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Official websites use. Share sensitive information only on official, secure websites. This article was submitted to Addictive Disorders, a section of the journal Frontiers in Psychiatry. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. However, by now the prevalence of NMU of gabapentinoids in the general population has not been sufficiently evaluated. The aim of this research paper is to determine the prevalence of prescription GABA analog NMU and associated demographics in five European countries with special detail of Spain. NMURx collects data from the general population in each participating country about NMU of prescription drugs, illicit drugs, and associated demographics. Responses were collected using non-probability quota sampling and post-stratification population weighting was applied to reflect the national distributions of adults, based on age, gender, and census region. Those who non-medically use GABA analogs had a higher prevalence of lifetime chronic pain, lifetime illicit drug use, and previous substance abuse treatment. The main reasons for use were to self-treat pain and other medical conditions. Conclusions: The risk of NMU of gabapentinoids should not be neglected. Subjects with a history of chronic pain and lifetime substance use disorders had an increased risk of NMU of gabapentinoids. Gabapentinoids, pregabalin and gabapentin, are widely used for the treatment of neuropathic pain and epileptic disorders according to the United States US Food and Drug Administration FDA. Both gabapentin and pregabalin have been approved by the European Medicine Agency EMA for neuropathic pain and generalized anxiety disorder, respectively. Additionally, some off-label uses of gabapentinoids include treatment for chronic lower back pain, insomnia, migraine, social phobia, panic disorder, mania, bipolar disorder, and alcohol withdrawal 1 , 2. Gabapentinoids are now among the most commonly prescribed medications in most countries 3. For instance, the overall rate of pregabalin prescriptions use increased from 1. Also, there has been a progressive increase in the reported cases of misuse and dependence to the European Medicines Agency's EudraVigilance database, specifically in subjects with previous history of substance use disorders 3. This in turn increases the GABA levels and decreases other excitatory neurotransmitters 5. This mechanism is associated with their antinociceptive, anticonvulsant, anxiolytic, and sleep-modulating effects 6. Gabapentinoids have significant risks despite their reputation as safe drugs. Sedation, dizziness, gait instability, and feeling of intoxication are quite common side effects; as many as one in three patients taking therapeutic doses experience dizziness or somnolence 7. Although, both substances share some mechanisms of action, they also have some pharmacokinetic differences that could explain differences in their abuse potential; for instance, pregabalin is absorbed more rapidly by oral route, with maximum plasma concentrations attained within 1 h, whereas, maximum plasma concentrations of gabapentin are detected 3—4 h after oral administration. Pregabalin absorption is linear, and gabapentin absorption is saturable non-linear —zero-order- process with less predictable pharmacokinetics. On the other hand, similarities in pharmacokinetics are: both can be given without regard of meals, they do not bind to plasma proteins and both are excreted renally with an elimination half-live of 6 h 7. The linear pharmacokinetics of pregabalin and its greater potency explains its steep dose-response relationship and differences in abuse potential and severe adverse events as respiratory depression. Evidence regarding misuse and diversion of gabapentinoids has grown in recent years 8 — The first description of their misuse and abuse were published in Prevalence of misuse and abuse in the general population is an estimated 2. In a systematic review aimed to evaluate the abuse liability of gabapentin and pregabalin, the authors found that pregabalin had a greater potential for addiction than gabapentin based on the magnitude of behavioral dependence symptoms, transitions from prescription to self-administration, and the durability of the self-administrations 8. Current research suggests that the addictive potential of gabapentinoids is primarily a concern among patients with other substance use disorders, especially opioid use disorder 8. The reasons that motivate gabapentinoid misuse and abuse are not clearly described. According to a recent systematic review 13 , one of the most predictive factors associated with gabapentinoid use was the concomitant use of opioids. The neurobiological mechanism involved in the abuse liability of gabapentinoids has not been yet clearly investigated. The usual increase in the dopamine levels at the mesolimbic brain circuits has not been proved in preclinical studies 14 , Other reported effects include dissociative feeling, improved sociability, relaxation and sense of calm, and psychedelic effects 10 , On the other hand, however, there are studies indicating that gabapentin could be an useful treatment for alcohol use disorder. For instance, a recent randomized controlled trial showed efficacy of gabapentin in the treatment of alcohol use disorder, improving the alcohol withdrawal syndrome, reducing the heavy drinking days and more total abstinence in the group treated with 1, mg of gabapentin Also, in a meta-analysis of seven studies, gabapentin showed efficacy in the treatment of alcohol use disorder, reducing the number of heavy drinking days That means that it is illegal to dispense them without a signed prescription, but that they do not require safe custody in controlled drug cabinets. In Spain, Italy, Germany, and France, gabapentin and pregabalin are available both only under a medical prescription. Alternatively, in the USA, the Drug Enforcement Administration DEA classifies pregabalin as a Schedule V controlled substance, or the lowest abuse potential among controlled substances, and gabapentin as a non-controlled substance The aim of this study is to determine the prevalence of prescription gabapentinoids non-medical use and associated demographics in five European countries France, Germany, Italy, Spain, and the United Kingdom and to evaluate the main factors related with its misuse in Spain. The methodology and the validity of this program is explained in its validation study 21 , Recruitment and data collection are delivered to country-based members through a global survey panel company, in the native language of the country where the survey is undertaken and in English. The surveys were available during the following timeframes: In France: from December 13 to , January, 7: in Germany: from December 12 to , January, 16; in Italy: , from December 14 to December 26; in Spain: From December 12 to , January, 4; and in UK: , from September 28 to December 1. Calibration weights were applied to the survey population to be representative of the distribution of the adult population of each of the countries included in the study based on geographic region, age, sex, limitations in daily activities, and smoking status Data used in this analysis is from the surveys launched in the second half of 17Q4. The prevalence of prescription or NMU in the last 12 months was estimated by gender and age. In the last quarter of , approximately 63, French panelists were invited to participate in the survey. Of the 16, who initiated the survey, the inclusion and exclusion criteria below were applied and a total of 10, respondents were included in the analysis 5, Of the 21, who initiated the survey, 15, completed it and fulfilled the inclusion criteria 7, In Italy, 41, Italian panelists were invited to participate in the survey. Of the 12, who initiated the survey, the inclusion and exclusion criteria below were applied and 10, surveys were included 5, females In Spain, 26, panelists were invited to participate in the survey. Of the 15, who initiated the survey, the inclusion and exclusion criteria below were applied Figure 1. Finally, 10, people completed the survey 5, In the United Kingdom, there were , panelists invited to participate in the survey, of which 13, initiated the survey and 10, were included in the analysis 5, Rates based on the weighted estimated number of adults who reported NMU of each drug class in the last 90 days per , adult population. Rates are based on the weighted estimated number of adults who reported NMU of each drug class in the last 90 days per , standard units sold. NMU was evenly distributed between genders except in Spain which showed a male predominance Table 2. Those who non-medically use GABA analogs were estimated to have higher incidence of lifetime chronic pain, lifetime illicit drug use, and previous substance abuse therapy Table 2. Approximately 26, Spanish panelists were invited to participate in the survey. The main characteristics unweighted and weighted of the respondents are described in Table 3. The responses are weighted to represent the population above 15 years old in Spain by region, gender and age. A total of 1, From the total Spanish sample, 4. Out of them, 84 The others respondents were not sure 40 9. The main reasons for non-medical use were to self-treat pain and other medical condition different from pain Table 5. Includes all survey respondents who report non-medical use of the product. Respondents who declare NMU of gabapentinoids, usually used the oral route of administration either swallowed or chewed and then swallowed. Includes all survey respondents who report each reason for non-medical use of the product. Finally, in Table 8 , is described the last purchase of gabapentin and pregabalin where respondents said that they have obtained the substances from a dealer of bought in internet. The main finding of this study is that it confirms the potential abuse liability and then non-medical use of the gabapentinoids gabapentin and pregabalin. When comparing the five European countries, those who non-medically use gabapentinoids were estimated to have a higher likelihood of chronic pain, use of illicit substances, and history of substance abuse treatment compared to the general population. These results are in concordance with country surveys, reviews and metanalyses published previously 8 , 23 , There are differences in the rate per , people among the five countries, with Germany and UK the countries having a higher rate compared to France, Italy and Spain. Reasons for these differences could be related to the availability of other sedative type substances in those countries. We can hypothesize that some reasons for using cannabis and gabapentinoids could be similar: to treat pain and anxiety symptoms; in countries with higher availability of cannabinoids and opioids, subjects could prefer them to gabapentinoids. Also, in some countries, gabapentinoids might replace partially benzodiazepines; in Spain, a general population survey performed every 2 years, showed data on life-time NMU of benzodiazepines about 3. Some studies have tried to analyze the possible usefulness of pregabalin and gabapentin in the treatment of benzodiazepine use disorder, but there are no clear results regarding this 27 , When evaluating the rates by drug, as described before, pregabalin has more endorsements than gabapentin, for example, in a recent paper describing data from addictovigilance monitoring for gabapentinoids Some publications have described a higher abuse liability for pregabalin compared to gabapentin. One of the explanations of this difference could be the higher prevalence of euphoria in pregabalin compared to gabapentin. The theory of people taking pregabalin to experience euphoria and to get high it is not completely explained by our results, as the majority of the respondents used pregabalin as self-treatment. The differences between the two substances could also be explained by the different pharmacokinetic characteristics of both molecules; pregabalin has more rapid absorption than gabapentin; also, the peak plasma concentration is more rapidly achieved with pregabalin 1 h compared to 4—5 h and has a longer half-life 7. A risk for NMU that should not be neglected. The main reason for non-medical use was in both medications for self-treat any pain, followed to treat other medical conditions; few respondents used them to get high or to come down; also, there were a percentage of people using them to prevent withdrawal symptoms. Another article, based on data of pharmavigilance 24 , found that the use of pregabalin was not only related to the objective to get high, but also, to prevent withdrawal symptoms, as a substitute of other substances and to potentiate the effect of other drugs mainly benzodiazepines and opioids. In our sample, the inhaled and intravenous route were mainly reported for those who use pregabalin and gabapentin to prevent withdrawal syndrome, to come down and to get high. It is important to consider the possibility of using the intravenous route, and asking patients about it to prevent the transmission of blood borne infections Hepatitis B and C, and HIV. Another aspect to take into account may be the polymedication risk. This combination could increase the risk for overdose death Otherwise, the usefulness of the combination of pregabalin and opioids for the treatment of some kind of pain is not clear, as some researchers have described that pregabalin plus opioids was associated with more pain severity and higher oral doses of opioids; furthermore, pregabalin use was not associated with improvements on mental health symptoms When prescribing these medications it is important to be aware and monitor for signs of misuse and overdosification, mainly in patients with risk factors for NMU previous history of substance use disorder and chronic pain. It is important to remark that, although NMU of gabapentinoids is more frequent in patients with previous substance use disorder, there are described cases of a primary abuse in people without any of the known risk factors 24 , for this reason, it is important to monitor for signs of NMU in all patients in treatment with gabapentinoids. The detection of NMU could be complicated as these medications are not detected in routine toxicology urine controls. Furthermore, prescribers should be aware of the risk of NMU, when patients request for specific drugs of higher doses, when they obtain medications from different sources doctor shopping , when the medications are lost or stolen frequently or they ask for new prescriptions too early 1. The NMURx survey methodology is useful to identify under-documented use and misuse of medication and can detect changes in trends of substance use and misuse; also, it permits to make comparisons among different countries. The large sample size and post-stratification weighting applied creates estimates that are representative of general populations. However, there are some limitations related to online surveys, in first place the reliance of participants to provide honest responses; also, another limitation of the study is that respondents who have acquired a gabapentinoid product from a family member, friend, or dealer may not be aware whether it was initially obtained with a prescription or from another source. However, these limitations will apply to all surveys so still allow for comparison across countries. In conclusion, in spite of the risk of NMU, gabapentinoids are useful medications in the treatment of neuropathic pain, generalized anxiety disorder, and some forms of epilepsy. Professionals prescribing these medications should be aware and actively search for signs of misuse and diversion. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. MG and RD were responsible for the project concept and study design. All authors have read and approved the final submitted manuscript. During the last 3 years he participated in clinical trials financed by the pharmaceutical industry. The remaining authors declare that conflicts of interest had no role in the design of the study, data collection, analyses, and interpretation, in the writing of the manuscript, or in the decision to publish the results. The RADARS System is supported by subscriptions from pharmaceutical manufacturers, government, and non-government agencies for surveillance, research, and reporting services. Authors were employed by Denver Health and Hospital Authority during this work. Denver Health retains exclusive ownership of all data, databases and systems. No subscriber participated in the conception, analysis, drafting, or review of this manuscript. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Front Psychiatry. Find articles by Francina Fonseca. Find articles by William Lenahan. Find articles by Richard C Dart. Find articles by Esther Papaseit. Find articles by Paul I Dargan. Find articles by David M Wood. Find articles by Marilena Guareschi. Icro Maremmani 10 Vincent P. Find articles by Icro Maremmani. Find articles by Marc Auriacombe. Find articles by Norbert Scherbaum. Find articles by Marta Torrens. Received Mar 4; Accepted Mar 29; Collection date Open in a new tab. Respondents may check multiple options, percentages may not sum to Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Previous substance abuse treatment. Student within the last 3 months. A member or former member of the armed forces. Currently a healthcare professional. Pregnancy status b. Gestation c months. Gabapentin e. Pregabalin e. N: 45 Mean STD : 5. N: 12 Mean STD : N: 45 Mean STD : N: 52 Mean STD : 5. N: 16 Mean STD : N: 52 Mean STD : ,

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In just four years, heroin addiction has risen in Italy largely due to its cheap price tag. However, these recent revelations by the EMCDDA parallel numbers released in May in the United States, where a recent study revealed that heroin use has increased fivefold in the last decade. Today, the majority of heroin users prefer to snort or smoke the drug, preferably in combination with other durgs such as cocaine or alcohol. The drug of choice varies, but there seems to be something for everyone. For the desperate addict there is heroin at 5 euros a gram, while career professionals can add various amphetamines to the mix. With the price of the drug getting cheaper, the age at which somebody first experiments with drugs is getting younger too - average 13 years old. This explains why first-timers are given their first hit for free: it creates an ideal environment for drug dealers to operate lucrative businesses if they can hook someone early on and turn them into loyal customers overthe next 20 to 30 years. For supply to meet demand, the map of heroin distribution has been redrawn in Italy. Milan, with its easy access to all of northern Italy by train, has become a hotbed for heroin. Rogoredo Station and Parco delle Groane are prime points of sale in the Italian capital. Raids are carried out periodically in these locations, but addicts determinded to score and dealers determined to sell, return to their territories despite the possibility of being caught. Meanwhile, 34 percent of people behind bars are put away on drug-related charges. Elsewhere, heroin 52 percent is reported by the EMCDDA as the main substance used by the majority of clients entering treatment in Italy. He added that most drug addicts relapse once they leave the facilities. One way to assure recovery, he suggested, is by doing sports and volunteering with mentors that can help them cope and adjust to life again outside the facilities, especially at night and on weekends, when the temptation is highest. Il Quotidiano Abbonati. Menu Cerca Notifiche. La guida allo shopping del Gruppo Gedi i Consigli. Ogni volta che viene fatto un acquisto attraverso uno dei link presenti nel testo, Consigli.

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