topiramate and Opioid-Related-Disorders

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

Topiramate is being investigated as a potential pharmacotherapy for the treatment of addictive disorders. However, its cognitive side effects raise concerns about its use, especially in populations with cognitive impairment, such as persons with chronic substance use disorders. This study investigated topiramate's cognitive effects in individuals dually dependent on cocaine and opioids as part of a double-blind, randomized, controlled trial of topiramate for cocaine dependence treatment. After 5 weeks of stabilization on daily oral methadone (M = 96 mg), participants were randomized to topiramate (n = 18) or placebo (n = 22). Cognitive testing took place at 2 time points: study weeks 4 through 5 to assess baseline performance and 10 to 13 weeks later to assess performance during stable dosing (300 mg topiramate or placebo). All participants were maintained on methadone at both testing times, and testing occurred 2 hours after the daily methadone plus topiramate/placebo administration. The topiramate and placebo groups did not differ on sex, level of education, premorbid intelligence, methadone dose, or illicit drug use. Topiramate slowed psychomotor and information processing speed, worsened divided attention, reduced n-back working memory accuracy, and increased the false alarm rate in recognition memory. Topiramate had no effects on visual processing, other measures of psychomotor function, risk-taking, self-control, Sternberg working memory, free recall, and metamemory. These findings indicate that topiramate may cause cognitive impairment in this population. This effect may limit its acceptability and use as a treatment in individuals with chronic opioid and cocaine use disorders, among whom preexisting cognitive impairments are common. (PsycINFO Database Record

Topics: Adult; Cocaine-Related Disorders; Cognition Disorders; Diagnosis, Dual (Psychiatry); Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Methadone; Neuropsychological Tests; Opiate Substitution Treatment; Opioid-Related Disorders; Topiramate

The aims of this study were to evaluate a combination of aripiprazole and topiramate in the treatment of opioid-dependent patients with schizoaffective disorder undergoing methadone maintenance therapy (MMT) and, further, to taper off patients from methadone treatment.. Twenty patients who met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for opioid dependence and schizoaffective disorder receiving MMT (80 mg/day) were given aripiprazole (10 mg/day) plus topiramate (up to 200 mg/day) for 8 weeks. A methadone dose reduction of 3 mg/day until suspension at week 4 was established.. Aripiprazole plus topiramate was effective in reducing clinical symptoms, and a rapid tapering off of MMT was achieved.. Combining aripiprazole and topiramate may be effective in patients with a dual diagnosis of opioid dependency and schizoaffective disorder.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Diagnosis, Dual (Psychiatry); Drug Administration Schedule; Drug Therapy, Combination; Female; Fructose; Humans; Male; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quinolones; Topiramate; Treatment Outcome; Young Adult

Topics: Adult; Anticonvulsants; Depressive Disorder, Major; Dextromethorphan; Excitatory Amino Acid Antagonists; Fructose; Humans; Male; Opioid-Related Disorders; Stress Disorders, Post-Traumatic; Topiramate

There are some rationales for developing anticonvulsants for the treatment of substance abuse. The blockade of the AMPA/kainate subtype of glutamate receptor by topiramate may be of particular interest, as preclinical studies of withdrawal from opioids suggest that whilst AMPA-receptor antagonists may not be able to prevent tolerance or dependence from developing, they may ameliorate both physical and emotional consequences of withdrawal.. Ten consecutively admitted patients treated with topiramate were compared in a retrospective naturalistic drug utilization observation study with 10 consecutively admitted patients treated with clonidine and with 10 consecutively admitted patients treated with a carbamazepine/ mianserin combination.. In 9 cases of the clonidine group and in 7 carbamazepine/mianserin treated patients the dose had been reduced, whereas this occurred in only 2 topiramate treated patients (p < 0.01). Patients in the topiramate group received less p.r.n. myorelaxant medication than the two other groups, and there was a significant difference between the three groups with regard to p.r.n. analgesics (p < 0.05), topiramate and clonidine treated patients receiving fewer analgesics than the carbamazepine/mianserin group.. Compared to clonidine and carbamazepine/mianserin, a detoxification scheme using high initial and then decreasing doses of topiramate appeared to be appropriate for most patients and as associated with less analgesic and myorelaxant comedication, indicating a more promising efficacy at the used doses.

Topics: Adrenergic alpha-Agonists; Adult; Anticonvulsants; Antidepressive Agents, Second-Generation; Carbamazepine; Clonidine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fructose; Humans; Male; Mianserin; Opioid-Related Disorders; Retrospective Studies; Substance Withdrawal Syndrome; Topiramate

The alpha2-adrenergic agonist clonidine is the mainly used drug for the opiate withdrawal. Its efficacy and tolerance in treating withdrawal symptoms is, however, suboptimal. The pharmacological profile of topiramate suggests it could be rather valuable for opiate withdrawal, as there is some evidence that topiramate acts, among others, through inhibition of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, which play an important role in the withdrawal-induced activation of the locus coeruleus (LC) by glutamate. Three patients undergoing an inpatient opiate detoxification program were treated with topiramate, which achieved a nearly complete control of withdrawal symptoms.

Topics: Adrenergic alpha-Agonists; Adult; Anticonvulsants; Clonidine; Female; Fructose; Heroin Dependence; Humans; Liver Function Tests; Male; Opioid-Related Disorders; Seizures; Substance Withdrawal Syndrome; Topiramate