topiramate and Substance-Related-Disorders

Topiramate has been approved by the US Food and Drug Administration for the treatment of epilepsy since the 1990s, and it has also been used off-label in the treatment of many types of addictive disorders. To date, no systematic review has embraced the entire field of addiction, both substance use and behavioral addictions, including eating disorders, to compare topiramate-based protocols and the related level of evidence in each addictive disorder. Our objective is to fill this gap.. A systematic search was conducted using the MEDLINE, PsycINFO, and Cochrane databases without a date or language limit. All trials and meta-analyses assessing the efficacy of topiramate in alcohol use disorder; cocaine use disorder; methamphetamine, nicotine, cannabis, opiate, and benzodiazepine use disorders; binge eating disorder; bulimia; and pathological gambling were analyzed. The quality of the studies was rated using the Cochrane Risk-of-Bias tool for randomized trials (ROB-2), the Risk of Bias In Nonrandomized Studies (ROBINS-I), or the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, depending on the study design. Safety features were assessed based on a wider non-systematic review.. Sixty-two articles were reviewed. Treatment protocols were relatively homogenous across addictive disorders, with slow dose titration schemes and a maximum dose range of 200-400 mg per day. The most supportive evidence for topiramate efficacy was found in alcohol use disorder for drinking reduction parameters only. To a lesser extent, topiramate could be a promising therapeutic option for binge eating disorder and cocaine use disorder. Evidence was weak for other addictive disorders. No major tolerability issues were found, provided that basic safety rules were followed. Adverse drug reactions could lead to early treatment discontinuation.. Though off-label, addiction specialists should consider topiramate as a second-line option for drinking reduction in alcohol use disorder, as well as for binge eating disorder or cocaine use disorder.

Topics: Alcohol Drinking; Alcoholism; Anticonvulsants; Behavior, Addictive; Dose-Response Relationship, Drug; Feeding and Eating Disorders; Humans; Off-Label Use; Randomized Controlled Trials as Topic; Substance-Related Disorders; Topiramate

Substance use disorders (SUDs), including those for alcohol, stimulants, tobacco, opioids and cannabis, in patients with bipolar disorder are a major clinical and public health problem, and are present in the majority of these patients. Nonetheless, the development of effective pharmacological treatments for co-occurring SUDs in bipolar illness have not been well-developed and may be an important practical reason for the reduced effectiveness of these medications in community practice.. We conducted a systematic review of the literature (PubMed, Medline, Google Scholar), and identified N = 29 clinical studies, which evaluated both mental health and SUD outcomes in patients with co-occurring bipolar disorders and SUDs.. Our findings suggest the potential of valproate sodium and lamotrigine as preferred pharmacological agents for the treatment of co-occurring psychiatric and substance use outcomes in these patients. However, many of the reviewed studies are of open-label designs and of modest sample sizes.. Thus, given the gaps in our knowledge, recommendations for treatment of this common and important co-morbidity are preliminary. Accordingly, the conduct of larger, randomized controlled trials for this co-morbidity is clearly needed.

Topics: Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Comorbidity; Humans; Lamotrigine; Lithium Compounds; Quetiapine Fumarate; Substance-Related Disorders; Topiramate; Valproic Acid

Drug treatments used in substance use disorders are not effective in all patients.. To assess the effectiveness of topiramate use in the treatment of substance use disorders.. Medline database from January 1966 to December 2013, Cochrane database and clinicaltrials.gov.. We used keywords topiramate, addiction, substance abuse, alcohol, tobacco, nicotine, cocaine, methamphetamine, opiate, heroin, benzodiazepine, cannabis, bulimia nervosa, binge eating disorder, gambling. All clinical trials were included. Animal trials, laboratory tests, reviews, answers to writers, case-reports, case series and publications unrelated to the topic were excluded. Twenty-eight articles investigating the efficacy of topiramate in substance use were included.. In alcohol-related disorder, several trials and a meta-analysis showed a reduction of days of consumption. In a single-center trial on tobacco-related disorder, topiramate was not found effective in reducing the carbon monoxide expired. In cocaine-related disorder, one single-center trial showed a reduction of days of consumption and two single-center trials have found a trend in favour of topiramate. In alcohol and cocaine co-dependency, a single-center trial found a trend in favour of topiramate. In methamphetamine-related disorder, a multicenter trial found a trend in favour of topiramate. In bulimia nervosa, two single-center trials showed a reduction in binge eating and compensatory behaviours. In binge eating disorder, several trials showed a reduction of binge eating and weight. In gambling, one single-center trial did not show any significant results. There were no randomized controlled trials found in opioid-related disorder, benzodiazepines-related disorder, and cannabis-related disorder.. Definition of abstinence and methods to assess the efficacy of topiramate differed between trials. The methodological quality of included trials was variable, especially with no double-blind procedure in eight trials.. Topiramate showed interest mainly in alcoholism, binge eating disorder and bulimia nervosa. No definitive conclusions can be reached for other substance use disorders such as nicotine dependence, cocaine dependence, amphetamine dependence or cannabis dependence and for gambling.

Topics: Behavior, Addictive; Clinical Trials as Topic; Feeding and Eating Disorders; Fructose; Gambling; Humans; Neuroprotective Agents; Substance-Related Disorders; Topiramate

To critically review the literature on topiramate in the treatment of substance-related disorders.. A PubMed search of human studies published in English through January 2009 was conducted using the following search terms: topiramate and substance abuse, topiramate and substance dependence, topiramate and withdrawal, topiramate and alcohol, topiramate and nicotine, topiramate and cocaine, topiramate and opiates, and topiramate and benzodiazepines.. 26 articles were identified and reviewed; these studies examined topiramate in disorders related to alcohol, nicotine, cocaine, methamphetamine, opioids, Ecstasy, and benzodiazepines.. Study design, sample size, topiramate dose and duration, and study outcomes were reviewed.. There is compelling evidence for the efficacy of topiramate in the treatment of alcohol dependence. Two trials show trends for topiramate's superiority over oral naltrexone in alcohol dependence, while 1 trial suggests topiramate is inferior to disulfiram. Despite suggestive animal models, evidence for topiramate in treating alcohol withdrawal in humans is slim. Studies of topiramate in nicotine dependence show mixed results. Human laboratory studies that used acute topiramate dosing show that topiramate actually enhances the pleasurable effects of both nicotine and methamphetamine. Evidence for topiramate in the treatment of cocaine dependence is promising, but limited by small sample size. The data on opioids, benzodiazepines, and Ecstasy are sparse.. Topiramate is efficacious for the treatment of alcohol dependence, but side effects may limit widespread use. While topiramate's unique pharmacodynamic profile offers a promising theoretical rationale for use across multiple substance-related disorders, heterogeneity both across and within these disorders limits topiramate's broad applicability in treating substance-related disorders. Recommendations for future research include exploration of genetic variants for more targeted pharmacotherapies.

Topics: Alcohol-Related Disorders; Amphetamine-Related Disorders; Cocaine-Related Disorders; Fructose; Humans; Neuroprotective Agents; Opioid-Related Disorders; Substance-Related Disorders; Tobacco Use Disorder; Topiramate

These practice guidelines for the biological treatment of substance use disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal during the development of these guidelines was to review systematically all available evidence pertaining to the treatment of substance use disorders, and to reach a consensus on a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by physicians evaluating and treating people with substance use disorders and are primarily concerned with the biological treatment of adults suffering from substance use disorders. The data used to develop these guidelines were extracted primarily from various national treatment guidelines for substance use disorders, as well as from meta-analyses, reviews and randomized clinical trials on the efficacy of pharmacological and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorized into four levels of evidence (A-D). This first part of the guidelines covers the treatment of alcohol dependence; Part 2 will be devoted to the treatment of drug dependence.

Topics: Acamprosate; Alcohol Deterrents; Alcohol-Related Disorders; Biological Psychiatry; Carbamazepine; Disulfiram; Fructose; Health Planning Guidelines; Humans; Naltrexone; Ondansetron; Societies, Scientific; Substance-Related Disorders; Taurine; Topiramate

Topiramate is an anticonvulsant currently under study for treating substance use disorders. Topiramate is thought to reduce substance use by attenuating craving and the rewarding effects of acute substance use through its concurrent GABAergic agonism and glutamatergic antagonism. Importantly, topiramate also impacts mood states central to many models of substance use. Despite this, little previous research has examined whether topiramate attenuates the respective associations of affect and craving with substance use.. We conducted a secondary analysis of 63 youths that exhibited heavy cannabis use, aged 15-24 years, who were randomized in a double-blinded 6-week clinical trial comparing the effects of topiramate (up to 200 mg/day) and placebo on cannabis use. Ecological momentary assessment data were leveraged to model the role positive affect, negative affect, and craving on use over the 6-week period and whether topiramate attenuated associations between these feeling states and cannabis use.. Findings showed that craving was positively associated with use at the within-person level, while positive affect was negatively associated with use at the between-person level. Topiramate appears to attenuate the negative association of between-person positive affect (i.e., average) and cannabis use. Specifically, those in the placebo condition exhibited this inverse association between average positive affect and use while those in topiramate condition did not. No other significant affect or affect × medication condition interactions were observed.. These findings implicate craving and low positive affect as important risk factors for cannabis use in youth in treatment. Topiramate may attenuate this association for positive affect.

Topics: Adolescent; Affect; Cannabis; Craving; Ecological Momentary Assessment; Humans; Substance-Related Disorders; Topiramate

Cocaine use contines to be a significant public health problem world-wide. However, despite substantial research efforts, no pharmacotherapies are approved for the treatment of cocaine use disorder (CUD).. Studies have identified positive signals for a range of medications for treating CUD. These include long-acting amphetamine formulations, modafinil, topiramate, doxazosin and combined topiramate and mixed amphetamine salts extended-release (MAS-ER). However, valid conclusions about a medication's clinical efficacy require nuanced approaches that take into account behavioural phenotypes of the target population (frequency of use, co-abuse of cocaine and other substances, genetic subgroups, psychiatric comorbidity), variables related to the medication (dose, short-/long-acting formulations, titration speed, medication adherence) and other factors that may affect treatment outcomes. Meta-analyses frequently do not account for these co-varying factors, which contributes to a somewhat nihilistic view on pharmacotherapeutic options for CUD. In addition, the predominant focus on abstinence, which is difficult for most patients to achieve, may overshadow more nuanced therapeutic signals.. While there is an emphasis on finding new medications with novel mechanisms of action for treating CUD, currently available medications deserve further investigation based on the existing literature. Evaluating refined metrics of treatment success in well-defined subgroups of patients, and further exploring combination therapies and their synergy with behavioural/psychosocial interventions, are promising avenues to establishing effective therapies for CUD.

Topics: Amphetamine; Cocaine; Cocaine-Related Disorders; Humans; Substance-Related Disorders; Topiramate

Topics: Accreditation; Adrenergic alpha-2 Receptor Agonists; Anticonvulsants; Antiemetics; Baclofen; Clonidine; Excitatory Amino Acid Antagonists; GABA Agents; Gabapentin; Health Facility Size; Humans; Logistic Models; Off-Label Use; Ondansetron; Practice Patterns, Physicians'; Substance Abuse Treatment Centers; Substance-Related Disorders; Time Factors; Topiramate; United States; Valproic Acid

Abuses of methylphenidate (MPH) as psychostimulant cause neural damage of brain cells. Neuroprotective properties of topiramate (TPM) have been indicated in several studies but its exact mechanism of action remains unclear. The current study evaluates protective role of various doses of TPM and its mechanism of action in MPH induced oxidative stress and inflammation. The neuroprotective effects of various doses of TPM against MPH induced oxidative stress and inflammation were evaluated and then the action of TPM was studied in presence of domoic acid (DOM), as AMPA/kainate receptor agonist and bicuculline (BIC) as GABAA receptor antagonist, in isolated rat hippocampus. Open Field Test (OFT) was used to investigate motor activity changes. Oxidative, antioxidant and inflammatory factors were measured in isolated hippocampus. TPM (70 and 100mg/kg) decreased MPH induced motor activity disturbances and inhibit MPH induced oxidative stress and inflammation. On the other hand pretreatment of animals with DOM or BIC, inhibit this effect of TPM and potentiate MPH induced motor activity disturbances and increased lipid peroxidation, mitochondrial oxidized form of glutathione (GSSG) level, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in isolated hippocampal cells and decreased reduced form of glutathione (GSH) level, superoxide dismutase, glutathione peroxidase and glutathione reductase activity. It seems that TPM can protect cells of hippocampus from oxidative stress and neuroinflammation and it could be partly by activation of GABAA receptor and inhibition of AMPA/kainite receptor.

Topics: Animals; Behavior, Animal; Dose-Response Relationship, Drug; Female; Fructose; Glutathione Disulfide; Hippocampus; Inflammation; Ligand-Gated Ion Channels; Lipid Peroxidation; Male; Methylphenidate; Mitochondria; Neuroprotective Agents; Oxidative Stress; Oxidoreductases; Rats; Receptors, AMPA; Receptors, GABA-A; Receptors, Kainic Acid; Substance-Related Disorders; Superoxide Dismutase; Topiramate

Patients with chronic migraine (CM) and medication abuse are difficult to treat, and have a greater tendency towards chronification and a poorer quality of life than those with other types of headache.. To evaluate whether the presence of medication abuse lowers the effectiveness of topiramate.. A series of patients with CM were grouped according to whether they met abuse criteria or not. They were advised to stop taking the drug that they were abusing. Treatment was adjusted to match their crises and preventive treatment with topiramate was established from the beginning. The number of days with headache and intense migraine in the previous month and at four months of treatment was evaluated.. In all, 262 patients with CM criteria were selected and 167 (63.7%) of them fulfilled abuse criteria. In both groups there was a significant reduction in the number of days with headache/month and number of migraine attacks/month at the fourth month of treatment with topiramate. The percentage of reduction in the number of days with headache/month in CM without abuse was 59.3 ± 36.1%, and with abuse, 48.7 ± 41.7% (p = 0.0574). The percentage of reduction in the number of days with intense migraine/month in CM without abuse was 61.2%, and with abuse, 50% (p = 0.0224). Response rate according to the number of days with headache/month in CM without abuse was 69%, and with abuse, 57%. Response rate according to the number of intense migraines/month in CM without abuse was 76.8%, and in CM with abuse, 61% (p = 0.0097).. Topiramate was effective in patients with CM with and without medication abuse, although effectiveness is lower in the latter case.. El abuso de farmacos en pacientes con migraña cronica influye en la efectividad del tratamiento preventivo con topiramato?. Introduccion. Los pacientes con migraña cronica (MC) y abuso de medicacion son dificiles de tratar y tienen peor calidad de vida que otros pacientes con migrañas. Objetivo. Valorar si la presencia de abuso de farmacos disminuye la efectividad del topiramato. Pacientes y metodos. Una serie de pacientes con MC fueron agrupados segun presentasen criterios de abuso o no abuso de farmacos. Se les aconsejo la supresion del farmaco del cual abusaban. Se ajusto el tratamiento de sus crisis y se inicio tratamiento preventivo desde el principio con topiramato. Se valoro el numero dias con cefalea y migrañas intensas en el mes previo y al cuarto mes de tratamiento. Resultados. Fueron seleccionados 262 pacientes con criterios de MC, y de ellos 167 (63,7%) cumplieron criterios de abuso. En ambos grupos hubo una reduccion significativa del numero de dias con cefalea/mes y numero de crisis de migraña/mes al cuarto mes de tratamiento con topiramato. Porcentaje de reduccion de dias con cefalea/mes en MC sin abuso, 59,3 ± 36,1%; y con abuso, 48,7 ± 41,7% (p = 0,0574). Porcentaje de reduccion de migrañas intensas/mes en MC sin abuso, 61,2%; y con abuso, 50% (p = 0,0224). Tasa de respondedores segun numero de dias con cefalea/mes en MC sin abuso, 69%; y con abuso, 57%. Tasa de respondedores segun numero de migrañas intensas/mes en MC sin abuso, 76,8%; y en MC con abuso, 61% (p = 0,0097). Conclusiones. El topiramato fue efectivo en pacientes con MC sin y con abuso de farmacos, aunque con menor efectividad en estos ultimos.

Topics: Adult; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Drug Interactions; Drug Overdose; Female; Fructose; Headache Disorders; Headache Disorders, Secondary; Humans; Male; Middle Aged; Migraine Disorders; Patient Satisfaction; Substance-Related Disorders; Topiramate; Treatment Outcome; Tryptamines; Young Adult

Topics: Anti-Obesity Agents; Appetite Depressants; Fructose; Humans; Obesity; Phentermine; Substance-Related Disorders; Topiramate

A 34-year-old woman presented with new intermittent short lasing headache around the left eye accompanied with lacrimation. She suffered from anemia and visual disturbance due to thalassaemia beta heterotype and retinitis pigmentosa. She also had continual cephalalgia from about 9 years old, and was taking nonsteroidal anti-inflammatory drug almost every day. After the medical treatment, we diagnosed her headache as migraine without aura, medication overuse headache (MOH) and short lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). Triptan was effective for a migraine headache, but it was ineffective for attacks of SUNA, while topiramate dramatically reduced the SUNA attacks. A headache diary was effective to evaluate the clinical course and the effect of treatment for two different types of headaches by devising the approach to description. A migraine and MOH may coexist with SUNA, and our attention should be paid to the diagnosis and medical treatment in such cases.

Topics: Adult; Female; Fructose; Headache; Humans; Migraine Disorders; Substance-Related Disorders; Topiramate

Topiramate is one of the currently most promising compounds in the field of addiction medicine. This paper discusses its potential utility related to a phase model of addiction development, focusing on the assumption that addiction is a continuous process involving different neurobiological pathways, depending on the stage of addiction. A specific emphasis will be made on the development of dysfunctional automatic behaviors in late stage of addiction and the central role of glutamate and AMPA receptors. The aim is to propose that if a too broad effect of anti-addiction medication is expected (such as anti-craving, anti-relapse and preventive effects), the results might be disappointing. The speculative specific efficacy of topiramate in addiction is described.

Topics: Behavior, Addictive; Drug Delivery Systems; Fructose; Glutamic Acid; Humans; Models, Biological; Neuroprotective Agents; Receptors, AMPA; Secondary Prevention; Substance-Related Disorders; Topiramate

Topics: Alcoholism; Anticonvulsants; Benzodiazepines; Central Nervous System Agents; Female; Fructose; Humans; Lamotrigine; Middle Aged; Secondary Prevention; Substance-Related Disorders; Time Factors; Topiramate; Treatment Outcome; Triazines

Anticonvulsant drugs have demonstrated efficacy in the management of irritability and aggression in a variety of psychiatric populations. We examined the acute effects of topiramate on aggression using a laboratory model of human aggression (PSAP) in individuals at high risk for aggressive and violent behavior.Twelve subjects, on parole/probation and with an Axis-II personality disorder and/or a substance use disorder, received 100, 200, 300, and 400 mg in an ascending sequence, with intervening placebo doses.Subjects participated 2-3 days per week over 4-6 weeks. Due to cognitive side effects at 300 mg, two subjects only completed through the 200 mg dose. Topiramate produced an inverted U-shaped dose response curve, with increases in aggression peaking at 200 mg and a modest decrease at 400 mg. Statistical analysis revealed a polynomial trend for dose (p=0.001). The observed inverted U-shaped function in aggressive responding is consistent with non-human aggression studies of GABA-A modulators. Acute topiramate doses >400 mg may have anti-aggressive effects, but dose levels in the 200-300 mg range may produce increases in aggression and side effects.

Topics: Adult; Aggression; Dose-Response Relationship, Drug; Female; Fructose; Humans; Male; Social Behavior; Substance-Related Disorders; Topiramate

In recent years topiramate has been used for psychiatric patients, mainly for controlling substance use and food intake. A total of 46 patients who received topiramate treatment during the study period were identified from a computer database. Nineteen had received topiramate for at least 1 month. Twelve patients received topiramate for anticraving effects (alcohol, n = 9; heroin/amphetamine, n = 1; meperidine, n = 1; and nicotine, n = 1). On an average dosage of 112.5 mg/day, nine of the 12 patients (excluding three alcoholic patients) achieved complete or partial remission from the substance use disorders. The present results show that six of the nine patients achieved full or partial remission from alcohol use disorder on a dosage of 100 mg/day. Topiramate was also used to control seven patients' bodyweight (mean bodyweight change, 1.53 kg). Four of them achieved bodyweight loss in the 1-month follow up, with an average change of 2.65 kg. Based on the present findings topiramate <100 mg/day may be effective in treating patient with alcohol use disorder, and that topiramate has not shown remarkable benefit of bodyweight loss.

Topics: Adult; Agoraphobia; Anti-Obesity Agents; Body Weight; Databases, Factual; Depressive Disorder, Major; Eating; Female; Fructose; GABA Antagonists; Humans; Male; Middle Aged; Retrospective Studies; Substance-Related Disorders; Topiramate; Treatment Outcome

Alprazolam is successful in reducing anxiety but has a high addictive/misuse potential. Topiramate is a novel anticonvulsant which has been used as a mood stabilizer. Other anticonvulsants, such as carbamazepine and valproate, have been used in alcohol and benzodiazepine withdrawal. Topiramate has recently been used in alcohol, cocaine and opiates withdrawal. There has been also one report of topiramate use in midazolam withdrawal. In our case of a patient with recurrent major depressive disorder, subthreshold anxiety disorder and addiction to alprazolam, topiramate appears to be efficient and safe in alprazolam withdrawal.

Topics: Adult; Alprazolam; Anti-Anxiety Agents; Anticonvulsants; Antidepressive Agents, Second-Generation; Anxiety Disorders; Cyclohexanols; Depressive Disorder, Major; Female; Fructose; Humans; Substance Withdrawal Syndrome; Substance-Related Disorders; Topiramate; Treatment Outcome; Venlafaxine Hydrochloride

Topics: Adult; Bipolar Disorder; Borderline Personality Disorder; Comorbidity; Drug Overdose; Feeding and Eating Disorders; Female; Fructose; Humans; Substance-Related Disorders; Topiramate; Weight Gain