29, the patientexperienced 2 losses of consciousness preceded by altered visual perception and intensethirst. The second loss of consciousness was accompanied by tonic posturing of all theextremities; she began treatment with phenytoin. During 5 years of phenytoin therapy,she continued to binge and purge, had recurrent bouts of depression, and exhibited anepisode of self-mutilation with broken glass. Her auras became more frequent and sheexperienced a partial complex seizure with clonic movements of her right arm and leg(despite a phenytoin concentration of 23.4 micrograms/milliliter). Topiramate wasinitiated and titrated to 150 milligrams/day. Her aura and convulsions ceased; herappetite was reduced, she lost 10 pounds, and her bulimia resolved. At 15 months offollow-up, she remained bulimia-free.
C. BINGE-EATING DISORDER
- Reduction of binge-eating episodes in 1 case
a. Binge-eating disorder resolved in a 22-year-old woman with morbid obesity (bodymass index 42.5 kilograms/square meter) after therapy with TOPIRAMATE. Over thepast 4 years, she had exhibited binge-eating episodes over 3 to 4 days per week. Herbehavior met the proposed DSM-IV criteria for binge-eating disorder without psychiatricor neuro-endocrine comorbidity. The patient had received nutritional counseling forweight loss. She failed to lose weight and continued binge-eating episodes duringtreatment with amphetamine-like anorectic agents, a course of fluoxetine 60 milligrams(mg)/day, and a short trial with sibutramine 15 mg/day, which she could not tolerate. Topiramate was initiated at 25 mg twice daily. After 2 weeks, her dose was increased by25 mg/week until she reached target 75 mg twice daily. Over the first 2 weeks totalbinge-eating episodes dropped from 8 to 2 and from 4 days to 1 day per week. Sheceased having binge-eating episodes over her first 4 months of topiramate therapy. Herweight decreased from 109 to 98.6 kilograms (kg), and her body mass index dropped to38.5 kg/square meter. The only drug-induced side effect was somnolence at thebeginning of treatment (Appolinario et al, 2001).
N. NOCTURNAL EATING DISORDERS
- Topiramate improved symptoms of nocturnal
eating syndrome and sleep-related eating
a. Topiramate improved symptoms in 2 patients with NOCTURNAL EATINGSYNDROME (NES) and in 2 patients with SLEEP-RELATED EATING DISORDER(SRED). Topiramate was initiated at 25 milligrams (mg) nightly and was titrated to a
dose ranging from 100 to 400 mg nightly (mean dose 218.8 mg). All patients had a longhistory of symptoms (range 18 months to 31 years) that occurred nightly and 3 had triedmultiple therapies without benefit. Complete resolution in symptoms occurred in 1 NESpatient resulting in a 15 pound (lb) weight loss. The other NES patient decreasednocturnal eating to 1 night a week resulting in a 33 lb weight loss. One SRED patient haddecrease nocturnal eating to occasional episodes and lost 30 lb and the other SREDpatient decreased nocturnal eating to around 3 times a week with a resulting 20 lb weightloss. This effect has been maintained for a mean of 8.5 months. Upon dose reduction anddiscontinuation of therapy, symptoms have returned. Two patients had dose limiting sideeffects including reduction in sexual function and blepharospasm (Winkelman, 2003).
BUPROPION C. BULIMIA
- Bulimic patients may be unusually susceptible
to grand mal seizures while receiving bupropion
- Not to be used alone as treatment for bulimia
a. Oral bupropion 225 to 450 milligrams/day was reported effective in reducing episodesof binge eating and purging in non-depressed bulimic patients in a placebo-controlled,double-blind study (Horne et al, 1988). However, grand mal seizures were observed in 3of the 55 bupropion patients in this study. A fourth patient on placebo also experienced agrand mal seizure after bupropion was given in a subsequent open-label study with 14 ofthe placebo patients. Overall, 4 of 69 patients (5.8%) developed seizures while receivingbupropion. This incidence is much greater than that reported in previous clinical trialswhere bupropion was given in doses of 450 milligrams or less: 16 of 3,981 patients(0.4%).
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北 京 大 学 人 民 医 院 l ’s Hos t 3-year history of intermittent upper abdominal pain with jaundice. 3 years ago (Dec. 2006), the patient began to suffer from an upper abdominal pain, which would aggravateafter fat meal or drinking. The pain would radiate to the back, with no hiccup or acid regurgitation. At thesame time jaundice was found both in sclera and skin, accompani
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