Marco Faccini

Tobacco Addiction and Smoking Status in Heroin Addicts under Methadone vs. Buprenorphine Therapy

Aims of the present investigation were: (i) to assess the prevalence of current smokers and relative smoking status among a large number of heroin addicts attending opioid-substitution therapy prevalence; (ii) to evaluate the relationship between the type (methadone, buprenorphine) and dosage of opioid substitution therapy and nicotine dependence. Three hundred and five (305) heroin addicts under opioid-substitution therapy were recruited at five Addiction Units. All participants completed a questionnaire assessing sociodemographic information, type and dose of opioid-substitution therapy, smoking history and status, Fagerström Test for Nicotine Dependence (FTND), and the Zung Self-Rating Depression scale (SDS). 298 subjects, out of 305 (97.2%) were smokers, with an average of 20.5 cigarette/day and a median FTND of 6. Our data confirmed the high prevalence of smokers among heroin addicts, the highest described in the literature to date among heroin addicts under substitution therapies, without any significant difference between methadone vs. buprenorphine therapy groups. There was no correlation between dose of methadone or buprenorphine and average number of cigarettes/day. Patients in substance abuse treatment very frequently smoke cigarettes and often die of tobacco-related diseases. Substance abuse treatment programs too often ignore tobacco use. We hope that these findings will help to incorporate smoking cessation in substance abuse treatments.

Isolated Presence of Antibody to Hepatitis B Core Antigen in Injection Drug Users: Do They Need to Be Vaccinated?

In a study of 497 injection drug users who had isolated presence of antibody to hepatitis B core antigen (anti-HBc) at the time of enrollment, 404 (81%) retained this condition after a mean of 49 months of follow-up, during which time no new hepatitis B surface antigen marker was detected. These findings support the hypothesis that patients with isolated presence of anti-HBc have strong resistance to reinfection and do not need vaccination.

Quality of life in a cohort of high-dose benzodiazepine dependent patients.

BACKGROUND Benzodiazepines (BZD) are among the most widely prescribed drugs in developed countries. Since BZD can produce tolerance and dependence even in a short time, their use is recommended for a very limited time. However, these recommendations have been largely disregarded. The chronic use of BZD causes a number of serious side effects, i.e., cognitive impairment, falls, traffic accidents, dependence and tolerance. The aim of the present study was to evaluate quality of life (QoL) in a cohort of 62 consecutive high-dose BZD-dependent patients seeking a BZD detoxification. METHODS Patients seeking BZD detoxification were evaluated using the General Health Questionnaire (GHQ-12) and the short form-36 questionnaire (SF-36). RESULTS Patients showed a significant reduction of QoL as measured by either SF-36 or GHQ-12. In particular, the greater impairment was observed in the items exploring physical and emotional status. Physical functioning was the item more influenced by the length of BZD abuse. Female patients showed a greater reduction of QoL compared to male, at least in some of the explored items. Social functioning scores were greatly reduced. CONCLUSIONS The present study shows for the first time that high-doses BZD dependent patients have a reduced QoL and a reduced social functioning, along with high levels of psychological distress.

Multifocal cognitive dysfunction in high-dose benzodiazepine users: a cross-sectional study

Benzodiazepines (BZDs) are the most widely prescribed drug class in developed countries, but they have high potential for tolerance, dependence and abuse. Cognitive deficits in long-term BZD users have long been known, but previous results might have been biased by patients’ old age, coexisting neurological or psychiatric conditions or concurrent alcohol or psychotropic drug dependence. The study was aimed to explore the neuropsychological effect of high-dose BZD dependence, which represents an emerging addiction phenomenon. We recruited a group of high-dose BZD users with neither neurological or psychiatric comorbidity except anxiety or depression nor concurrent alcohol or psychotropic drug dependence. They underwent a battery of cognitive tests to explore verbal, visuospatial memory, working memory, attention, and executive functions. All the neuropsychological measures were significantly worse in patients than controls, and some of them were influenced by the BZD cumulative dose. The severity of depression and anxiety had a minimal influence on cognitive tests. Patients with high-dose BZD intake show profound changes in cognitive function. The impact of cognition should be considered in this population of patients, who may be involved in risky activities or have high work responsibilities.

Lormetazepam addiction: data analysis from an Italian medical unit for addiction

Background The purpose of this study was to determine, in the context of a hospital addiction unit, which benzodiazepines were abused and to look for correlations with the characteristics of detoxified patients. Methods A retrospective study was carried out using the database of hospital admissions to the addiction unit for detoxification from 2003 to 2010. Results Of 879 admissions to the addiction unit during the seven-year period, 281 were for benzodiazepines. The percentage of patients addicted only to benzodiazepines was higher among females than males. Benzodiazepine consumption had started as a drug addiction behavior in only 10% of cases. The main sources of prescription identified were general practitioners (52% of cases) or compliant pharmacists (25%). Overall, 15 different benzodiazepines were abused, with lormetazepam being the most commonly used (by 123 patients, 43.8% of the total). Conclusion Our data show that, outside the population of multidrug addicts, there is an underestimated group of chronic benzodiazepine consumers who are often not referred to medical institutions for treatment. Even in the group of patients addicted to one substance only, we observed an abnormal number of requests for detoxification from lormetazepam, which appears to be more “popular” than other benzodiazepines. This drug should be prescribed according to stricter criteria and submitted to closer control.

Focal nonconvulsive seizures during detoxification for benzodiazepine abuse

Chronic benzodiazepine (BDZ) abuse is currently treated with detoxification using a low-dose flumazenil infusion, a relatively recently developed and promising procedure. Given the possibility reported in the literature of the occurrence of generalized seizures during therapeutic BDZ detoxification, we usually administer preventive antiepileptic drug (AED) therapy. We describe two patients with no previous history of seizures or evidence of intracerebral lesions who, during detoxification for benzodiazepine abuse, developed repetitive focal nonconvulsive seizures instead of generalized seizures, even with appropriate doses of preventive AED therapy. There are no previous reported cases of focal nonconvulsive seizures occurring during this procedure or, more generally, during abrupt BDZ discontinuation. The cases we describe suggest that during detoxification for BDZ abuse, not only generalized, but also focal nonconvulsive seizures may occur. In this context, the focal seizures probably result from a diffuse decrease in the seizure threshold (caused by a generalized excitatory rebound), which may trigger focal seizures arising from cortical regions with higher intrinsic epileptogenicity. Detoxification for benzodiazepine abuse, even if performed with adequate-dosage AED treatment, may not be as safe a procedure as previously considered, because not only convulsive, but also nonconvulsive seizures may occur and go unnoticed. It is therefore strongly advisable to perform this detoxification under close medical supervision and to maintain a low threshold for EEG monitoring in the event of sudden onset of behavioral changes.

Intravenous flumazenil infusion to treat benzodiazepine dependence should be performed in the inpatient clinical setting for high risk of seizure.

Benzodiazepines (BZD), typically used to treat insomnia and anxiety disorders, are largely prescribed in all medical fields. This widespread use has led to misuse through frequent and often inappropriate consumption and iatrogenic overdosing. The risk of physical dependence, highly related to the duration of treatment and pharmacokinetic profile of BZD, such as its short half-life, varies between 15% and 44% of chronic users (Ashton, 2005). Symptoms related to BZD discontinuation syndrome can be severe and in most cases may preclude the patients stopping the drug. Seizure represents the most severe, although rare, complication of BZD withdrawal (Chouinard, 2004; Marriott and Tyrer, 1993). Although BZD intentional abusers very often have other substance abuse problems (O’brien, 2005), the rising level of addiction from legitimate prescription is largely underestimated. Our opinion origins from the increasing number of patients seeking an inpatient detoxification treatment in our Addiction Unit (up to approximately 50% of clinical admissions). Our target patients are BZD chronic abusers, and applied treatment is based on rapid stopping of BZD under slow flumazenil infusion (FLU-I) for 8–10 days (Gerra et al., 2002). We read with great interest the paper of Hood et al. published in your journal (Hood et al., 2009). The detoxification treatment described in the article is similar to Gerra et al.’s and Quaglio et al.’s (Gerra et al. 2002; Quaglio et al. 2005). We fully agree with Hood et al. that FLU-I appears to be a highly effective treatment resulting in withdrawal discomfort of lesser severity than any other treatment cessation currently available. We also agree that the treatment needs further development before becoming a routine treatment of BZD dependence but, in our opinion, FLU-I is not so safe as suggested by Hood et al. (2009). We would like to stress the seizure risk related to a detoxification protocol, underestimated by both Gerra et al. and Hood et al. During the last 7 years, our group treated 286 chronic users (156 males and 130 females, median age of 42) of high doses of BZD with FLU-I. The median daily dose was 14 times greater than the maximum dose allowed. Congruent with Gerra et al. and Hood et al., patients immediately stopped abusing BDZ (lormetazepam in 54% and lorazepam in 21% of all cases) and rapidly tapered low doses of other BZD (generally clonazepam) in 3 days up to no BZD on day 4. FLU-I (at a rate of 1–2mg/24 h) started on day 1 and lasted up to discharge at day 8–11. We can confirm that symptoms were reported as mild, requests to stop FLU-I were infrequent and only lasted for very few hours; no patients withdrew from the treatment. The high risk of seizure remains the only unresolved problem related to this highly effective treatment. In our experience, we observed seizures in 10 patients, 3.5% of all cases (6 out 10 withdrawn from lormetazepam, 2 from lorazepam, 1 from alprazolam and 1 from zolpidem): 5 patients suffered of tonic-clonic crises (in 1 case repeated) and 5 patients presented with generalized epileptic crises characterized by absence with mild motor signs. All but tonic-clonic cases required a transfer in neurologic unit where symptoms lasted for several days. Seizures happened from day 4 to day 10 of FLU-I. Only 4 out of 10 were dependent from other substances (2 out 4 were heavy drinkers, 1 used heroin and 1 misused butalbital) and only 1 patient had an episode of seizure in his anamnesis (withdrawn from lorazepam). In conclusion, FLU-I can be an effective and rapid treatment of BZD overdosing dependence. In our opinion, seizure risk is high and remains an unmet issue. Further studies are needed to prevent this serious complication (perhaps using anticonvulsant prophylaxis or different doses of FLU-I), but, at the moment, we strongly recommend to not use FLU-I in outpatient settings as suggested by Gerra et al. and, partially, by Hood et al.

Megadose bromazepam and zolpidem dependence: two case reports of treatment with flumazenil and valproate.

Megadose Bromazepam and Zolpidem Dependence: Two Case Reports of Treatment with Flumazenil and Valproate Gianluca Quaglio MD a , Marco Faccini MD a , Caroline Victorri Vigneau MD b , Rebecca Casari MD a , Sophie Mathewson MSc a , Manuela Licata MD c & Fabio Lugoboni MD a a Medical Service for Addictive Disorder, Department of Internal Medicine, University of Verona, Verona, Italy b Department of Clinical Pharmacology, Nantes University Hospital, Nantes, France c Forensic Service, University of Modena and Reggio Emilia, Modena, Italy

Slow subcutaneous infusion of flumazenil for the treatment of long-term, high-dose benzodiazepine users: a review of 214 cases

Despite the first reports concerning benzodiazepine dependence being published in the early 1960s literature, the risk of benzodiazepine addiction is still greatly debated. The severe discomfort and life threatening complications usually experienced by long-term benzodiazepine users who suddenly interrupt benzodiazepine intake have led to the development of several detoxification protocols. A successful strategy used by our Addiction Unit is abrupt benzodiazepine cessation by administering flumazenil slow subcutaneous infusion (FLU-SSI) with an elastomeric pump. Although some studies proved the efficacy of flumazenil infusion more than 20 years ago, only a few centres in the world offer this method to their patients. This paper reports the data related to 214 subjects addicted to high doses of benzodiazepine and treated with the FLU-SSI method between 2012 and 2014. This technique is less invasive and requires less nursing intervention than intravenous infusion. Our data support FLU-SSI as a possible efficient strategy for the treatment of patients with long-term, high-dose benzodiazepine addiction, and could become a routine therapy as long as the necessary further studies on dose, duration of infusion and safety issues are carried out.

Determinants of Quality of Life in High-Dose Benzodiazepine Misusers

Benzodiazepines (BZDs) are among the most widely prescribed drugs in developed countries, but they have a high potential for tolerance, dependence and misuse. High-dose BZD misuse represents an emerging addiction phenomenon, but data on quality of life (QoL) in high-dose BZD misusers are scant. This study aimed to explore QoL in high-dose BZD misuse. We recruited 267 high-dose BZD misusers, compared the QoL scores in those who took BZD only to poly-drug misusers, and explored the role of demographic and clinical covariates through multivariable analysis. Our data confirmed worse QoL in high-dose BZD misusers and showed that (a) QoL scores were not negatively influenced by the misuse of alcohol or other drugs, or by coexisting psychiatric disorders; (b) demographic variables turned out to be the most significant predictors of QoL scores; (c) BZD intake significantly and negatively influenced QoL. Physical and psychological dimensions of QoL are significantly lower in high-dose BZD misusers with no significant effect of comorbidities. Our data suggest that the main reason for poor QoL in these patients is high-dose BZD intake per se. QoL should be considered among outcome measures in these patients.