Topamax(topiramate) Research and Weight Loss and Binge Eating and DiabetesTopamax -topiramate is being used off label(not approved by FDA yet) for many uses. This person is on Topamax -topiramate for bipolar disorder as a mood stabilizer but have noticed a real decline in sugar craving and decrease in binge eating and general appetite since I have been on Topamax. Many people with bipolar disorder have "cocktails" for medication -antidepressants, mood stabilizers, sleep aids, and anti anxiety and atypical antipychotics drugs. Some of these induce weight gain so Topamax is most welcome.
Now for the research on Topamax:
On June 14th at the 63rd Scientific Sessions of the American Diabetes Association, there was a discussion of topiramate and weight loss. Discussion was made of unexpected finding in past research of diabetics who had 15 to 16 percent weight loss after a 44 week follow up compared to 9 percent of the placebo group in an experiment investigating diabetic neuropathy.
Aaron I. Vinik, MD, PhD, director of the Strelitz Diabetes Research Institutes at Eastern Virginia Medical School, in Norfolk, Virginia who is investigating topiramate and diabetes said "This is the first time that anyone has seen a reduction in weight that persists for 16 months to 18 months, and the first time that any drug in addition to a low-calories diet results in long-term weight reduction" Johnson and Johnson had ended the study prematurely because of side effects but Vinik says his own research suggests lower doses might work and reduce the risk of side effects.
I don't know if it was mentioned how many non diabetic users of topamax have as many side effects as it is a widely used medication, ie this writer is on it for bipolar II without side effects and so many are on it for epilepsy.
At the same conference, Dr. Vinik discussed findings that topiramate in a small study of type II diabetes, improves symptoms and markers to neuropathy, damage to the nerves that produce pain, predisposes a person to amputation, and impairs heat and pain perception, besides other components of diabetes.
Recently there was a research study suggesting that Topamax may also help in reducing urge to drink alcohol. Remarkably, all 150 patients were enrolled into this clinical trial while they were still drinking heavily," said Professor Bankhole Johnson, chief of the Center's division of alcohol and drug addiction."Patients who took topiramate were six times more likely than those who received placebo to be continuously abstinent for at least one month during the three month trial.
"The researchers said topiramate may combat craving by inhibiting alcohol-induced release of dopamine in the brain. Dopamine is believed to be associated with many types of addictive behaviors"
"Over the same period, those taking the placebo were four times more likely to drink heavily for an entire month during the trial," Johnson added in a statement
Expert Opin Investig Drugs. 2003 Aug;12(8):1441-3. :
Academy for Eating Disorders International Conference on Eating Disorders. Denver, CO, USA, May 29-31, 2003.
Kaplan AS.
Loretta Anne Rogers Chair in Eating Disorders, Toronto General Hospital, 8-Eaton, Room 231, 200 Elizabeth Street, Toronto, Ontario, Canada.
allan.kaplan@uhn.on.ca
The focus of this meeting was the interface between eating disorders and obesity. A symposium at this meeting dealt with advances in treatment for bulimia nervosa (BN) and binge eating disorder. There were two presentations in this symposium that addressed pharmacological treatments. One reviewed drug treatments for BN, which included reviewing the evidence for the efficacy of tricyclic antidepressants, monoamine oxidase inhibitors and selective serotonin inhibitors in the treatment of BN. All drug studies demonstrated greater reduction in binge eating and purging than with placebo. Other medications studied without evidence of efficacy for BN include opiate antagonists, lithium and anticonvulsants. Two promising agents for BN that require further study are odansitron and topiramate. For binge eating disorder, studies have examined the efficacy of antidepressants (tricyclic antidepressants, selective serotonin re-uptake inhibitors and serotonin/noradrenaline re-uptake inhibitors), antiobesity agents (sibutramine) and antiepileptics associated with weight loss (topiramate), with some evidence of efficacy for these agents.
World J Biol Psychiatry. 2003 Oct;4(4):172-6. :
Adjunctive topiramate in bipolar II disorder.
Vieta E, Sanchez-Moreno J, Goikolea JM, Torrent C, Benabarre A, Colom F, Martinez-Aran A, Reinares M, Comes M, Corbella B.
Bipolar Disorders Programme, Barcelona Stanley Research Medical Institute, Centre Hospital Clinic, University of Barcelona, Barcelona, Spain.
evieta@clinic.ub.es
We evaluated the efficacy and safety of adjunctive topiramate in bipolar II patients who were either treatment-resistant to or unable to tolerate lithium, carbamazepine or valproate. Nineteen DSM-IV bipolar II patients received increasing doses of open-label topiramate as adjunctive therapy for their hypomanic (n=15) or depressive (n=4) symptoms. Sixteen patients completed the 12-week follow-up. There were highly significant improvements in YMRS, HDRS and CGI-BP-M scores (p=0.0001). Of the fifteen hypomanic patients, eight (53%) were rated as responders to topiramate (50% reduction in YMRS scores), and five (33%) met criteria for remission (YMRS score pound 8). Two of the four patients with a depressive episode at study entry (50%) were rated as responders (50% reduction in HDRS score), and one (25%) achieved remission (HDRS score pound 6). Topiramate was generally well tolerated.
One third of the patients experienced weight loss. These preliminary results suggest that adjunctive topiramate may be useful in treating bipolar II disorder..
1: Expert Opin Investig Drugs. 2003 Aug;12(8):1441-3. :
Academy for Eating Disorders International Conference on Eating Disorders. Denver, CO, USA, May 29-31, 2003.
Kaplan AS.
Loretta Anne Rogers Chair in Eating Disorders, Toronto General Hospital, 8-Eaton, Room 231, 200 Elizabeth Street, Toronto, Ontario, Canada.
allan.kaplan@uhn.on.ca
The focus of this meeting was the interface between eating disorders and obesity. A symposium at this meeting dealt with advances in treatment for bulimia nervosa (BN) and binge eating disorder. There were two presentations in this symposium that addressed pharmacological treatments. One reviewed drug treatments for BN, which included reviewing the evidence for the efficacy of tricyclic antidepressants, monoamine oxidase inhibitors and selective serotonin inhibitors in the treatment of BN. All drug studies demonstrated greater reduction in binge eating and purging than with placebo. Other medications studied without evidence of efficacy for BN include opiate antagonists, lithium and anticonvulsants. Two promising agents for BN that require further study are odansitron and topiramate. For binge eating disorder, studies have examined the efficacy of antidepressants (tricyclic antidepressants, selective serotonin re-uptake inhibitors and serotonin/noradrenaline re-uptake inhibitors), antiobesity agents (sibutramine) and antiepileptics associated with weight loss (topiramate), with some evidence of efficacy for these agents.
Neuropsychopharmacology. 2003 Jul;28(7):1292-9. Epub 2003 Apr 09.:
Topiramate normalizes hippocampal NPY-LI in flinders sensitive line 'depressed' rats and upregulates NPY, galanin, and CRH-LI in the hypothalamus: implications for mood-stabilizing and weight loss-inducing effects.
Husum H, Van Kammen D, Termeer E, Bolwig G, Mathe A.
Department of Physiology and Pharmacology, Division of Pharmacology, Institution of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Topiramate is currently used in the treatment of epilepsy, but this anticonvulsant drug has also been reported to exert mood-stabilizing effects and induce weight loss in patients. Neuropeptide Y (NPY) is abundantly and widely distributed in the mammalian central nervous system and centrally administered NPY markedly reduces pharmacologically induced seizures and induces antidepressant-like activity as well as feeding behavior. Two other peptides, galanin and corticotropin-releasing hormone (CRH), have also been proposed to play a modulatory role in mood, appetite, and seizure regulation. Consequently, we investigated the effects of single and repeated topiramate (10 days, once daily: 40 mg/kg i.p.) or vehicle treatment in 'depressed' flinders sensitive line (FSL) and control Flinders resistant line (FRL) rats on brain regional peptide concentrations of NPY, galanin, and CRH. The handling associated with repeated injections reduced hippocampal levels of NPY- and galanin-like immunoreactivities (LI) while NPY- and CRH-LI levels were increased in the hypothalamus, regardless of strain or treatment. In the hippocampus, concentrations of NPY-LI, galanin-LI, and CRH-LI were lower in FSL than FRL animals. Repeated topiramate treatment selectively normalized NPY-LI in this region in the FSL animals. In the hypothalamus, galanin-LI was reduced in FSL compared to FRL animals. Topiramate elevated the hypothalamic concentrations of NPY-LI, CRH-LI, and galanin-LI in both strains. Furthermore, topiramate elevated serum leptin but not corticosterone levels. The present findings show that topiramate has distinct effects on abnormal hippocampal levels of NPY, with possible implications for its anticonvulsant and mood-stabilizing effects. Furthermore, stimulating hypothalamic NPY-LI, CRH-LI and galanin-LI as well as serum leptin levels may be associated with the weight loss-inducing effects of topiramate.
Pharmacopsychiatry. 2004 Jan;37(1):37-40. :
Effects of topiramate in the treatment of alcohol dependence.
Rubio G, Ponce G, Jimenez-Arriero MA, Palomo T, Manzanares J, Ferre F.
Departamento de Psiquiatria y Salud Mental, Madrid, Spain.
garuva@inicia.es
BACKGROUND: Anticonvulsant drugs have been used in the treatment of alcohol addiction with relatively good results. The purpose of the present study was to evaluate tolerance and safety of topiramate in patients presenting alcohol dependence. METHODS: We studied 24 patients that fulfilled alcohol-dependence criteria (DSM-IV) and presented other psychiatric disorders for which the use of topiramate was indicated. During the 12 weeks of the study, the patients received topiramate (262 mg/day) plus the psychoactive drugs they were taking for the other disorders. Carbohydrate-deficient transferrin (CDT) values and measures of craving and alcohol use were taken every 2 weeks. RESULTS: Baseline rating of amount and frequency of craving and alcohol use decreased significantly by week 2, and CDT values decreased from week 6. Topiramate was well tolerated, and there were only three dropouts due to adverse events. CONCLUSION: Topiramate is safe and well tolerated, and may be beneficial in the treatment of alcohol dependence. A placebo-controlled study would be of interest.
Dermatol Online J. 2003 Dec;9(5):3. :
Evaluation of open-label topiramate for scar therapy.
Shapira NA, Lessig M, Murphy TK, Annis AM, Lazoritz M.
Department of Psychiatry, College of Medicine and the Evelyn F. and William McKnight Brain Institute, University of Florida, Gainesville, USA.
shapira@psychiatry.ufl.edu
A 3-month open-label pilot study was carried out to assess the safety, tolerability, and effect of the antiepilectic topiramate on the cosmetic appearance of scars. Ten adult subjects with discolored or raised scars at least 2 years old were given an oral dosage of 15 mg per day of topiramate for 1 month. The dosage was then increased to 30 mg per day if there was minimal or no improvement. The safety of topiramate was assessed in this study by reviewing adverse events and vital signs. Efficacy outcomes included a Clinician Global Impression Scale (CGI) to document changes such as thickness and color. Digital photos were taken with consistent variables. In addition, two independent medical reviewers blindly reviewed the photos. The Rosenberg Self-Esteem Scale was done at each visit to measure patients' levels of self-esteem. Side effects were generally mild with the most common being language problems (n = 3) and sleep disturbances (n = 3). All subjects completed the study and experienced at least minimal thinning and decreased coloration (usually redness) of their scars. Based on CGI-assessment data at 3 months, two subjects were very much improved, four were much improved, and four had minimal improvement. One independent medical reviewer arranged before and after treatment picture sets for ten out of ten subjects. The other independent medical reviewer arranged before and after treatment pictures sets for nine out of ten subjects (both p-values less than 0.025). The data indicate that topiramate may be a safe and effective treatment for scar therapy.
Ann Pharmacother. 2004 May;38(5):887-91. Epub 2004 Mar 23. : Links
Weight gain mitigation with topiramate in mood disorders.
Woods TM, Eichner SF, Franks AS.
School of Pharmacy, College of Health Sciences, University of Wyoming, Laramie, WY.
OBJECTIVE: To review the evidence of weight loss with use of topiramate in patients with mood disorders. DATA SOURCES: Literature search included MEDLINE (1966-December 2003), International Pharmaceutical Abstracts (1970-December 2003), and EMBASE (1980-December 2003). Search terms included topiramate, weight loss, adverse effect, mood disorders, bipolar disorder. DATA SYNTHESIS: Weight gain is a common adverse effect of many agents used to treat mood disorders. Topiramate has been evaluated in the management of some mood disorders, and weight loss may be a beneficial side effect in these patients. Case reports, letters to the editor, prospective investigations, and retrospective observational studies were reviewed to identify evidence of weight loss with topiramate use in patients with mood disorders. CONCLUSIONS: Current evidence suggests an association between topiramate and weight loss. Based on the limited data, controlled studies need to be conducted to define the role of topiramate in patients with mood disorders who would also benefit from weight reduction.
1: Sleep Med. 2003 May;4(3):243-6. :
Treatment of nocturnal eating syndrome and sleep-related eating disorder with topiramate.
Winkelman JW.
Divisions of Psychiatry and Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02459, USA.
jwinkelman@sleephealth.com
BACKGROUND: Sleep-related eating disorder (SRED) and nocturnal eating syndrome (NES) combine features of sleep disorders and eating disorders. Treatment of these nocturnal eating behaviors has been directed towards underlying identifiable sleep or eating disorders using dopaminergic or opioid agonists, as well as anorectic agents, at times with the addition of sedatives. METHODS: Two patients with SRED and two with NES, who had failed multiple previous trials of pharmacotherapy and psychotherapy, were treated in a naturalistic, open-label fashion with topiramate at night. Reduction in nocturnal eating was graded based on self-report. Weight was computed at the outset of, and during, topiramate treatment. RESULTS: One patient with NES had a complete elimination of nocturnal eating with topiramate, two patients (one with NES, one with SRED) had a marked response, and one patient (with SRED) had a moderate response. Mean dose was 218 mg, though three patients noted an improvement at 100 mg. Notable weight loss was observed in all patients (mean of 11.1 kg). Benefits of topiramate treatment have been maintained for a mean period of 8.5 months. CONCLUSIONS: Topiramate may be of benefit for patients with NES or SRED in reducing nocturnal eating, improving nocturnal sleep, and producing weight loss.
Obes Res. 2003 Apr;11(4):556-62. :
Predictors of weight loss in adults with topiramate-treated epilepsy.
Ben-Menachem E, Axelsen M, Johanson EH, Stagge A, Smith U.
Sahlgrenska Academy at Goteborg University, Goteborg, Sweden.
ebm@neuro.gu.se
OBJECTIVE: We examined predictors of weight loss with topiramate, an anticonvulsant associated with weight loss in adults. RESEARCH METHODS AND PROCEDURES: In this uncontrolled, prospective clinical trial, topiramate was added to existing anticonvulsants in adults (40 to 110 kg) with partial-onset seizures. Primary measurements were change from baseline weight after 3 months and 1 year in patients completing 1 year of topiramate treatment (N = 38). Physiological and metabolic measures were analyzed for correlation with weight loss during topiramate treatment. RESULTS: In patients who completed 1 year of topiramate treatment, baseline weight was reduced in 82% at 3 months and in 86% at 1 year. Mean body weight was reduced 3.0 kg (3.9% of baseline) at 3 months and 5.9 kg (7.3%) at 1 year. In obese patients [body mass index (BMI) >/= 30 kg/m(2)], mean weight loss was 4.2 kg (4.3%) at 3 months and 10.9 kg (11.0%) at 1 year. Weight loss was primarily caused by reduction in body fat mass. For all patients, weight loss at 3 months correlated most strongly with reduced caloric intake (p = 0.02). At 1 year, caloric intake had returned to baseline levels; weight loss correlated most strongly with higher baseline BMI (p = 0.0007). DISCUSSION: Our results suggest that weight loss occurs in most adults treated with topiramate and is sustained for at least 1 year. Reduced caloric intake may account, in part, for weight loss during early treatment. The pattern of weight loss differs according to baseline BMI, with obese patients experiencing greater weight loss during continued therapy.
1: J Clin Psychiatry. 2003 May;64(5):532-9. :
Safety of available agents used to treat bipolar disorder: focus on weight gain.
Nemeroff CB.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
cnemero@emory.edu
BACKGROUND: Pharmacotherapeutic management of bipolar disorder has advanced considerably since the introduction of lithium therapy nearly 50 years ago. The sizable percentage of patients who do not respond adequately to lithium and/or are intolerant to its side effects has served as an impetus for identifying alternative pharmacotherapeutic agents. Recent advances in the understanding of the neurotransmitter systems and their receptors as it applies to treatment of bipolar disorder has, in part, led to progress in delineating applications of anticonvulsant/antiepileptic drugs (AEDs) in this area. Although the efficacy of many drugs has been evaluated in patients with this disorder, medication tolerability and adherence issues related to unfavorable side effect profiles are substantial impediments to the development of novel pharmacotherapies. The potential for excessive weight gain as a side effect of certain psychopharmacologic agents remains a concern to both clinicians and patients. METHOD: English-language literature from 1985-2001 in MEDLINE was searched for the terms bipolar disorder, anticonvulsant, antiepileptic, lithium, antipsychotic, weight, and compliance. This article reviewed current therapeutic options for bipolar disorder, including newer AEDs and atypical antipsychotic drugs, with emphasis on the issue of weight gain and possible approaches to minimizing this risk. RESULTS: Certain newer AEDs are characterized by more favorable safety and tolerability profiles that include weight loss as a desirable side effect. Because bipolar disorder is associated with unacceptably high rates of relapse, recurrence, and morbidity, the concept of pharmacotherapeutic efficacy logically not only includes symptom relief but also necessarily encompasses issues related to regimen tolerability and adherence. CONCLUSION: There is a need for guidelines to help physicians carefully formulate and individualize management plans to reach safe, effective, and cost-efficient patient outcomes. Monitoring the weight of patients with bipolar disorder and educating them regarding this issue should be standard components of any treatment plan.
PSYCHIATRY PROFESSOR AUTHORS ARTICLE ABOUT OVEREATING
"McElroy said that researchers are unsure of how the drugs controlled the hunger of patients. "One theory is they block glutamate in the brain," she said. "Glutamate is a neurotransmitter that promotes eating behavior""Binge eating is often related to mood dysregulation - be it depression or mood swings," said McElroy. "Topiramate and zonisamide reduce the urge to binge, restore normal satiety (feeling full after eating) and may also help 'normalize' or 'stabilize' mood. The more stable a person's mood is, the more in control his/her eating is likely to be."
"These medications also appear affective for obesity without binge eating or bulimia," she added. "They're probably eating more than they 'need,' but they are not out of control."
"Another fascinating story concerning startle response and topamax
Psychopharmacology (Berl). 2003 Oct 30 [Epub ahead of print]. :
Topiramate attenuates exaggerated acoustic startle in an animal model of PTSD.
Khan S, Liberzon I.
Department of Psychiatry, University of Michigan, 1500 E Medical Center Drive, MI 48109, Ann Arbor, USA.
RATIONALE. Exaggerated acoustic startle is a prominent symptom of post-traumatic stress disorder (PTSD); however, its physiological basis is not well understood, and there are few available treatments. Neurobiological research has suggested that anti-kindling agents and/or glutamate antagonists can attenuate the acoustic startle response (ASR) in animal models. The anticonvulsant topiramate is an AMPA antagonist that also demonstrates potent anti-kindling effects and may, therefore, have promise in treating trauma-enhanced ASR. OBJECTIVE. To evaluate the ability of topiramate to attenuate stress-induced increases in ASR in a previously validated animal model of PTSD. METHODS. Male Sprague-Dawley rats ( n=36) served as controls or received single prolonged stress (SPS). SPS consisted of 2 h restraint, forced swim and ether anesthesia, then a 7-day "undisturbed" period. Animals then received vehicle, 10 mg/kg or 30 mg/kg of topiramate orally, twice daily for 7 days. ASR was assessed for all animals before and after the study, in light and dark environments. RESULTS. SPS produced a sustained increase in the ASR in both environments, an effect that was significantly reduced by topiramate. Meanwhile the ASR of control animals remained unaffected by topiramate. CONCLUSIONS. The current results provide one of the few demonstrations of a single stress episode producing sustained enhancement of ASR. In addition, topiramate demonstrates promise in treating exaggerated acoustic startle symptoms in PTSD or other stress-related disorders.
In JAMA 2003;289:14:1820-1825,zonisamide, another anticonvulsant is suggested through prelimary research to also have properties that may contribute to weight loss. Research is also ongoing for zonisamide in treating bipolar disorder.
JAMA 2003 Apr 9;289(14):1820-5:
Zonisamide for weight loss in obese adults: a randomized controlled trial.
Gadde KM, Franciscy DM, Wagner HR 2nd, Krishnan KR.
Obesity Clinical Trials Program, Department of Psychiatry, Duke University Medical Center, Durham, NC.
CONTEXT: Zonisamide is a marketed antiepileptic drug that has serotonergic and dopaminergic activity in addition to blockade of sodium and calcium channels. Weight loss was an adverse effect associated with zonisamide treatment in epilepsy clinical trials. OBJECTIVE: To evaluate the efficacy of zonisamide for weight loss in obese adults. DESIGN AND SETTING: Sixteen-week randomized, double-blind, placebo-controlled trial with an optional single-blind extension of the same treatment for another 16 weeks, conducted at Duke University Medical Center from March 2001 to March 2002. PARTICIPANTS: Fifty-five (92%) women and 5 (8%) men (mean [SE] body mass index, 36.3 [0.5]; mean age, 37.0 (1.0) years). INTERVENTIONS: Patients were randomly assigned to receive zonisamide (n = 30) or placebo (n = 30). All participants were prescribed a balanced hypocaloric diet (500 kcal/d deficit) and compliance was monitored with self-rated food diaries. Zonisamide therapy was started at 100 mg/d orally, with gradual increase to 400 mg/d and further increase to 600 mg/d for patients losing less than 5% of body weight at the end of 12 weeks. Placebo dosing was identical. MAIN OUTCOME MEASURE: Change in body weight. RESULTS: Of the 60 randomized patients, 51 completed the 16-week acute phase. In an intent-to-treat analysis using the available data for all randomized participants with the last observation carried forward, the zonisamide group lost more body weight than the placebo group (mean [SE], 5.9 [0.8] kg [6.0% loss] vs 0.9 [0.4] kg [1.0% loss]; t = 5.5; P<.001) during the 16-week period. A longitudinal mixed-model regression for weight change controlling for age, race, sex, body mass index, and percent body fat estimated that zonisamide treatment over the 16-week study duration was associated with significantly greater weight loss than was placebo (t = 6.4; P<.001). Seventeen (57%) of 30 in the zonisamide group and 3 (10%) of 30 in the placebo group lost at least 5% of body weight (P<.001) by week 16. Of the 37 participants who entered the extension phase, 36 completed week 32. The zonisamide group (n = 19) had a mean weight loss of 9.2 kg (1.7 kg) (9.4% loss) at week 32 compared with 1.5 kg (0.7 kg) (1.8% loss) for the placebo group (n = 17) (t = 4.0; P<.001). Zonisamide was tolerated well, with few adverse effects. CONCLUSION: In this short-term, preliminary trial, zonisamide and hypocaloric diet resulted in more weight loss than placebo and hypocaloric diet in the treatment of obesity.
Lancet 2003 May 17;361(9370):1677-85 :
Oral topiramate for treatment of alcohol dependence: a randomised controlled trial.
Johnson BA, Ait-Daoud N, Bowden CL, DiClemente CC, Roache JD, Lawson K, Javors MA, Ma JZ.
Department of Psychiatry, University of Texas Health Science Center at, San Antonio, TX, USA
Background Topiramate, a sulphamate fructopyranose derivative, might antagonise alcohol's rewarding effects associated with abuse liability by inhibiting mesocorticolimbic dopamine release via the contemporaneous facilitation of gamma-amino-butyric acid activity and inhibition of glutamate function. We aimed to see whether topiramate was more effective than placebo as a treatment for alcohol dependence.Methods We did a double-blind randomised controlled 12-week clinical trial comparing oral topiramate and placebo for treatment of 150 individuals with alcohol dependence. Of these 150 individuals, 75 were assigned to receive topiramate (escalating dose of 25-300 mg per day) and 75 had placebo as an adjunct to weekly standardised medication compliance management. Primary efficacy variables were: self-reported drinking (drinks per day, drinks per drinking day, percentage of heavy drinking days, percentage of days abstinent) and plasma gamma-glutamyl transferase, an objective index of alcohol consumption. The secondary efficacy variable was self-reported craving.Findings At study end, participants on topiramate, compared with those on placebo, had 2.88 (95% CI -4.50 to -1.27) fewer drinks per day (p=0.0006), 3.10 (-4.88 to -1.31) fewer drinks per drinking day (p=0.0009), 27.6% fewer heavy drinking days (p=0.0003), 26.2% more days abstinent (p=0.0003), and a log plasma gamma-glutamyl transferase ratio of 0.07 (-0.11 to -0.02) less (p=0.0046). Topiramate-induced differences in craving were also significantly greater than those of placebo, of similar magnitude to the self-reported drinking changes, and highly correlated with them.Interpretation Topiramate (up to 300 mg per day) is more efficacious than placebo as an adjunct to standardised medication compliance management in treatment of alcohol dependence.
Am J Psychiatry 2003 Feb;160(2):255-61
:
Topiramate in the treatment of binge eating disorder associated
with obesity: a randomized, placebo-controlled trial.
McElroy SL, Arnold LM, Shapira NA, Keck PE Jr, Rosenthal NR, Karim
MR, Kamin M, Hudson JI.
OBJECTIVE: Binge eating disorder is associated with obesity. Topiramate is an
antiepileptic agent associated with weight loss. The objective of this study was
to evaluate topiramate in the treatment of binge eating disorder associated with
obesity. METHOD: For this 14-week, double-blind, flexible-dose (25-600
mg/day) topiramate trial, 61 outpatients (53 women, eight men) with binge
eating disorder who were obese (body mass index >/=30 kg/m(2)) were
randomly assigned to receive topiramate (N=30) or placebo (N=31). The
primary efficacy measure was binge frequency. The primary analysis of
efficacy was a repeated-measures random regression with treatment-by-time as
the effect measure. RESULTS: Compared with placebo, topiramate was
associated with a significantly greater rate of reduction in binge frequency,
binge day frequency, body mass index, weight, and scores on the Clinical Global
Impression severity scale and the Yale-Brown Obsessive Compulsive Scale
(modified for binge eating). Topiramate was also associated with significantly
greater reductions in binge frequency (topiramate: 94%, placebo: 46%) and
binge day frequency (topiramate: 93%, placebo: 46%) and with a significantly
higher level of response than placebo. The mean weight loss for
topiramate-treated subjects who completed the study was 5.9 kg. Median
topiramate dose was 212 mg/day (range=50-600). Nine patients (three
receiving placebo, six given topiramate) discontinued because of adverse events.
The most common reasons for discontinuing topiramate were headache (N=3) and
paresthesias (N=2). CONCLUSIONS: Topiramate was efficacious and
relatively well tolerated in the short-term treatment of binge eating disorder
associated with obesity.
Use of topiramate in treatment-resistant bipolar spectrum
disorders.
To evaluate the effectiveness and safety of topiramate as add-on, long-term
therapy for treatment-resistant bipolar-spectrum disorders, 34 DSM-IV
bipolar-spectrum patients, including bipolar I (n = 28), bipolar II (n = 3),
bipolar not otherwise specified (n = 2), and schizoaffective disorder bipolar
type (n = 1), considered to be resistant to treatment with lithium,
carbamazepine, and valproate, received increasing doses of topiramate as
adjunctive therapy for their manic (n = 17), depressive (n = 11), hypomanic (n =
3), or mixed (n = 3) symptoms. Outcome measures included the Young Mania
Rating Scale (YMRS), the Hamilton Rating Scale for Depression (HAM-D),
and the Clinical Global Impression (CGI) for Severity. Patients were followed
up for 6 months. Twenty-five patients (74%) completed the 6-month
follow-up. Nine patients (26%) dropped out early due to lost of follow-up (n
= 4), worsening of symptoms (n = 2), side effects (n = 1), hospitalization due to
intercurrent illness (n = 1), and noncompliance (n = 1). By intent-to-treat
analysis, there was a significant reduction in YMRS, HAM-D, and CGI scores
(p < 0.0001 for all measures at the endpoint) after the introduction of
topiramate. Most therapeutic effects appeared between weeks 2 and 6.
Fifty-nine percent of manic patients and 55% of depressed patients were
considered to be responders to the drug, which was well tolerated; only one
patient discontinued due to side effects. The most common side effect was
paraesthesia (n = 2). Ten patients experienced moderate weight loss during
the follow-up period. The mean topiramate dose at endpoint was 202 +/- 65
mg/day. These preliminary results indicate that adjunctive topiramate may be
useful in the long-term treatment of bipolar spectrum disorders, even in the
most difficult-to-treat patients.
Topiramate use in obese patients with binge eating disorder: an
open study
OBJECTIVE: To assess topiramate's efficacy and tolerability in a group of
obese binge eaters with no neuropsychiatric comorbidity. METHOD: We
consecutively selected 8 obese patients with binge eating disorder (BED) and
no medical or psychiatric comorbidity from individuals seeking treatment for
obesity. Treatment with topiramate at 150 mg daily was administered over a
16-week period. To assess outcome, we employed the days with binge episodes
per week (DBE), the Binge Eating Scale (BES), the Beck Depression Inventory
(BDI), and body weight evaluation. RESULTS: Of the 6 patients who
completed the trial, all showed reduced binge eating. Four patients presented
a total remission, and 2 had a marked reduction in binge eating frequency. The
mean DBE decreased significantly from 4.3 to 1.1 (P = 0.03), as did the BES
scores, which fell from 31.8 to 15.3 (P = 0.04). Moreover, there was a
statistically significant weight loss (mean 4.1 kg, P = 0.04). The most frequent
side effects were paresthesias, fatigue, and somnolence. CONCLUSION:
Topiramate may be an effective and well-tolerated agent in the treatment of
BED in obese patients.
Third generation anticonvulsants in bipolar disorder: a review of
efficacy and summary of clinical recommendations.
BACKGROUND: To review the literature on efficacy of third generation
anticonvulsants for treatment of bipolar disorder and provide clinical
recommendations. METHOD: Open and controlled studies, case reports, and
case series on the efficacy of lamotrigine, gabapentin, topiramate, tiagabine,
and zonisamide were located through electronic searches of several databases,
by manual search of proceedings of international meetings, and through
contacting authors of recent reports. RESULTS: Lamotrigine is the best
studied anticonvulsant and has efficacy in acute bipolar depression and in
longer term treatment of bipolar depression as well as rapid-cycling bipolar
II disorder but not in acute mania. Open reports suggest usefulness of
gabapentin as an adjunct in bipolar disorder, but double-blind trials failed to
confirm efficacy in acute mania and treatment-resistant rapid-cycling bipolar
disorder. Topiramate is reported to be effective in acute mania and
rapid-cycling bipolar disorder in several open studies, but methodological
problems in a double-blind study led to a failed study in acute mania.
However, topiramate may lead to weight loss in some patients. Zonisamide
deserves further investigation, but tiagabine does not appear to be useful in
acute mania. CONCLUSION: Lamotrigine clearly fills an unmet need in
treating bipolar depression and rapid-cycling bipolar disorder. Other third
generation anticonvulsants with the exception of tiagabine offer promise but
require confirmation of their efficacy from double-blind studies.
Is topiramate effective for weight loss in neuroleptic-induced
obesity? 2 case reports
OBJECTIVES: Topiramate, a fairly new anticonvulsant, is increasingly being
used as a mood stabilizer in bipolar and schizoaffective disorders. One
common side effect is a reduced appetite that often results in weight loss.
This finding raises the interesting question of whether both mood and body
weight can be stabilized in patients who have gained weight while being
treated with neuroleptics for one of the disorders mentioned above.
METHODS: We studied the body weight, subjective sense of well-being, and
psychopathology in two adolescent patients who were being treated with
topiramate (alone or in combination with a neuroleptic drug). Both patients
had reduced appetite, while body weight either remained stable or was
reduced. RESULTS: The patients reported both improved control of food
intake and mood stabilization. CONCLUSIONS: We conclude that
adolescents with affective disturbance who have gained weight on neuroleptic
drugs may benefit from topiramate in terms of mood stabilization and body
weight control.
Long-term effects of topiramate on bipolar mood instability,
weight change and glycemic control: a case-series
Topiramate is an antiepileptic agent, which is being investigated as a
mood-stabilizer. Three obese individuals with DSM-IV bipolar I disorder and
type II diabetes mellitus received topiramate treatment in combination with
antipsychotics and valproate or carbamazepine. In addition to improved mood
stability, these individuals lost between 16 to 20.5% of their pre-topiramate
body weight and also achieved significant glycemic control.
