topiramate and Substance-Withdrawal-Syndrome

Topiramate (TPM) has the potential to become one of the most prominent treatment options for alcohol use disorder (AUD). We investigated the efficacy of TPM for AUD treatment, considering new randomized controlled trials carried out since the publication of four prior investigations.. We searched six major databases, comparing TPM to placebo for AUD treatment. We performed a Bayesian meta-analysis. We conducted a meta-regression, analyzing the effect of age, TPM dosage, duration of treatment, gender, and attrition rate on the outcomes measured. The protocol is registered with PROSPERO: CRD42021286266.. TPM reduced heavy drinking days (. TPM has the potential to become a key pharmacological agent in the treatment of AUD.

Topics: Alcohol Drinking; Alcoholism; Bayes Theorem; Humans; Substance Withdrawal Syndrome; Topiramate

Extending from the triple wave epidemic of opioid-related overdose deaths, a fourth wave of high mortality involving methamphetamine and cocaine use has been gathering force. This article provides a review of the published literature on stimulants including epidemiology, pharmacology, neurobiology, medical and psychiatric consequences, withdrawal management, and medical and behavioral treatments.

Topics: Adrenergic alpha-2 Receptor Antagonists; Adult; Anticonvulsants; Behavior Therapy; Bupropion; Central Nervous System Stimulants; Cocaine-Related Disorders; Cognitive Dysfunction; Comorbidity; Dopamine Uptake Inhibitors; Female; Humans; Illicit Drugs; Male; Mental Disorders; Methamphetamine; Mirtazapine; Neurobiology; Neurodegenerative Diseases; Opiate Overdose; Substance Withdrawal Syndrome; Topiramate; Transgender Persons; United States

To date, a limited number of pharmacological agents exist to treat alcohol use disorders (AUDs), and there is growing interest in new therapeutic tools. In this framework, topiramate may represent a useful treatment option, although its use is not yet approved for AUDs. The main focus of this review is to discuss all the existing data supporting the use of topiramate in AUDs, with an emphasis on the most recent and relevant clinical implications. In addition, the profile of the alcoholic patient who may benefit more from the use of topiramate is outlined. In this regard, the authors conducted a PubMed search of clinical human studies published in English using the following key words: topiramate alcohol dependence, topiramate alcohol withdrawal and topiramate alcoholism. The evidence suggests that topiramate could be an effective treatment option for the management of AUDs, while there are limited results for its use to treat alcohol withdrawal syndrome. In particular, topiramate shows a greater beneficial effect in subjects with a typology of craving characterised by drinking obsessions and automaticity of drinking. Topiramate, within the dosage range of 75-300 mg/day, could be considered as a first-line treatment option for the management of AUDs. Its use appears to be safe and well-tolerated, especially in light of very recent findings.

Topics: Alcohol Deterrents; Alcohol-Related Disorders; Fructose; Humans; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Topiramate

Topics: Acamprosate; Alcoholism; Baclofen; Combined Modality Therapy; Ethanol; Fructose; Humans; Naltrexone; Psychotherapy; Secondary Prevention; Socioenvironmental Therapy; Substance Withdrawal Syndrome; Taurine; Topiramate

Alcohol dependence is a major health problem worldwide. Various pharmacological agents have been used in the management of alcohol dependence. This review looks at the role of topiramate and other anticonvulsants in the management of alcohol dependence. Topiramate is the most widely used anticonvulsant in the treatment of alcohol dependence. The literature on topiramate is reviewed and critically analyzed, along with its proposed mechanism of action in alcohol dependence. A review of data available on other anticonvulsants like carbamazepine, oxcarbazepine, sodium valproate, gabapentin and levetiracetam are presented and their potential in the treatment of alcohol dependence is considered, together with future research directions.

Topics: Alcohol-Induced Disorders, Nervous System; Alcoholism; Anticonvulsants; Brain; Brain Chemistry; Fructose; Humans; Mood Disorders; Substance Withdrawal Syndrome; Topiramate

Despite the availability of currently approved medications and various psychosocial therapies, alcohol abuse and dependence are increasingly prevalent in the United States, and carry a significant socioeconomic burden. Recently, the novel anti-epileptic topiramate has shown great promise as a new treatment for this disorder. The objective of this review is to discuss the limitations of the currently available options for treating alcohol dependence, to review the results of clinical trials assessing the efficacy of topiramate in treating alcohol dependence, and to describe the pharmacological characteristics and mechanisms of action of topiramate as related to this indication. We systematically reviewed Medline, EMBASE, Cochran Reviews and PsycINFO search terms included combinations of the terms "pharmacotherapy" "topiramate", "alcoholism" and "alcohol dependence." Searches were last updated 24 October 2008. Currently approved treatments include disulfiram, naltrexone tablets and injection, and acamprosate. Of these, naltrexone has shown the most benefit, however the effect size is small and may reach its most promising potential when combined with medical management. Alternatively, through multiple mechanisms of action, topiramate in clinical trials has demonstrated safety and efficacy in decreasing both craving and withdrawal symptoms and increasing quality of life measures among alcohol-dependent individuals. The findings of this review suggest that topiramate is a promising new option for the treatment of alcohol dependence, and may offer substantial benefits over currently approved medications. While the manufacturer will not pursue approval of an indication for the treatment of alcohol dependence, the drug will soon be available generically, making it more affordable for a greater proportion of the public.

Topics: Alcohol Deterrents; Alcohol Drinking; Alcohol-Induced Disorders; Alcoholism; Anticonvulsants; Fructose; Humans; Substance Withdrawal Syndrome; Topiramate

Topiramate increases GABAergic activity and antagonizes the AMPA/kainate subtype of glutamate receptors. Through these mechanisms of action, topiramate may reduce alcohol and cocaine reward and may reduce alcohol and cocaine craving. Topiramate has been shown to reduce drinking in persons with alcohol dependence, and reduce relapse in stimulant-dependent patients. The current trial was intended to test the ability of topiramate to promote cocaine and alcohol abstinence among patients addicted to both drugs.. The study was a double-blind, placebo-controlled, 13-week trial involving 170 cocaine and alcohol dependent subjects. After achieving a period of cocaine and alcohol abstinence, subjects were randomized to topiramate, 300 mg daily, or identical placebo capsules. In addition, subjects received weekly individual psychotherapy. Primary outcome measures included self-reported alcohol and cocaine use, and thrice weekly urine drug screens. Secondary outcome measures included cocaine and alcohol craving, Addiction Severity Index results, cocaine withdrawal symptoms, and clinical global improvement ratings.. Topiramate was not better than placebo in reducing cocaine use on the a priori primary outcome measure, or in reducing alcohol use. Topiramate was not better than placebo in reducing cocaine craving. Topiramate-treated subjects, compared to placebo-treated subjects, were more likely to be retained in treatment and more likely to be abstinent from cocaine during the last three weeks of the trial. Subjects who entered treatment with more severe cocaine withdrawal symptoms responded better to topiramate.. Topiramate plus cognitive behavioral therapy may reduce cocaine use for some patients with comorbid cocaine and alcohol dependence.

Topics: Adolescent; Adult; Aged; Alcoholism; Anticonvulsants; Behavior, Addictive; Cocaine-Related Disorders; Cognitive Behavioral Therapy; Combined Modality Therapy; Double-Blind Method; Female; Fructose; Humans; Male; Middle Aged; Patient Compliance; Secondary Prevention; Severity of Illness Index; Substance Withdrawal Syndrome; Topiramate

Study aims were threefold: (i) to determine the feasibility, potential efficacy and safety of topiramate as an aid to smoking cessation; (ii) to examine potential predictors of abstinence including gender; and (iii) to explore topiramate's effects on tobacco withdrawal and post-cessation weight gain.. Randomized, double-blind, placebo-controlled, 11-week clinical trial with a 6-week dosage titration period and 5 weeks of maintenance treatment.. Single-site, out-patient, randomized clinical trial.. Thirty-eight adult male and 49 female chronic smokers who smoked an average of > 10 cigarettes per day and who were motivated to try to quit smoking.. Random assignment to receive either topiramate (n = 43) up to 200 mg daily in divided doses or placebo (n = 44) orally combined with brief counseling over an 11-week period.. Carbon monoxide (CO)-confirmed 4-week prolonged abstinence rate during weeks 8-11. Changes in tobacco withdrawal, body weight and safety parameters were also assessed.. Overall, no significant increase in the prolonged abstinence rate was detected, but logistic regression analysis indicated significant gender-specific differences. Men treated with topiramate were nearly 16 times more likely to quit smoking than women on topiramate [37.5% versus 3.7%; odds ratio (OR) = 15.6; P = 0.016] and were roughly four times more likely to quit smoking than placebo-treated men (37.5% versus 13.6%; OR = 3.8; P = 0.098). Topiramate-treated men reported significantly lower tobacco withdrawal scores than both women taking topiramate and men on placebo. On average, male cessators on placebo gained 3.30 kg, whereas topiramate led to a 0.72 kg weight loss (P = 0.03). Study discontinuation rates due to adverse events (AEs) were significantly higher in the topiramate group (topiramate 23% versus placebo 2%). The most commonly reported AEs in the topiramate arm were paraesthesia, fatigue, difficulty with concentration/attention and nervousness.. Topiramate produced gender-specific effects on smoking cessation. Male smokers had markedly greater quit rates than female smokers and men were roughly four times more likely to quit smoking when treated with topiramate as compared to placebo. Topiramate was fairly well tolerated, although higher discontinuation rates were seen. Topiramate's triple effects aiding smoking abstinence, attenuating nicotine withdrawal and preventing post-cessation weight gain might make it a promising agent for treating tobacco addiction, at least in men.

Topics: Adult; Dose-Response Relationship, Drug; Epidemiologic Methods; Female; Fructose; Humans; Male; Neuroprotective Agents; Sex Factors; Smoking Cessation; Substance Withdrawal Syndrome; Topiramate; Weight Gain

To evaluate anticraving action and tolerability of topiramate in cocaine user treatment.. Male users of inhaled cocaine which met criteria for cocaine dependence (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) were selected for outpatient 12-week, open label trial with topiramate; individual dosage ranged between 25-300 mg/day. Main clinical variables were abstinence rate, craving intensity, frequency and duration, adherence, dropouts, side effects and impulsivity measure through Barratt Impulsivity Scale. Patients received assertive strategic counseling for abstinence assistance and medication monitoring evaluation every two weeks. Comparative analysis was made with intention to treat, missing values were replaced (last observation carried forward), and significance level was 5%.. Adherence to treatment was 57% (at least three evaluations), 32% dropped out (one evaluation). There were no severe side effects. Negative test average was 25.4% (31.2). Significant reduction in craving intensity and duration was observed in 25% of the sample. No statistical significant reduction in craving frequency was observed in 7.1%. Increase in frequency was observed in 10.7% and 82.1% did not present any variation. No significant statistical variations in Barratt Impulsivity Scale or in the total score were found in the final evaluation when compared to baseline.. More randomized placebo-controlled trials with topiramate for cocaine dependants should be performed to evaluate preliminary evidence.

Topics: Adult; Ambulatory Care; Behavior, Addictive; Cocaine-Related Disorders; Fructose; Humans; Male; Medication Adherence; Neuroprotective Agents; Patient Dropouts; Self-Assessment; Substance Withdrawal Syndrome; Topiramate

Clinical studies have shown that topiramate, an anticonvulsant medication, may be effective as a treatment for smoking cessation. However, less is known about topiramate effects on nicotine withdrawal and craving and its interactions with a smoked cigarette.. The objective of this study was to investigate the effects of topiramate treatment on abstinence-related nicotine withdrawal, cue-induced cigarette craving, and the acute effects of a smoked cigarette.. Fifteen female and 25 male cigarette smokers were randomly assigned to 9-day treatment with topiramate (final titration dose, 75 mg/day) or placebo. On the last day of treatment, after a 3-h smoke-free abstinence period, participants were evaluated for symptoms of nicotine withdrawal and then underwent cigarette and neutral cue reactivity testing. Thirty minutes after completing cue exposure testing, participants were then evaluated for the acute effects of a smoked cigarette. Cue reactivity and acute smoking measures included subjective ratings of cigarette craving and withdrawal and physiological measures of skin conductance and temperature, heart rate, and blood pressure. In addition, smoking topography was measured using a puff volume apparatus.. Topiramate treatment enhanced subjective ratings of withdrawal after the 3-h abstinence period and reduced pre-cue skin conductance levels. Cigarette cue exposure resulted in a moderate increase in craving, which was unaffected by treatment. Topiramate treatment enhanced the rewarding effects of a smoked cigarette, even while participants smoked less per puff and achieved lower plasma nicotine levels.. Results suggest that topiramate enhances both nicotine withdrawal and reward. These findings question the utility of topiramate treatment for smoking cessation.

Topics: Adult; Behavior, Addictive; Blood Pressure; Cues; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fructose; Ganglionic Stimulants; Heart Rate; Humans; Male; Middle Aged; Neuroprotective Agents; Nicotine; Nicotinic Agonists; Smoking; Smoking Cessation; Substance Withdrawal Syndrome; Topiramate

Benzodiazepines are the standard pharmacotherapies for ethanol detoxification, but concerns about their abuse potential and negative effects upon the transition to alcohol abstinence drive the search for new treatments. Glutamatergic activation and glutamate receptor up-regulation contribute to ethanol dependence and withdrawal. This study compared 3 antiglutamatergic strategies for ethanol detoxification with placebo and to the benzodiazepine, diazepam: the glutamate release inhibitor, lamotrigine; the N-methyl-D-aspartate glutamate receptor antagonist, memantine; and the AMPA/kainite receptor inhibitor, topiramate.. This placebo-controlled randomized single-blinded psychopharmacology trial studied male alcohol-dependent inpatients (n=127) with clinically significant alcohol withdrawal symptoms. Subjects were assigned to 1 of 5 treatments for 7 days: placebo, diazepam 10 mg TID, lamotrigine 25 mg QID, memantine 10 mg TID, or topiramate 25 mg QID. Additional diazepam was administered when the assigned medication failed to suppress withdrawal symptoms adequately.. All active medications significantly reduced observer-rated and self-rated withdrawal severity, dysphoric mood, and supplementary diazepam administration compared with placebo. The active medications did not differ from diazepam.. This study provides the first systematic clinical evidence supporting the efficacy of a number of antiglutamatergic approaches for treating alcohol withdrawal symptoms. These data support the hypothesis that glutamatergic activation contributes to human alcohol withdrawal. Definitive studies of each of these medications are now needed to further evaluate their effectiveness in treating alcohol withdrawal.

Topics: Adult; Alcoholism; Arousal; Autonomic Nervous System; Depression; Diazepam; Excitatory Amino Acid Antagonists; Fructose; GABA Modulators; Humans; Inpatients; Lamotrigine; Male; Memantine; Middle Aged; Mood Disorders; Substance Withdrawal Syndrome; Topiramate; Triazines

Topiramate, an anticonvulsant medication, may be effective as a treatment for alcohol and cocaine addiction. While a recent clinical study has demonstrated the potential utility of topiramate for smoking cessation in alcohol-dependent smokers, the effects of topiramate on tobacco addiction have not been systematically examined in humans.. To determine topiramate's effects on acute physiological and subjective responses to intravenous (IV) nicotine in overnight abstinent smokers.. Seven male and five female smokers participated in a double-blind, placebo-controlled, crossover study, which consisted of one adaptation and three experimental sessions. Before each session, participants were treated orally with either a single 25 or 50 mg topiramate dose or with placebo. Starting 2 h following the medication treatment, participants received an IV saline injection, followed by 0.5 and 1.0 mg/70 kg IV nicotine.. Topiramate treatment at 50 mg, compared to 25 mg or placebo, attenuated heart rate increases induced by nicotine. Topiramate, compared to placebo, enhanced the ratings of subjective effects from nicotine including "drug strength," "good effects," "head rush," and "drug liking." Topiramate treatment did not affect performance on the Stroop test.. These results suggest that topiramate may enhance the subjective effects of nicotine and attenuate the heart rate response to nicotine. While the exact mechanisms are unclear, enhancement of the dopaminergic system and attenuation of the noradrenergic system may mediate the topiramate's effects on the subjective and cardiovascular responses to nicotine, respectively. The utility of topiramate for smoking cessation needs to be examined further in controlled clinical trials.

Topics: Administration, Oral; Adult; Arousal; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fructose; Heart Rate; Humans; Infusions, Intravenous; Male; Middle Aged; Neuropsychological Tests; Nicotine; Smoking Cessation; Substance Withdrawal Syndrome; Tobacco Use Disorder; Topiramate

Nucleus accumbens plays an important role in opioid addiction. Topiramate, increases postsynaptic gamma-aminobutyric acid receptor activity and antagonizes glutamatergic activity. Brain-derived neurotrophic factor (BDNF), which plays a key role in synaptic plasticity, is produced from proBDNF. The aim of this study is to investigate the effects of 100 µM topiramate applied into the lateral ventricle or nucleus accumbens on naloxone-induced morphine withdrawal and the BDNF/proBDNF ratio in the frontal cortex.. In the study, 36 adult male Wistar rats weighing 250-350 g were used. Morphine dependence was created with morphine pellets following guide cannula implantations. Withdrawal findings were evaluated in naloxone-induced morphine withdrawal syndrome following topiramate administration, and locomotor activity measurements were performed simultaneously. The brains of sacrificed animals were removed for determination of BDNF/proBDNF ratio.. Topiramate administered by either route significantly suppressed the number of jumps in morphine withdrawal. Topiramate applied into the nucleus accumbens significantly reduced stereotypical behavior in morphine withdrawal, but did not cause any changes in other locomotor activity behaviors. Topiramate applied into the lateral ventricle significantly decreased the BDNF/proBDNF ratio, whereas administered into the nucleus accumbens significantly increased this ratio.. The findings of this study indicate that topiramate administered into the lateral ventricle and nucleus accumbens reduces naloxone-induced morphine withdrawal symptoms, stereotypical locomotor activity, and changes the BDNF/proBDNF ratio.

Topics: Animals; Brain-Derived Neurotrophic Factor; Male; Morphine; Naloxone; Nucleus Accumbens; Rats; Rats, Wistar; Substance Withdrawal Syndrome; Topiramate

In the last decade, prescription of anticonvulsants for treatment of low back pain (LBP) increased 4-fold. Among them, topiramate has frequent side effects and a mechanism of action that is not fully understood. The authors describe a 65-year-old woman with dependence on topiramate prescribed for chronic LBP and discuss how she was successfully weaned off topiramate using duloxetine. A significant agonistic effect by topiramate on α-2 adrenergic receptors in the brain likely accounts for the symptoms of withdrawal that were seen. We attribute the resolution of her topiramate withdrawal symptoms to reduced norepinephrine (NE) release, a known effect of duloxetine administration.

Topics: Aged; Anticonvulsants; Duloxetine Hydrochloride; Female; Humans; Low Back Pain; Receptors, Adrenergic, alpha-2; Substance Withdrawal Syndrome; Topiramate; Treatment Outcome

Anxiety disorders are associated with increased impairments in psychosocial functioning, work productivity and health-related quality of life. In addition, anxiety is a common symptom of ethanol withdrawal and it strongly contributes to relapse. Benzodiazepines are frequently prescribed for relief of anxiety and ethanol withdrawal symptoms but considerable side effects, such sedation, tolerance and dependence, are observed during treatment. Therefore, better drugs are needed for the treatment of anxiety states. The purpose of this study was to investigate whether topiramate would reduce basal levels of anxiety and ethanol-withdrawn induced anxiety in male rats; the elevated plus maze (EPM) was used as an animal model of anxiety. In Experiment 1, topiramate (0, 10, and 40 mg/kg, i.g.) and diazepam (1 mg/kg, i.p.) was acutely and repeatedly administered to naive rats. In Experiments 2 and 3, topiramate (0 or 40 mg/kg, i.g.) was acutely and chronically administered in early (72 hr after ethanol removal) and protracted (21 days after ethanol removal) ethanol-withdrawn rats, respectively. Acute and repeated topiramate treatment induced anxiolytic-like effects in naive rats. Early ethanol withdrawal increased anxiety, and acute topiramate administration counteracted the anxiogenic-like effects of ethanol removal. Protracted withdrawal did not produce lasting changes in anxiety but topiramate was equally effective at reducing anxiety in ethanol-withdrawn and control animals. Importantly, no signs of tolerance to the anxiolytic effects of topiramate were observed. In conclusion, these data support a role for topiramate in the treatment of basal levels of anxiety and ethanol withdrawal-induced anxiety. (PsycINFO Database Record

Topics: Animals; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Behavior, Animal; Diazepam; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Fructose; Male; Rats; Rats, Wistar; Substance Withdrawal Syndrome; Topiramate

Morphine withdrawal is associated with a hyperactivity of locus coeruleus (LC) neurons by an elevated glutamate neurotransmission in this nucleus. We postulate that reductions in the amount of glutamate in the LC by enhancing its reuptake or inhibiting its release could attenuate the behavioral and cellular consequences of morphine withdrawal.. We investigated the effect of chronic treatment with ceftriaxone (CFT), an excitatory amino acid transporter (EAAT2) enhancer, and acute administration of topiramate (TPM), a glutamate release inhibitor, on morphine withdrawal syndrome and withdrawal-induced glutamate receptor (GluR) desensitization in LC neurons from morphine-dependent rats.. Morphine withdrawal behavior was measured after naltrexone administration in rats implanted with a morphine (200 mg kg(-1)) emulsion for 3 days. GluR desensitization in the LC was assessed by performing concentration-effect curves for glutamate by extracellular electrophysiological recordings in vitro.. Treatments with CFT or TPM reduced, in a dose-related manner, the total behavioral score of naltrexone-precipitated morphine withdrawal. CFT and TPM, at doses that were effective in behavioral tests, also reduced the induction of GluR desensitization normally occurring in LC neurons from morphine-dependent rats. Acute treatment with the specific EAAT2 inhibitor dihydrokainic acid (DHK) prevented the effect of CFT on withdrawal syndrome and GluR desensitization. Perfusion with TPM inhibited KCl-evoked but not glutamate-induced activation of LC neurons in vitro.. Our results suggest that a reduction of synaptic concentrations of glutamate by enhancing EAAT2-mediated uptake or inhibiting glutamate release alleviates the behavioral response and the cellular changes in the LC during opiate withdrawal.

Topics: Analgesics, Opioid; Animals; Ceftriaxone; Fructose; Glutamic Acid; Locus Coeruleus; Male; Morphine Dependence; Neurons; Rats; Rats, Sprague-Dawley; Receptors, Glutamate; Substance Withdrawal Syndrome; Topiramate

The effect of topiramate (topamax) on the electrical activity of frontal cortical neurons of neoencephalon was studied by microelectrode techniques in rats. Topiramate upon acute intraperitoneal administration and microionophoretic application dose-dependently reduced the frequency of spike activity within 17 - 30 min after injection at a dose of 40 and 80 mg/kg. At the same time, the agent did not change the membrane rest potential, and the magnitude and form of action potentials. Microionophoretically applied topiramate decreased the excitatory response to electroosmotically applied ethanol at "small doses" (ejected current < 50 nA) and enhanced the neuronal depression induced by ethanol at "large doses" (ejected current > 50 nA). It is suggested that the attenuation of alcohol seeking behavior observed after topiramate administration is due to suppression of ethanol activating effects in neoencephalon neurons, while the alleviation of alcohol withdrawal is associated with the central depressant activity.

Topics: Action Potentials; Alcoholism; Animals; Ethanol; Frontal Lobe; Fructose; Injections, Intraperitoneal; Male; Microelectrodes; Neocortex; Neuroprotective Agents; Rabbits; Rats; Rats, Wistar; Stereotaxic Techniques; Substance Withdrawal Syndrome; Topiramate

This study examined the actions of pregabalin and topiramate on behavioural and gene transcription alterations induced by spontaneous cannabinoid withdrawal in mice. Tolerance was induced in mice by administration of CP-55,940 (0.5 mg/kg/12 hours; i.p.; 7 days). Behavioural assessment of spontaneous cannabinoid withdrawal was performed by measuring motor activity, somatic signs and anxiety-like behaviour on days 1 and 3 after cessation of treatment with CP-55,940. On days 1-3 of cannabinoid withdrawal, mice received pregabalin (40 mg/kg/12 hours; p.o.) or topiramate (50 mg/kg/12 hours; p.o.) and their actions on signs of withdrawal and anxiety-like behaviour were evaluated. The administration of CP-55,940 decreased rectal temperature and motor activity on day 1. On day 1 after interruption of cannabinoid administration, motor activity and the number of rearings increased compared with control group. Anxiety-like behaviour induced by cessation of cannabinoid treatment increased significantly on days 1 and 3 of withdrawal. The administration of pregabalin or topiramate blocked the motor signs and reduced significantly anxiety-like behaviour. Cannabinoid withdrawal decreased tyrosine hydroxylase (TH) gene expression in the ventral tegmental area and µ-opioid receptor gene expression in the nucleus accumbens (NAcc) and increased CB1 receptor gene expression in the NAcc. Treatment with topiramate or pregabalin blocked the decrease of TH and the increase of CB1 gene expressions induced by cannabinoid withdrawal. Both drugs failed to alter µ-opioid receptor gene expression. These results suggest that pregabalin and topiramate may result useful for the treatment of anxiety-like behaviour and motor symptoms associated with spontaneous cannabinoid withdrawal.

Topics: Analysis of Variance; Animals; Anticonvulsants; Anxiety; Behavior, Animal; Body Temperature; Cannabinoids; Cyclohexanols; Dose-Response Relationship, Drug; Drug Tolerance; Fructose; gamma-Aminobutyric Acid; Male; Marijuana Abuse; Mice; Models, Animal; Motor Activity; Nucleus Accumbens; Pregabalin; Receptor, Cannabinoid, CB1; Receptors, Opioid, mu; Substance Withdrawal Syndrome; Topiramate; Transcription, Genetic; Tyrosine 3-Monooxygenase; Ventral Tegmental Area

Topics: Carbon Monoxide; Cues; Fructose; Humans; Neuroprotective Agents; Randomized Controlled Trials as Topic; Smoking; Smoking Cessation; Smoking Prevention; Substance Withdrawal Syndrome; Topiramate

Topics: Adrenergic beta-Antagonists; Analgesics; Anticonvulsants; Clinical Protocols; Clinical Trials as Topic; Drug Administration Schedule; Electric Stimulation Therapy; Fructose; Headache Disorders; Humans; Neuromuscular Blocking Agents; Substance Withdrawal Syndrome; Topiramate; Valproic Acid

Topics: Adult; Anti-Obesity Agents; Feeding Behavior; Fructose; Humans; Male; Obesity; Substance Withdrawal Syndrome; Topiramate; Weight Gain

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: Acamprosate; Alcohol Deterrents; Alcoholism; Antidepressive Agents; Disulfiram; Fructose; Humans; Naltrexone; Substance Withdrawal Syndrome; Taurine; Topiramate

Topiramate, a novel anticonvulsant drug, has CNS depressant activity including enhancement of GABAergic inhibitory synaptic transmission. Drugs of this pharmacological spectrum might have utility in assuaging drug addiction. This study analyzes the ability of TPM to reduce withdrawal signs in the kindling model of ethanol dependence: chronic intermittent ethanol (CIE) rats. After CIE, persistent withdrawal signs are shown by an increased seizure susceptibility to the convulsant drug pentylenetetrazol and increased anxiety measured on the elevated plus-maze. Topiramate increased significantly the PTZ seizure threshold in CIE but not in control rats. On the elevated plus-maze, Topiramate was markedly more effective in CIE rats than in controls. Topiramate may have a therapeutic efficacy in treating alcohol withdrawal symptoms.

Topics: Animals; Ethanol; Fructose; Male; Rats; Rats, Sprague-Dawley; Seizures; Substance Withdrawal Syndrome; 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

There is an increasing interest in anticonvulsants for the treatment of benzodiazepine withdrawal symptoms. The new anticonvulsant compound topiramate seems to be an especially promising drug for this indication. It acts, among others, as an AMPA antagonist, which may be responsible in part for its anticonvulsant efficacy, but may also modulate the withdrawal-induced activation of noradrenergic neurons in the locus coeruleus, which are related to some behavioural effects of benzodiazepine withdrawal. A case is presented of a rapid benzodiazepine-withdrawal treated successfully with topiramate.

Topics: Adult; Anticonvulsants; Benzodiazepines; Fructose; Humans; Male; Receptors, AMPA; 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