Topiramate Group Research Articles

Topiramate for the Treatment of Methamphetamine Addiction: A Meta-Analysis

Methamphetamine (MAP) is one of the most abused recreational drug worldwide and its abuse creates a socioeconomic burden for developed and developing countries alike. It is hypothesized to act on various receptors to facilitate the release of catecholamines such as dopamine to provide a euphoric effect. As of date, there are no pharmacologic interventions approved yet for the treatment of MAP addiction. Topiramate is an anti-epileptic drug that works on multiple pathways to modulate other catecholamines such as gamma-aminobutyric acid (GABA) to decrease the reinforcing effects of stimulants like MAP. Two randomized controlled trials done by Elkashef et al. and Razeai et al. investigated the effectiveness of topiramate in the treatment of MAP addiction. To the authors knowledge, this is the first meta-analysis on topiramate for methamphetamine addiction. This study aims to evaluate the effectiveness of topiramate in the treatment of methamphetamine addiction among diagnoses methamphetamine dependents. Randomized controlled trials were searched through PubMed and other databases. Fixed variant analysis was applied to compare dichotomous outcomes. Two randomized controlled trials comparing maximum topiramate dose tolerated and placebo were included. The primary outcome was negative MAP use using urine test on the 10th week of study. There was no significant difference between the topiramate and placebo groups (RR 1.03, 95% CI [0.85,1.26], p=0.73). There is insufficient evidence to show that topiramate significantly promotes MAP abstinence on MAP abusers compared to placebo. Due to paucity of controlled studies, firm recommendation for its routine use for MAP addiction cannot be established.

Identification of Novel Signal Transduction, Immune Function, and Oxidative Stress Genes and Pathways by Topiramate for Treatment of Methamphetamine Dependence Based on Secondary Outcomes.

Topiramate (TPM) is suggested to be a promising medication for treatment of methamphetamine (METH) dependence, but the molecular basis remains to be elucidated. Among 140 METH-dependent participants randomly assigned to receive either TPM (N = 69) or placebo (N = 71) in a previously conducted randomized controlled trial, 50 TPM- and 49 placebo-treated participants had a total 212 RNA samples available at baseline, week 8, and week 12 time points. Following our primary analysis of gene expression data, we reanalyzed the microarray expression data based on a latent class analysis of binary secondary outcomes during weeks 1-12 that provided a classification of 21 responders and 31 non-responders with consistent responses at both time points. Based on secondary outcomes, 1,381, 576, 905, and 711 differentially expressed genes at nominal P values < 0.05 were identified in responders versus non-responders for week 8 TPM, week 8 placebo, week 12 TPM, and week 12 placebo groups, respectively. Among 1,381 genes identified in week 8 TPM responders, 359 genes were identified in both week 8 and week 12 TPM groups, of which 300 genes were exclusively detected in TPM responders. Of them, 32 genes had nominal P values < 5 × 10-3 at either week 8 or week 12 and false discovery rates < 0.15 at both time points with consistent directions of gene expression changes, which include GABARAPL1, GPR155, and IL15RA in GABA receptor signaling that represent direct targets for TPM. Analyses of these 300 genes revealed 7 enriched pathways belonging to neuronal function/synaptic plasticity, signal transduction, inflammation/immune function, and oxidative stress response categories. No pathways were enriched for 72 genes exclusively detected in both week 8 and week 12 placebo groups. This secondary analysis study of gene expression data from a TPM clinical trial not only yielded consistent results with those of primary analysis but also identified additional new genes and pathways on TPM response to METH addiction.

The investigation of the effects of topiramate on the hypothalamic levels of fat mass/obesity-associated protein and neuropeptide Y in obese female rats

Objective: The aim of the present study is to investigate the effects of topiramate on the fat mass/obesity-associated protein (FTO) and on the neuropeptide Y (NPY) level in the hypothalamus depending on the recently increased prevalence of obesity.Method: In this study, twenty-four female rats were divided into four equal groups: Non-obese control, obese control, non-obese topiramate, and obese topiramate. Obese groups were fed with a 40% high-fat diet. At the end of the 9th week, the drug treatment started and the subjects were treated with topiramate once a day for 6 weeks. All animals underwent cardiac perfusion under high-dose anesthesia on the 15th week. Tissues were analyzed using biochemical, histological, and stereological methods.Results: In terms of neuron number in the arcuate nucleus area, a significant difference was observed among all groups (P < 0.01). The neuron number of the non-obese topiramate group was found to be significantly higher than that of the non-obese control group (P < 0.01). In the examination of the ventromedial nucleus of the entire group, it was observed that the neuron number of the non-obese control group was significantly lower than those of the other groups (P < 0.01). A significant increase in the NPY levels of the obese groups compared to the groups treated with topiramate was observed. Furthermore, the amount of the FTO protein increased in obese rats, while FTO and NPY levels decreased in the groups treated with topiramate.Discussion: In conclusion, the mechanism of the effect of topiramate to create a state of obesity is thought to involve the decrease in the levels of NPY and FTO.

New Developments in the Prophylactic Drug Treatment of Pediatric Migraine: What Is New in 2017 and Where Does It Leave Us?

Headaches in children are quite common; however, the study and characterization of headache disorders in the pediatric age group has historically been limited. Because of the lack of controlled studies on prophylactic treatment of headache disorders in this age group, the diagnosis of migraine rests on criteria similar those in adults. Likewise, data from adult studies is often inferred and applied to children. Although it appears that many preventives are safe in children, currently none are FDA or EMA approved for this age group. Consequently, many children who present to their primary care physicians with migraines do not receive any preventive therapy despite experiencing significant disability. Controlled clinical trials investigating the use of preventive medications in children have suffered from high placebo response rates. The shorter duration of headaches and other characteristic features seen in children are such that designing randomized controlled trials in this age group is more problematic and limiting. Treatment practices vary widely, even among specialists, due to the absence of evidence-based guidelines from clinical trials. The Childhood and Adolescent Migraine Prevention Study (CHAMP) was developed to examine the effectiveness of two of the most widely prescribed preventive medications for pediatric migraine and help narrow this gap. To date, it has been the largest enrolling study of its kind within the pediatric migraine world; its results and implications will be discussed and considered here. The CHAMP trial was discontinued early on account of futility and exhibited that neither of two preventive medications for pediatric migraine was more effective than placebo in reducing the number of headache days over a period of 24weeks. Subjects in the amitriptyline and topiramate groups had higher rates of adverse events than those who had received placebo.

A Novel Therapy for cocaine dependence during abstinence: A randomized clinical trial.

BackgroundTopiramate is an anticonvulsant drug and an ideal candidate for reducing the craving in people relying on cocaine. Contingency management is one of the common therapies in the domain of addiction.ObjectiveThe present study aimed to evaluate and compare three medication methods of Topiramate (TPM), Contingency Management (CM) and the combined TPM treatment and cash intervention on craving during abstinence.MethodsThis randomized clinical trial was conducted at Bijan Center for Substance Abuse Treatment in Tehran, Iran, from December 15, 2014 to November 20, 2015. One hundred males (Age range=18–34; SD=4.11) undergoing abstinence were assigned randomly to four groups (n=25) of Topiramate (TPM), Contingency Management (CM) and the Combined Method plus a placebo control group. Treatment was provided for twelve weeks for the experiment groups, and only the control group received the placebo. Participants in the Cash-based and CM Condition had an identical 12-week escalating schedule of reinforcement (cash-based incentives worth $0, $20, $40, and $80). Also, in the Topiramate group, participants’ dosage ranged between 25–300 mg/day in escalating doses) 25, 50, 100, 150, 200, 250, 300). In addition, all subjects received brief behavioral compliance enhancement treatment (BBCET). Participants took a urine test twice a week, with a given threshold of > 300 ng/ml, and indicators of cocaine craving (response rate= 91%) was evaluated in two phases of pre-test and post-test. We used Chi square, ANCOVA Univariate Model and Scheffe’s post hoc to analyze the primary and secondary outcomes. Also, the qualitative data resulted from demographic evaluations were coded and analyzed by the instrument of analysis of qualitative data i.e. Atlas.ti, Version 5.2.ResultsThe results showed that all three types of treatment played a significant efficacy in reducing the craving. The mean (95% CI) scores of craving was 12.04 (p=0.05) with TPM, 13.89 (p=0.05) with CM, 10.92 (p=0.01) with Mix and 16.89 (p>0.05) with control. Moreover, the highest variance explaining the changes in craving was assigned to the combined treatment (p<0.01).ConclusionsThe findings of this study, while having applicable aspects in this domain, can be helpful in planning supplementary remedial procedures.Trial registrationThe trial was registered at the Thai Clinical Trial Registration Center with the TCR ID: TCTR20170112001.FundingThe authors received no financial support for the research, authorship, and/or publication of this article.

Screening of alcohol de-addiction potential of zinc: a study on albino rats

Background: With regard to tobacco and alcohol addiction, involvement of NMDA receptors and glutamate as neurotransmitter has been highlighted. Few indirect evidences support possible de-addiction potential of zinc being mediated through their interaction with nicotinic and NMDA receptors. The objectives of the present study were planned to analyze the alcohol de-addiction potential of oral zinc sulfate as a monotherapy and as a supplement to topiramate, in male wistar albino rats.Methods: Male wistar albino rats were exposed to ‘two-bottle free choice’ model of voluntary ethanol consumption, wherein each animal had access to water and 10% v/v ethyl alcohol in two separate bottles. Thirty male rats divided into five groups, each containing six rats were treated as control group, receiving 1ml/kg/d distilled water orally; zinc sulfate group receiving 18mg/kg/d of elemental zinc orally; topiramate group receiving topiramate 5mg/kg/d, orally and Topiaramate plus Zinc sulfate group receiving both zinc sulfate (18mg/kg/d) and topiramate (5mg/kg/d) orally for two weeks.Results: There were no significant differences with regard to all the three parameters in two-way ANOVA. However, there were significant differences with regard to amount of alcohol and water consumed but not API, in all the treatment groups in post-hoc test.Conclusions: It is unclear on to the alcohol de-addiction potential of zinc as monotherapy and combination therapy with topiramate.

Topiramate monotherapy for juvenile myoclonic epilepsy.

Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate monotherapy in people with JME. This is an updated version of the original Cochrane Review published in Issue 12, 2015. To evaluate the efficacy and tolerability of topiramate monotherapy in the treatment of JME. For the latest update, on 21 February 2017 we searched Cochrane Epilepsy's Specialized Register, CENTRAL, MEDLINE, and ClinicalTrials.gov. We also searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted study authors and pharmaceutical companies. We included randomized controlled trials (RCTs) investigating topiramate monotherapy versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders or experiencing adverse events (AEs). Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data. We included three studies with 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or more reduction in primarily generalized tonic-clonic seizures (PGTCS) compared with participants in the placebo group. There were no significant differences between topiramate versus valproate in participants responding with a 50% or more reduction in myoclonic seizures or in PGTCS or seizure-free. Concerning tolerability, we ranked AEDs associated with topiramate as moderate-to-severe, while we ranked 59% of AEDs linked to valproate as severe complaints. Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group. We judged the quality of the evidence from the studies to be very low. Since the last version of this review we found no new studies. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but there were no more benefits of efficacy in topiramate compared with valproate. In the future, well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.

Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine

BackgroundWhich medication, if any, to use to prevent the headache of pediatric migraine has not been established.MethodsWe conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headache-related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment.ResultsA total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between-group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P=0.26; topiramate vs. placebo, P=0.48; amitriptyline vs. topiramate, P=0.49). There were also no significant between-group differences in headache-related disability, headache days, or the percentage of patients who completed the 24-week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate group had a suicide attempt.ConclusionsThere were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events. (Funded by the National Institutes of Health; CHAMP ClinicalTrials.gov number, NCT01581281).

Topiramate and accommodation: Does topiramate cause accommodative dysfunction?

ObjectiveTo investigate the accommodation function in topiramate users. DesignCase-control clinical study. ParticipantsThe participants included 16 controls and 22 patients using 100 mg/kg topiramate who were diagnosed with migraine according to the International Classification of Headache Disorders, second edition criteria. MethodsOne-minute dynamic measurements of refraction with accommodation stimuli of 0 D, 2 D, 2.5 D, 3 D, 4 D, and 5 D were obtained using the open field refractometer WAM-5500 in. ResultsIn most of the accommodation stimuli ranges (0 D, 2.5 D, 3 D, and 5 D), topiramate users had a significantly higher accommodative lag compared with controls (p = 0.028, p = 0.014, p = 0.011, and p = 0.011, respectively). The most important causes of accommodative lag were found to be accommodation stimulus and inclusion in the topiramate group (p < 0.001, R2 = 0.32, 95% CI 0.22–0.37 and 0.42–0.91, respectively). Multivariate linear regression analysis revealed that the 2 most important predictors of accommodative lag were accommodation stimulus and age (p < 0.001, r = 0.51, 95% CI 0.31–0.32 and 0.67–0.69, respectively) ConclusionsEven after adjustment for age, accommodative lag is greater across several accommodative stimulus levels in patients using topiramate, which may be related to visual symptoms in topiramate users.

Meal replacements followed by topiramate for the treatment of adolescent severe obesity: A pilot randomized controlled trial.

To assess the safety and efficacy of short-term meal replacement therapy followed by topiramate for body mass index (BMI) reduction in adolescents with severe obesity. Adolescents (ages 12-18 years) with severe obesity (BMI ≥1.2 times the 95th percentile or BMI ≥35 kg/m2 ) were recruited for this double-blind, randomized, placebo-controlled trial. Participants completed 4 weeks of meal replacement therapy followed by randomization (1:1) to either 24 weeks of topiramate 75 mg/day or placebo. Mean changes were compared between groups. Thirty adolescents (mean age 15.2 ± 1.7 years, mean BMI 40.3 ± 4.6 kg/m2 ) completed the meal replacement phase and were randomized; 21 completed the study. The difference in mean percent change in BMI between the topiramate and placebo groups was not significant (-1.9%; 95% CI: -5.2% to +1.5%; P = 0.291). Significant improvements in visceral fat and very-low-density lipoprotein cholesterol were observed in the topiramate compared with the placebo group. There were no concerning changes in neurocognitive function or bone health. In this pilot study, 4 weeks of meal replacement therapy followed by 24 weeks of low-dose topiramate compared with meal replacement therapy alone did not result in significant BMI reduction for adolescents with severe obesity.

A Pilot Study of Randomized, Head-to-Head of Metformin Versus Topiramate in Obese People With Schizophrenia.

A number of research studies support the weight loss effects of metformin and topiramate for obese people with schizophrenia. However, only a few studies have addressed the sustainability of the body weight reduction after discontinuation of these drugs. Moreover, head-to-head studies are still lacking. The study aims to evaluate and compare the efficacy of metformin and topiramate in weight reduction and weight maintenance after discontinuation of these drugs in obese people with schizophrenia. Twenty-two obese inpatients with schizophrenia were recruited and randomized into the metformin group (n = 11; daily dose, 1000 mg) and the topiramate group (n = 11; daily dose, 100 mg). A head-to-head, fixed-dose, and single-blinded design was used. Ten obese patients with schizophrenia of similar sex as that of the treated group were included as the control group. After a 4-month treatment, the metformin group showed a body weight reduction of 3.8 kg, and the topiramate group showed a reduction of 2.7 kg. However, the reduction could be sustained only in the metformin group at 3 and 9 months after metformin discontinuation. Interestingly, 3 months after treatment discontinuation, leptin levels showed a reduction in both metformin (baseline, 25.3 ± 14.7, week 7: 5.7 ± 3.7 ng/mL) and topiramate (baseline: 28.4 ± 16.1, week 7: 9.2 ± 15.5 ng/mL) groups. The trend of weight changes supports the superiority of metformin at 1000 mg/d over topiramate at 100 mg/d in weight reduction and weight maintenance.

A New Approach to the Prophylaxis of Cyclic Vomiting: Topiramate.

Background/AimsThe aim of this study was to compare the efficacy and tolerability of topiramate and propranolol in preventing pediatric cyclic vomiting syndrome.MethodsA retrospective medical-record review of patients who underwent prophylaxis after receiving a diagnosis of cyclic vomiting syndrome was performed. Patients who completed at least 12 months of treatment were included in the analysis. Responder rate, and adverse-event rates were also calculated from all patients. Response to treatment was assessed as the total number of vomiting attacks per year. Patients in whom the frequency of vomiting attack reduced greater or equal to 50% were defined as responders, and the remaining patients were classified as nonresponders.ResultsA total of 38 patients who were treated prophylactically with either topiramate (16 patients) or propranolol (22 patients) were identified. Fifty-nine percent of the patients in the propranolol group and 81% of the patients in the topiramate group reported freedom from attacks. A decrease of more than 50% in attacks per year occurred in 23% of patients in the propranolol group and 13% of patients in the topiramate group. The responder rates were 81% for propranolol group and 94% for topiramate group (P = 0.001). Despite minor adverse effects (drowsiness, nervousness, and dizziness) observed in a few patients, the adverse event rates were not significantly different between the 2 groups (P = 0.240).ConclusionsThe efficacy of topiramate was superior to propranolol for the prophylaxis of pediatric cyclic vomiting syndrome.

Comparative Pre-Emptive Analgesic Efficacy Study of Novel Antiepileptic Agents Lamotrigine and Topiramate in Patients Undergoing Major Surgeries at a Tertiary Care Hospital: A Randomized Double Blind Clinical Trial

Background: Central nervous sensitization, following surgical injury, leads to postoperative pain hypersensitivity due to lowered pain threshold in peripheral nociceptors and increased excitability of spinal neurons. Pre-emptive analgesia is intended to decrease pain perception and overall analgesic need by use of drug regimen, seizing CNS sensitization before exposure to painful stimuli. Few studies support pre-emptive analgesic efficacy of novel antiepileptic agent Gabapentin. Though Topiramate and Lamotrigine have been proven analgesic in animal models of chronic pain and clinical studies of Gabapentin-resistant neuropathic pain, literature search revealed scarce data on its pre-emptive analgesic efficacy. Purpose: This study is designed to study and compare the pre-emptive analgesic efficacy of Lamotrigine, Topiramate, and Diclofenac sodium in postoperative pain control. Methods: This randomized clinical trial included 90 patients of either sex, between 18 and 70 years undergoing major surgeries. Patients were randomly allocated to control and test groups and received respective treatment 30 min before induction of anesthesia. Aldrete's and pain scores were recorded using the Visual Analog Scale, Facial and Behavioral Rating Scale at awakening and at 1, 2, 4, 6, and 24 h. Postoperative rescue analgesic consumption for 24 h was recorded. Results: Significantly higher pain scores were observed in the Topiramate group postoperatively for 2 h on all pain scales (p < 0.05), whereas in the control group it was significantly higher at 1 h (p < 0.05). Lamotrigine-treated patients were more comfortable throughout the study with significantly less (p < 0.05) postoperative analgesic requirement. Conclusions: Study results strongly suggest the pre-emptive analgesic efficacy of a single oral dose of Lamotrigine over Diclofenac and Topiramate in postoperative pain control.

Efficacy for Psychopathology and Body Weight and Safety of Topiramate-Antipsychotic Cotreatment in Patients With Schizophrenia Spectrum Disorders: Results From a Meta-Analysis of Randomized Controlled Trials.

To meta-analyze the efficacy and tolerability of topiramate-antipsychotic cotreatment in schizophrenia. PubMed/MEDLINE database were searched until September 5, 2015, using the keywords topiramate AND antipsych* OR neurolept* OR specific antipsychotic names. Randomized controlled trials (RCTs) of topiramate-antipsychotic cotreatment versus placebo and ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders were included. Two evaluators extracted data. Standardized mean difference (SMD), weighted mean difference (WMD), and risk ratio (RR) ± 95% CIs were calculated. In 8 RCTs, lasting a mean ± SD of 13.6 ± 4.9 weeks, 439 patients were randomized to topiramate (100-400 mg/d) versus placebo (trials = 7) or ongoing antipsychotic treatment (trial = 1). Topiramate outperformed the comparator regarding total psychopathology (trials = 6, n = 269, SMD = -0.57 [95% CI, -1.01 to -0.14], P = .01), positive symptoms (trials = 4, n = 190, SMD = -0.56 [95% CI, -1.0 to -0.11], P = .01), negative symptoms (trials = 4, n = 190, SMD = -0.62 [95% CI, -1.13 to -0.10], P = .02) general psychopathology (trials = 3, n = 179, SMD = -0.69 [95% CI, -1.27 to -0.11], P = .02), body weight (trials = 7, n = 327, WMD = -3.14 kg [95% CI, -5.55 to -0.73], P = .01), and body mass index (BMI) (trials = 4, n = 198, WMD = -1.80 [95% CI, -2.77 to -0.84], P = .0003). Topiramate's efficacy for total psychopathology and weight reduction effects were not mediated/moderated by trial duration, topiramate dose, sex, age, inpatient status, baseline Positive and Negative Syndrome Scale, or baseline BMI. Conversely, clozapine-topiramate cotreatment moderated greater efficacy, but less weight loss, compared to topiramate-nonclozapine antipsychotic combinations. All-cause discontinuation was similar between topiramate and control groups (trials = 7, RR = 1.24 [95% CI, 0.76 to 2.02], P = .39). Topiramate trended only toward more paresthesia than placebo (trials = 4, RR = 2.03 [95 % CI, 0.99 to 4.18], P = .05). Topiramate-antipsychotic cotreatment significantly reduced total, positive, negative, and general psychopathology and weight/BMI in patients with schizophrenia spectrum disorder while being well tolerated. However, larger studies are needed to confirm and extend these findings.

Efficacy of topiramate in the treatment of crack cocaine dependence: a double-blind, randomized, placebo-controlled trial.

We performed a double-blind, randomized, placebo-controlled trial to assess the efficacy of topiramate in the treatment of crack cocaine dependence. Sixty men who were dependent on cocaine (DSM-IV) (exclusive use of crack cocaine) were selected. The subjects were randomly assigned to either a topiramate group (subjects received 50-200 mg of topiramate per day for 12 weeks) or a control group (subjects received placebo). The initial daily treatment dose was 50 mg, and this dose was increased weekly at increments of 25 to 50 mg, based on the subject's tolerability, to a maximum of 200 mg. All of the subjects also participated in motivational interviews and group therapy. The primary outcome measures were detection of benzoylecgonine in the urine, study retention, frequency of cocaine smoking, amount of cocaine use, and mean amount of money spent on cocaine per week. The study was conducted from February 2013 to February 2014. Twenty-nine subjects in the topiramate group and 29 subjects in the control group completed the study. Longitudinal assessment revealed that retention was not significant (odds ratio [OR] = 1.072, P = .908) between the 2 groups. Negative results from a urine test for benzoylecgonine (a cocaine metabolite), which is a measure of cocaine abstinence, were more frequently obtained from the topiramate group (OR = 8.687, P < .001). Topiramate reduced the quantity of cocaine used (mean reduction = -3.108 g, P < .001), the frequency of cocaine use (mean = -0.784 times per week, P = .005), and the amount of money spent on cocaine (mean [US dollars] = -$25.38, P = .015; this variable did not achieve statistical significance after Bonferroni correction) compared with the placebo during the 12 weeks (or 84 days) of the assessment. However, the differences in reductions between the 2 groups in the quantity of cocaine used, the frequency of cocaine use, and money spent on cocaine over time (time × group interaction) were present only during the first 4 weeks, and none of these variables by 12 weeks. The studied groups did not differ with regard to secondary end points, such as study dropout and the number of subjects who reported side effects. The present findings indicate that topiramate is effective and safe and thus reinforce previous data suggesting that topiramate is a potentially useful treatment for crack cocaine dependence. However, we found that topiramate is only useful as an adjunctive treatment during the first 4 weeks of the treatment. Future studies with larger samples are needed to confirm these results. Registro Brasileiro de Ensaios Clínicos (ReBEC) RBR-3vwfjs and UTN: U1111-1131-4443.

Topiramate for the management of methamphetamine dependence: a pilot randomized, double-blind, placebo-controlled trial.

To date, no medication has been approved as an effective treatment for methamphetamine dependence. Topiramate has attracted considerable attention as a treatment for the dependence on alcohol and stimulants. Therefore, this study aimed to evaluate the effect of topiramate for methamphetamine dependence. This study was a double-blind, randomized, placebo-controlled trial. In the present investigation, 62 methamphetamine-dependent adults were enrolled and randomized into two groups, and received topiramate or a placebo for 10 weeks in escalating doses from 50 mg/day to the target maintenance dose of 200 mg/day. Addiction severity index (ASI) and craving scores were registered every week. The Beck questionnaire was also given to each participant at baseline and every 2 weeks during the treatment. Urine samples were collected at baseline and every 2 weeks during the treatment. Fifty-seven patients completed 10 weeks of the trial. There was no significant difference between both groups in the mean percentage of prescribed capsules taken by the participants. At week six, the topiramate group showed a significantly lower proportion of methamphetamine-positive urine tests in comparison with the placebo group (P = 0.01). In addition, there were significantly lower scores in the topiramate group in comparison with the placebo group in two domains of ASI: drug use severity (P < 0.001) and drug need (P < 0.001). Furthermore, the craving score (duration) significantly declined in the topiramate patients compared to those receiving the placebo. In conclusion, the results of this trial suggest that topiramate may be beneficial for the treatment of methamphetamine dependence.

A randomized, placebo-controlled proof-of-concept trial of adjunctive topiramate for alcohol use disorders in bipolar disorder.

Topiramate is effective for alcohol use disorders (AUDs) among non-psychiatric patients. We examined topiramate for treating comorbid AUDs in bipolar disorder (BD). Twelve participants were randomized to topiramate or placebo for 12 weeks. The topiramate group, with two out of five participants (40%) completing treatment, experienced less improvement in drinking patterns than the placebo group, with five out of seven participants (71%) completing treatment. Topiramate did not improve drinking behavior and was not well-tolerated. This study failed to recruit adequately. Problems surrounding high attrition, a small study sample, and missing data preclude interpretation of study findings. This is the first randomized, placebo-controlled trial of topiramate for AUDs in BD.

Effects of Topiramate for atypical antipsychotic-induced body weight gain and metabolic adversities: a systematic review and meta-analysis

To systematically determine the effectiveness of Topiramate to counteract atypical antipsychotic-induced body weight gain and metabolic adversities in patients with psychiatric disorders. A literature search using MEDLINE, EMBASE, PsycINFO, The Cochrane Library, CNKI, CBM and WanFang Data for randomized, open and double-blind, placebo-controlled trials of Topiramate targeting atypical antipsychotic-induced weight gain was performed.Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies.Then meta-analysis was performed using RevMan 5.2 software. A total of 10 RCTs was included, consisting of 453 subjects. The results of meta-analysis showed that: compared with placebo, Topiramate was moderate effective in reducing antipsychotics-related weight gain (WMD=-1.82 kg (95%CI: -2.65--0.99), P<0.000 1), BMI increase (WMD=-1.31 kg/m(2) (95%CI: -1.69--0.93), P<0.000 01) and fasting glucose increase (SMD=-1.15 (95%CI: -1.50--0.79), P<0.000 01); but can not regulate the lipid metabolic disorders (Cholesterol: SMD=-0.23 (95%CI: -0.81-0.35), P=0.44); Triglycerides: SMD=-0.28 (95%CI: -0.75-0.19), P=0.24; HDL: SMD= 0.01 (95%CI: -0.52-0.53), P=0.98); LDL: SMD=-0.39 (95%CI: -0.89-0.11), P=0.13). Meanwhile, when compared with placebo, Positive and Negative Syndrome Scale (PANSS) in patients with schizophrenia did not show obviously clinical improvement in concomitant Topiramate group. Topiramate can prevent and/or treat atypical antipsychotic induced weight gain and glucose disorder, but current evidence does not support the effect of Topiramate in lipid metabolic regulation and the clinical symptoms improvement assessed by PANSS.

Topiramate and motivational enhancement therapy for cannabis use among youth: a randomized placebo-controlled pilot study.

Cannabis misuse accounts for nearly all of the substance abuse treatment admissions among youth in the United States. Most youth do not experience sustained benefit from existing psychosocial treatments; however, medication development research for treating adolescent cannabis misuse is almost nonexistent. We conducted a double-blind, placebo-controlled, pilot study to test the potential efficacy of topiramate plus motivational enhancement therapy (MET) for treating cannabis use among adolescents. Sixty-six heavy cannabis users, ages 15 to 24 years, were randomized to one of two 6-week treatment conditions: topiramate plus MET or placebo plus MET. Topiramate was titrated over 4 weeks then stabilized at 200 mg/day for 2 weeks. MET was delivered biweekly for a total of three sessions. Only 48 percent of youths randomized to topiramate completed the 6-week trial (n = 19), compared with 77 percent of youths in the placebo condition (n = 20). Adverse medication side effects were the most common reason for withdrawal among participants in the topiramate group. Latent growth models showed that topiramate was superior to placebo for reducing the number of grams smoked per use day, but it did not improve abstinence rates. The same pattern of results was found when values for missing outcomes were imputed. We show that topiramate combined with MET demonstrated efficacy for reducing how much cannabis adolescents smoked when they used but did not affect abstinence rates. The magnitude of this effect was modest, however, and topiramate was poorly tolerated by youths, which calls into question the clinical importance of these findings.

Topiramate as Migraine Prophylaxis in Pediatric Patients: An Integrated Summary of Randomized Controlled Trials

Background: An integrated analysis of five randomized, placebo-controlled studies in migraine prophylaxis was conducted to assess topiramate’s efficacy and safety in pediatric patients. Methods: Study 1, a pivotal study (50-, 100 mg/day; aged 12-17 years), Study 2 (flexibly-dosed 2-3 mg/kg/day; aged 6-15 years), and Studies 3, 4 and 5 [50-, 100-, 200 mg/day; aged ≥ 12 years)]. Results: Percent reduction in the average monthly migraine attack rate: Study 1: the 100 mg/day group improved versus placebo (72% versus 44%, p=0.0164); Study 2: topiramate was not significantly different from placebo (58% versus 48%); Studies 3, 4 and 5: positive trend in the 100 mg/day group versus placebo (75% versus 37%). ≥ 50% reduction responder rate: Study 1 - the 100 mg/day group improved versus placebo (83% versus 45%, [p=0.0048]); no significant effect for topiramate versus placebo was seen in either Study 2 (56% versus 49%), or Studies 3, 4 and 5 (69% versus 33%). Most common treatment-emergent adverse events in topiramate group were influenza-like symptoms, language problems and paresthesia. Conclusion: Overall, topiramate was efficacious for migraine prophylaxis in adolescent patients (12-17 years). The most consistent results were observed with topiramate 100 mg/day dose, which was generally well-tolerated.