Low-Dose Topiramate in Alcohol Dependence: A Single-Blind, Placebo-Controlled Study

Introduction:Topiramate (TOP) and anticonvulsants in general are considered safe and effective drugs for the treatment of alcohol dependence, even though TOP-induced adverse events are quite common, especially for high initial doses or if titration to 300 mg/d is too rapid. The aim of the present study was to assess the efficacy and tolerability profile of low-dose TOP for relapse prevention. METHODS: After detoxification, 52 patients were randomized into 2 groups as follows: 26 patients received 100 mg of TOP (oral, twice daily), titrated over 2 weeks, and 26 patients received placebo (PLA). Both groups underwent rehabilitation twice a week. RESULTS: After 6 weeks of treatment, compared with the PLA group, patients receiving TOP showed the following: (1) fewer drinking days (P < 0.05); (2) less daily alcohol consumption (P < 0.05); (3) more days of treatment (P < 0.05); (4) reduced levels of craving (Obsessive-Compulsive Drinking Scale) and withdrawal symptoms (Clinical Institute Withdrawal Assessment for Alcohol-Revised); and (5) improvement of anxiety, depression, and obsessive-compulsive symptom severity (Symptom Check List 90 Revised). CONCLUSIONS: Despite the small sample size and the short follow-up period, the present PLA-controlled study demonstrated the potential usefulness of TOP, even when administered at a dosage of 100 mg/d, for the treatment of detoxified alcohol-dependent subjects, confirming results from previous studies testing higher doses of TOP

Low-dose topiramate in alcohol dependence: a randomized, double-blind, placebo-controlled trial

The anticonvulsivant topiramate could be useful in the treatment of Alcohol Withdrawal Syndrome since it has the ability to suppress glutamatergic input, to facilitate GABAA-mediated inhibitory impulse, to block sodium and calcium channels, and to facilitate potassium conductance [1]. Several studies have demonstrated the safety and efficacy of topiramate in promoting abstinence and relapse prevention [2]. Purpose of the study: The aim of this randomized, doubleblind, placebo-controlled trial was to compare topiramate at low dosage with placebo on alcohol drinking indices and craving in detoxified alcohol dependent subjects. Psychiatric symptomatology, quality of life and clinical global improvement have also been investigated. Methods: 52 detoxified Alcohol Dependent (DSM-IV-TR) outpatients (M/F 2/1, mean age 46.1±11.1; mean daily drinks 8.3±3.2; mean years of addiction 6.8±3.7) were recruited and subsequently randomized into two groups, respectively receiving topiramate (100 mg/die) (n = 26) or placebo (n = 26). The level of craving for alcohol was evaluated through a 10-cm Visual Analogue Scale (VASc) and the Italian version of the Obsessive and Compulsive Drinking Scale (OCDS). Psychiatric symptomatology was evaluated through the Symptom Check List 90 Revised (SCL-90-R), withdrawal symptoms through the Clinical Institute Withdrawal Assessment of Alcohol-Revised (CIWA-Ar), quality of life through the Quality of Life Index 74 (QL-INDEX-74) and clinical global improvement using the Clinical Global Impression (CGI). Subjects were assessed at the beginning of the treatment (T0) and after 30 (T1), 90 (T2) and 180 (T3) days. Results: The survival function showed that patients treated with topiramate remained abstinent from any alcohol amount for a longer time with respect to placebo (Z = −2.197; p<0.05). The improvement of alcohol drinking indices and craving scores was significant in both groups but higher in the topiramate than in the placebo one (OCDS: p<0.05; VASc: p<0.05). Withdrawal total scores as measured by the CIWA-Ar were significantly reduced in the topiramate group (F = 3.8; p<0.025) and in the placebo group (F = 3.2; p<0.025). Significant improvements (p<0.05) for both groups were seen at the CGI and the QL-INDEX-74. The SCL-90-R general index of ‘Positive Symptom Total’ was significantly reduced only in the topiramate group (F = 3.41, p <0.05). The number of patients dropped-out from the study for adverse events was not different between groups. No clinically relevant differences between groups were seen in the mean change from baseline for any vital signs, ECGs, haematological, or clinical chemistry parameters. Conclusions: Topiramate resulted to be more efficacious than placebo for both the improvement of withdrawal symptomatology and the reduction of relapses. Furthermore, it showed efficacy in reducing craving, obsession and compulsion connected with alcohol intake, the severity of global psychopathology and in improving the quality of life. Moreover, the use of topiramate at low dosage could increase the number of subjects remaining in treatment, given the reduced possibility of adverse events. In conclusion, our results continue to provide evidence that topiramate is a safe and effective treatment, which could represent an alternative option beyond the already approved agents for the treatment of Alcohol Dependence

Low-dose topiramate in alcohol dependence a single-blind, placebo-controlled study

Introduction: Topiramate (TOP) and anticonvulsants in general are considered safe and effective drugs for the treatment of alcohol dependence, even though TOP-induced adverse events are quite common, especially for high initial doses or if titration to 300 mg/d is too rapid. The aim of the present study was to assess the efficacy and tolerability profile of low-dose TOP for relapse prevention. Methods: After detoxification, 52 patientswere randomized into 2 groups as follows: 26 patients received 100 mg of TOP (oral, twice daily), titrated over 2 weeks, and 26 patients received placebo (PLA). Both groups underwent rehabilitation twice a week. Results: After 6 weeks of treatment, compared with the PLA group, patients receiving TOP showed the following: (1) fewer drinking days (P < 0.05); (2) less daily alcohol consumption (P < 0.05); (3) more days of treatment (P < 0.05); (4) reduced levels of craving (Obsessive-Compulsive Drinking Scale) and withdrawal symptoms (Clinical Institute Withdrawal Assessment for Alcohol-Revised); and (5) improvement of anxiety, depression, and obsessive-compulsive symptom severity (Symptom Check List 90 Revised). Conclusions: Despite the small sample size and the short follow-up period, the present PLA-controlled study demonstrated the potential usefulness of TOP, even when administered at a dosage of 100 mg/d, for the treatment of detoxified alcohol-dependent subjects, confirming results from previous studies testing higher doses of TOP

Assessing the validity and reliability of the Turkish versions of craving beliefs and beliefs about substance use questionnaire in patients with heroin use disorder: demonstrating valid tools to assess cognition-emotion interplay

Background: Cognitions associated with craving and substance use are important contributors for the psychological theories of Substance use disorders (SUD), as they may affect the course and treatment. In this study, we aimed to validate Turkish version of two major scales 'Beliefs About Substance Use'(BSU) and 'Craving Beliefs Questionnaire'(CBQ) in patients with heroin use disorder and define the interaction of these beliefs with patient profile, depression and anxiety symptoms, with an aim to use these thoughts as targets for treatment. Methods: One hundred seventy-six inpatients diagnosed with heroin use disorder and 120 participants in the healthy comparison group were evaluated with CBQ, BSU, Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and sociodemographic data questionnaire. Patient group was also evaluated with Addiction Profile Index. Reliability and validity analysis for scales were conducted. Linear regression analysis was conducted to evaluate the determinants of BSU and CBQ scores. Results: Cronbach alpha level was 0.93 for BSU and 0.94 for CBQ. Patient group showed significantly higher CBQ, BSU, BAI and BDI scores (p < 0.001). BSU score significantly correlated with API-substance use profile score, API-diagnosis, BAI, BDI and CBQ (p < 0.005), whereas CBQ scores significantly correlated with API-diagnosis, API-impact on life, API-craving, API-total score, BSU, BAI, BDI and amount of cigarette smoking (p < 0.002). Number of previous treatments and age of onset for substance use were not correlated with either BSU or CBQ. BAI and BDI scores significantly predicted BSU score, however only BDI score predicted CBQ score (p < 0.003). Conclusions: Craving beliefs were highly correlated with addiction profile. Anxiety and depression are significant modulators for patients' beliefs about substance use and depression is a modulator for craving and maladaptive beliefs, validating emotion-cognition interplay in addiction

Rehabilitating the addicted brain with transcranial magnetic stimulation

Substance use disorders (SUDs) are one of the leading causes of morbidity and mortality worldwide. In spite of considerable advances in understanding the neural underpinnings of SUDs, therapeutic options remain limited. Recent studies have highlighted the potential of transcranial magnetic stimulation (TMS) as an innovative, safe and cost-effective treatment for some SUDs. Repetitive TMS (rTMS) influences neural activity in the short and long term by mechanisms involving neuroplasticity both locally, under the stimulating coil, and at the network level, throughout the brain. The long-term neurophysiological changes induced by rTMS have the potential to affect behaviours relating to drug craving, intake and relapse. Here, we review TMS mechanisms and evidence that rTMS is opening new avenues in addiction treatments