Pregabalin use in forensic hospitals and prisons in German speaking countries-a survey study of physicians.

Background: Pregabalin is a gamma-aminobutyric acid (GABA) analog that was approved in the EU in 2004 for the treatment of neuropathic pain, generalized anxiety disorder and epilepsy. Since its introduction, pregabalin abuse and misuse has increased significantly. In Switzerland, clinical reports suggest that pregabalin misuse is common among patients in forensic hospitals and prisons. However, data on pregabalin use is scarce, especially in these settings. Therefore, we conducted a study to explore patterns of pregabalin use among prison and forensic patients. Methods: We used a questionnaire to survey physicians working in prison and forensic medicine in German-speaking countries. A total of 131 responses were received. Results: According to the physicians' subjective assessment, 82.5% of them had observed a recent increase in pregabalin use by their patients and 89.1% of them reported that their patients requested pregabalin without a clear medical indication. Patients misusing pregabalin in combination with other illicit substances were observed by 93.3% of the physicians surveyed. According to 73.5% of the physicians surveyed, they had already encountered patients on pregabalin doses of more than 600 mg/day (the maximum recommended daily dose); the highest dose reported was 4,200 mg/day. According to 85.0% of physicians surveyed, they have observed patients experiencing withdrawal symptoms from pregabalin, with the most commonly reported symptoms being displeasure and high aggression. Regarding the nationality of pregabalin-misusing patients, 58.3% of the interviewed physicians reported to be rather in contact with foreign patients, mainly from Northwest Africa (Maghreb). Only 45.0% of the surveyed physicians prescribe pregabalin. Among patients who developed behavioral problems while taking pregabalin, none of the physicians (0.0%) showed a tendency to continue pregabalin at the same dose; all respondents chose to reduce/substitute/discontinue. Conclusion: Our study has provided confirmatory evidence that the use of pregabalin presents a significant issue in forensic and prison medicine across German-speaking countries. Prescribing pregabalin in this field can compound use disorder problems and exacerbate challenges in daily life for those in forensic institutions or prisons. It is necessary that all physicians who prescribe pregabalin are clearly informed about the management (including the risks) of this drug.

Predictors of weight loss in participants with obesity following bariatric surgery - A prospective longitudinal fMRI study.

Prevalence rates of overweight and obesity are increasing worldwide and are amongst the leading causes of death. Participants with obesity also suffer from poorer mental health with a concomitant reduced quality of life. Bariatric surgery outperforms other existing weight optimization approaches. However, hitherto, it was not possible to identify factors predicting weight loss following surgery. Therefore, we aimed at investigating neural and behavioral predictors of weight loss, as well as the neurological underpinnings of food cue-induced craving before and after bariatric surgery. The total sample consisted of 26 participants with obesity (17 females and 9 males, mean age 41 ± 12 years, mean BMI 46 ± 6 kg/m2, 21 received Roux-en-Y gastric bypass and 5 sleeve gastrectomy). Participants with obesity were prospectively assessed using functional magnetic resonance imaging two weeks before, as well as eight and 24 weeks after surgery. Imaging data were available for 11 individuals; 10 received Roux-en-Y gastric bypass and one sleeve gastrectomy. Subjective cue-induced food craving correlated positively with brain activation in the amygdala, the parahippocampal gyrus, and hippocampus, and negatively with brain activation in frontal brain regions. In the total sample (N = 26), perceived feeling of hunger and YFAS sum score explained 50.6% of the variance (R2 = 0.506, F(1,23) = 10.759, p < 0.001) and in the imaging sample, cue-induced food craving at baseline before surgery explained 49.6% of the variance (R2 = 0.496, F(1,23) = 7.862, p = 0.023) of % total weight loss (%TWL). In other words, with respect to %TWL, bariatric surgery was most efficient in candidates characterized by high cue-induced food craving, high-perceived feeling of hunger and a low YFAS sum score.

BDNF influences neural cue-reactivity to food stimuli and food craving in obesity.

There is increasing evidence that brain-derived neurotrophic factor (BDNF) impacts on the development of obesity. We are the first to test the hypothesis that BDNF levels might be associated with neural reactivity to food cues in patients suffering from obesity and healthy controls. We assessed visual food cue-induced neural response in 19 obese patients and 20 matched controls using functional magnetic resonance imaging and analyzed the associations between BDNF levels, food cue-reactivity and food craving. Whole-brain analysis in both groups revealed that food cues elicited higher neural activation in clusters of mesolimbic brain areas including the insula (food > neutral). Patients suffering from obesity showed a significant positive correlation between plasma BDNF levels and visual food cue-reactivity in the bilateral insulae. In addition, patients suffering from obesity with positive food cue-induced insula activation also reported significantly higher food craving than those with low cue-reactivity-an effect that was absent in normal weight participants. The present findings implicate that BDNF levels in patients suffering from obesity might be involved in food craving and obesity in humans. This highlights the importance to consider BDNF pathways when investigating obesity and obesity treatment.

Reliability of neural food cue-reactivity in participants with obesity undergoing bariatric surgery: a 26-week longitudinal fMRI study.

Obesity is highly prevalent worldwide and results in a high disease burden. The efforts to monitor and predict treatment outcome in participants with obesity using functional magnetic resonance imaging (fMRI) depends on the reliability of the investigated task-fMRI brain activation. To date, no study has investigated whole-brain reliability of neural food cue-reactivity. To close this gap, we analyzed the longitudinal reliability of an established food cue-reactivity task. Longitudinal reliability of neural food-cue-induced brain activation and subjective food craving ratings over three fMRI sessions (T0: 2 weeks before surgery, T1: 8 weeks and T2: 24 weeks after surgery) were investigated in N = 11 participants with obesity. We computed an array of established reliability estimates, including the intraclass correlation (ICC), the Dice and Jaccard coefficients and similarity of brain activation maps. The data indicated good reliability (ICC > 0.6) of subjective food craving ratings over 26 weeks and excellent reliability (ICC > 0.75) of brain activation signals for the contrast of interest (food > neutral) in the caudate, putamen, thalamus, middle cingulum, inferior, middle and superior occipital gyri, and middle and superior temporal gyri and cunei. Using similarity estimates, it was possible to re-identify individuals based on their neural activation maps (73%) with a fading degree of accuracy, when comparing fMRI sessions further apart. The results show excellent reliability of task-fMRI neural brain activation in several brain regions. Current data suggest that fMRI-based measures might indeed be suitable to monitor and predict treatment outcome in participants with obesity undergoing bariatric surgery.

Telecommunications Network Measurements of Online Gambling Behavior in Switzerland: A Feasibility Study.

BACKGROUND: Methodological shortcomings of gambling studies relying on self-report or on data sets derived from gambling operators tend to result in biased conclusions. The aim of this study was to analyze online gambling behavior using a novel network database approach. METHODS: From October 13 to October 26, 2014, telecommunications network data from a major telecommunications provider in Switzerland were analyzed. Netflows between mobile devices and a poker operator were quantified to measure the gambling duration and session number. RESULTS: Time spent gambling during night and working hours was compared between devices with longest (red group), intermediate (orange group), and shortest gambling time (green group). Online gambling behavior differed depending on overall gambling time, F (2, 3,143). Night and working hours gambling was the highest in the red group (53%), compared to the orange (50.1%) and the green groups (41.5%). Post hoc analyses indicated significant differences between the orange and green groups (p < 0.05). No differences were observed between the red and orange groups (p = 0.850), and the red and green groups (p = 0.053). CONCLUSIONS: On mobile devices, distinct gambling patterns were observed depending on the overall gambling time. This methodology could also be used to investigate online gaming, social media use, and online pornography.

Association of plasma calcium concentrations with alcohol craving: New data on potential pathways.

Recently, calcium was suggested to be the active moiety of acamprosate. We examined plasma calcium concentrations in association with severity of alcohol dependence and its interaction with regulating pathways and alcohol craving in alcohol-dependent patients. 47 inpatient alcohol-dependent patients undergoing detoxification treatment underwent laboratory testing, including calcium, sodium, liver enzymes as well as serum concentrations of calcitonin, parathyroid hormone and vitamin D. The psychometric dimension of craving was analyzed with the Obsessive Compulsive Drinking Scale (OCDS). The severity of withdrawal was measured with the Alcohol Dependence Scale (ADS) and with the Alcohol Dependence Scale for high-risk sample (ADS-HR). The main findings of our investigation are: a) a negative correlation of plasma calcium concentrations with alcohol craving in different dimensions of the OCDS; b) a negative correlation of plasma calcium concentrations with breath alcohol concentration; c) lowered calcitonin concentration in the high-risk sample of alcoholics; d) lowered plasma vitamin D concentrations in all alcoholic subjects. Our study adds further support for lowered plasma calcium concentrations in patients with high alcohol intake and especially in patients with increased craving as a risk factor for relapse. Lowered calcitonin concentrations in the high-risk sample and lowered vitamin D concentrations may mediate these effects. Calcium supplementation could be a useful intervention for decreasing craving and relapse in alcohol-dependent subjects.

The association of pineal gland volume and body mass in obese and normal weight individuals: a pilot study.

BACKGROUND: In obese individuals impaired sleep and neuroendocrine alterations such as melatonin deficits are associated with circadian rhythm disruption, altered circadian clock gene expression, and bright light at night. While the relation of pineal gland volume (PGV) and melatonin levels has recently been documented in humans, surprisingly little is known about the possible interference of the PGV and the pathophysiology of obesity in humans. SUBJECTS AND METHODS: We therefore compared the PGV of obese with non-obese individuals; both groups were matched by age and gender. Volumetric analyses were performed on the basis of 3 Tesla high resolution Magnetic Resonance Imaging (MRI). RESULTS: We found, that the PGV was significantly smaller in obese individuals than in lean controls (P=0.036). Moreover, PGV and waist-hip ratio showed a significant negative association in controls (P=0.018, rs=-0.602) whereas no association of both variables was found in obese individuals (P=0.856, rs=-0.051). CONCLUSIONS: Thus, the current pilot investigation suggests that pineal gland function, reflected by PGV might be involved in the energy homeostasis and pathophysiological mechanisms that contribute to the development and the maintenance of obesity in humans. Moreover, our data supports the notion that the replacement of melatonin deficits might be a novel strategy in the treatment of obesity.

["Food addiction" as a possible risk factor for obesity]. / «Ess-Sucht¼ als eine mögliche Ursache der Adipositas.

The prevalence rates of overweight and obesity are, internationally as well as in Switzerland, increasing in recent years. The neurobiology tries to explore an improved understanding of the central nervous causes of obesity. Findings from addiction research seem very useful because there are certain similarities between addiction and obesity in terms of neurobiological causes. An improved understanding of the disease of obesity could help to develop more effective therapies for obese patients in the future. Further research, e. g. in the field of stress regulation, is thus urgently needed.

Treatment of cocaine craving with as-needed nalmefene, a partial κ opioid receptor agonist: first clinical experience.

The treatment of cocaine dependence is difficult as no approved pharmacotherapy is available as yet. However, in preclinical and clinical trials, a variety of compounds were tested for suitability as inhibitors of craving for and relapse into the use of cocaine, among these antidepressants, antiepileptics, dopamine agonists, disulfiram, and naltrexone. Nalmefene, a structural derivative of naltrexone, shares with its parent compound approval (granted by the European Medical Agency in 2013) as a medication for the treatment of alcohol addiction in the European Union. It differs from naltrexone by a higher affinity for the δ opioid-receptors and a partial agonistic affinity to the κ opioid-receptors. It should be noted that patients addicted to cocaine show a considerable increase in κ receptors in the nucleus accumbens. This report describes the case of an abstinent cocaine-addicted patient regularly afflicted with cravings for cocaine. The patient took as-needed nalmefene for 5 months whenever she developed a craving for cocaine. For most of these interventions, the patient reported an abatement of craving and could avoid relapsing into cocaine consumption. This effect may be accounted for by nalmefene acting, other than naltrexone, as a partial agonist of the κ opioid-receptors. Therefore, nalmefene might be a promising new option in the pharmacological repertoire for the treatment of cocaine addiction.

Oleoylethanolamide and human neural responses to food stimuli in obesity.

IMPORTANCE: Obesity has emerged as a leading health threat but its biological basis remains insufficiently known, hampering the search for novel treatments. Here, we study oleoylethanolamide, a naturally occurring lipid that has been clearly implicated in weight regulation in animals. However, its role for weight regulation and obesity in humans is still unclear. OBJECTIVE: To investigate associations between plasma oleoylethanolamide levels and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) and functional magnetic resonance imaging response to food stimuli in obese patients and matched control participants. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of 21 obese patients and 24 matched control participants. Obesity was defined as having a BMI of at least 30. The mean age of participants was 40.8 years and BMIs ranged from 18.2 to 47.5. MAIN OUTCOMES AND MEASURES: Interactions between plasma oleoylethanolamide levels and obesity on BMI and functional magnetic resonance imaging response to food stimuli. RESULTS: Associations between oleoylethanolamide and BMI differed significantly depending on whether individuals were obese or not (P = .02). In obese individuals, oleoylethanolamide showed a trend toward a positive correlation with BMI (P = .06, ρ = 0.42), while this relationship was inverse for nonobese control participants (P = .07, ρ = -0.34). Similarly, we found significant interactions between oleoylethanolamide levels and obesity on food-related brain activation in cortical areas associated with reward processing and interoceptive signaling (P = .009). Specifically, nonobese individuals with higher oleoylethanolamide levels had higher insular brain activity (P < .001, ρ = 0.70); again, the relationship trended to be inverse for obese patients (P = .11, ρ = -0.36). These effects were not associated with plasma levels of leptin and anandamide, suggesting an independent role of oleoylethanolamide in hunger-associated interoceptive signaling. Analysis of food craving during the functional magnetic resonance imaging task suggested that the identified brain areas may be involved in suppressing food-liking reactions in nonobese individuals. CONCLUSIONS AND RELEVANCE: This study suggests that oleoylethanolamide-mediated signaling plays an important role for hedonic regulation of food craving and obesity in humans and thus may be a valuable target for developing novel antiobesity drugs.

[Substance abuse in older adults]. / Sucht im Alter.

In respect of demographic change, the number of older patients with substance abuse and addiction is on the raise. In this review we present important clinical and therapeutic aspects of substance abuse and addiction in the elderly and focus on alcohol, benzodiazepines and opioids. Daily and risky alcohol consumption is common among older people. They also have an increased risk getting alcohol-related complications. For early detection, laboratory parameters and questionnaires such as the AUDIT-C are suitable. Therapeutically brief interventions have been proved successful. Also, abuse of benzodiazepines, especially low-dose addiction, is widespread among older persons, although often overlooked, and patients often do not recognize their addiction. The physician has to know the correct indication, adequate dosage and pharmacological interactions. A slow-dose reduction is recommended in case of addiction. Thanks to opioid substitution therapy, patients with an opioidaddiction can reach a higher age. Age influences the effects of the substitute, which may require an adjustment of the dosage. Treatment of elderly patients should be based on their needs and resources and is usually very effective.

Sur le plan démographique le nombre de personnes âgées abusant ou dépendant de substances est en augmentation. Dans cette revue seront présentés des aspects cliniques et thérapeutiques de l'abus et de la dépendance de substances dans cette classe de la population, en particulier en ce qui concerne l'alcool, les benzodiazépines et les opioïdes. La consommation d'alcool quotidienne est fréquente chez les personnes âgées et augmente chez elles le risque de complications. Pour la détection précoce d'un abus d'alcool des paramètres de laboratoire et des questionnaires comme le AUDIT-C sont appropriés. Des interventions thérapeutiques brèves se sont avérées efficaces. L'abus de benzodiazépines, en particulier la dépendance à ces substances à petites doses, est aussi très répandu et souvent négligé chez les personnes âgées, de telle sorte que ces dernières n'en ont pas conscience. Le médecin doit connaître l'indication correcte, le dosage adéquat et les interactions des benzodiazépines. Une réduction lente des doses est recommandée en cas de dépendance. Les patients présentant une dépendance aux opioïdes ont leur vie prolongée grâce à un traitement substitutif. L'âge influence les effets des substances substitutives, ce qui peut nécessiter des adaptations de dosage. Le traitement des personnes âgées devrait être basé sur leurs besoins et leurs ressources. Il est généralement très efficace.

Agomelatine is effective in reducing insomnia in abstinent alcohol-dependent patients.

OBJECTIVES: Sleep disorders are a widespread, persistent problem among alcohol-dependent patients and have been implicated in an increased risk for alcohol relapse. The melatonin-agonist agomelatine has been shown to improve overall sleep quality without daytime sedation. METHODS: In an off-label therapeutic setting, 9 alcohol-dependent patients with chronic sleep disorders received nightly doses of between 25 and 50 mg of agomelatine. RESULTS: After 6 weeks of agomelatine treatment, the Pittsburgh Sleep Quality Index global score for all patients had decreased significantly from a mean (SD) of 13.1 (1.7) to 7.8 (1.7) (t = 12.8; P = 0.00). CONCLUSIONS: Agomelatine is a preparation that is not prone to abuse. The current pilot investigation shows that agomelatine might offer the prospect of becoming a valuable addition to the pharmacological repertoire for the treatment of alcohol-dependence-associated insomnia.

Epigenetic alteration of the dopamine transporter gene in alcohol-dependent patients is associated with age.

Chronic alcohol abuse and dependence are associated with dysfunctional dopaminergic neurotransmission in mesocorticolimbic circuits. Genetic and environmental factors have been shown to modulate susceptibility to alcohol dependence, and both may act through epigenetic mechanisms that can modulate gene expression, e.g. DNA methylation at CpG sites. Recent studies have suggested that DNA methylation patterns may change over time. However, few data are available concerning the rate of these changes in specific genes. A recent study found that hypermethylation of the promoter of the dopamine transporter (DAT) gene was positively correlated with alcohol dependence and negatively correlated with alcohol craving. The aim of the present study was to replicate these findings in a larger sample of alcohol-dependent patients and population-based controls matched for age and sex. No difference in methylation level was observed between patients and controls, and no difference in methylation level was observed before and after alcohol withdrawal in patients. However, patients with more severe craving showed a trend towards lower DAT methylation levels (P = 0.07), which is consistent with previous findings. Furthermore, in our overall sample, DAT methylation levels increased with age. Interestingly, a separate analysis of patients suggested that this finding was mainly driven by the patient group. Although the present data do not clarify whether chronic alcohol abuse is responsible for this phenomenon or merely enhances an ageing-specific process, our findings suggest that hypermethylation in alcohol-dependent patients is a consequence, rather than a cause, of the disorder.

Hunger modulates behavioral disinhibition and attention allocation to food-associated cues in normal-weight controls.

Overeating, weight gain and obesity are considered as a major health problem in Western societies. At present, an impairment of response inhibition and a biased salience attribution to food-associated stimuli are considered as important factors associated with weight gain. However, recent findings suggest that the association between an impaired response inhibition and salience attribution and weight gain might be modulated by other factors. Thus, hunger might cause food-associated cues to be perceived as more salient and rewarding and might be associated with an impairment of response inhibition. However, at present, little is known how hunger interacts with these processes. Thus, the aim of the present study was to investigate whether hunger modulates response inhibition and attention allocation towards food-associated stimuli in normal-weight controls. A go-/nogo task with food-associated and control words and a visual dot-probe task with food-associated and control pictures were administered to 48 normal-weight participants (mean age 24.5 years, range 19-40; mean BMI 21.6, range 18.5-25.4). Hunger was assessed twofold using a self-reported measure of hunger and a measurement of the blood glucose level. Our results indicated that self-reported hunger affected behavioral response inhibition in the go-/nogo task. Thus, hungry participants committed significantly more commission errors when food-associated stimuli served as distractors compared to when control stimuli were the distractors. This effect was not observed in sated participants. In addition, we found that self-reported hunger was associated with a lower number of omission errors in response to food-associated stimuli indicating a higher salience of these stimuli. Low blood glucose level was not associated with an impairment of response inhibition. However, our results indicated that the blood glucose level was associated with an attentional bias towards food-associated cues in the visual dot probe task. In conclusion our results suggest that hunger induces an approach bias and is associated with an impairment of response inhibition when normal-weight participants are confronted with food-associated cues. These findings are important as these processes play a crucial role with regard to the control of food-intake and weight gain and are assumed to contribute to obesity. Thus, individualized treatment approaches taking into account the experience of hunger in everyday-life situations should be considered in addition to a training of response inhibition.

Pregabalin abuse among opiate addicted patients.

PURPOSE: Pregabalin is a novel GABA-analogue approved for the treatment of partial onset seizures, neuropathic pain, and general anxiety disorder. Pregabalin has been classified as a Schedule V drug with a low risk of inflicting abuse or addiction. However, some publications have indicated that pregabalin may have a potential for abuse among patients with past or current opiate addiction. Thus, we hypothesized that pregabalin might be abused by patients who were undergoing an opiate replacement therapy and never had an indication for taking pregabalin on medical grounds. METHODS: Urine specimens from 124 patients with opiate dependency syndrome and from 111 patients with other addiction disorders (alcohol, benzodiazepines, cannabis, amphetamines) were screened for pregabalin by means of a mass spectrometer analysis. RESULTS: We found 12.1 % of all urine specimens from patients with opiate addiction to be positive for pregabalin. None of the patients concerned had a medical indication for using pregabalin. In the control group, 2.7 % of the patients were tested positively for pregabalin, due to their taking it regularly for chronic pain or general anxiety. CONCLUSIONS: Our data suggest that pregabalin is liable to be abused among individuals with opiate dependency syndrome Thus, vigilance and caution are called for when patients with a past or current opiate dependency are exposed to treatment with pregabalin.

Functional social support within a medical supervised outpatient treatment program.

BACKGROUND: This study examined functional social support (FSS) and its impact on treatment outcome in alcohol-dependent outpatients treated with supervised disulfiram. METHOD: FSS was assessed cross-sectionally in 46 severe alcohol-dependent patients participating in a close-meshed biopsychosocial treatment program. The FSS was measured with the Medical Outcome Study Social Support Survey. RESULTS: We found significantly higher FSS levels in patients with a current partnership. No significant influence was found of the FSS on days until relapse and retention time. However, FSS was positively correlated with cumulative abstinence. In comparison with another patient sample, it can be shown that the patients of the close-meshed biopsychosocial treatment program seemed to perceive more FSS, presumably through the higher frequency of the outpatient treatment contacts. CONCLUSION: High FSS is associated with a current partnership and with a higher cumulative time of abstinence through close professional supervision. A better understanding of the underlying mechanisms of social relationships in alcohol-dependent patients would probably help to improve treatment outcome in the future.

Insula-specific H magnetic resonance spectroscopy reactions in heavy smokers under acute nicotine withdrawal and after oral nicotine substitution.

The aim of this study was to clarify whether addiction-specific neurometabolic reaction patterns occur in the insular cortex during acute nicotine withdrawal in tobacco smokers in comparison to nonsmokers. Fourteen male smokers and 10 male nonsmokers were included. Neurometabolites of the right and the left insular cortices were quantified by magnetic resonance spectroscopy (MRS) on a 3-Tesla scanner. Three separate MRS measurements were performed in each subject: among the smokers, the first measurement was done during normal smoking behavior, the second measurement during acute withdrawal (after 24 h of smoking abstinence), and the third shortly after administration of an oral nicotine substitute. Simultaneously, craving, withdrawal symptoms, and CO levels in exhaled air were determined during the three phases. The participants in the control group underwent the same MR protocol. In the smokers, during withdrawal, the insular cortex showed a significant increase in glutamine (Gln; p = 0.023) as well as a slight increase not reaching significance for glutamine/glutamate (Glx; p = 0.085) and a nonsignificant drop in myoinositol (mI; p = 0.381). These values tended to normalize after oral nicotine substitution treatment, even though differences were not significant: Gln (p = 0.225), Glx (p = 0.107) and mI (p = 0.810). Overall, the nonsmokers (control group) did not show any metabolic changes over all three phases (p > 0.05). In smokers, acute nicotine withdrawal produces a neurometabolic reaction pattern that is partly reversed by the administration of an oral nicotine substitute. The results are consistent with the expression of an addiction-specific neurometabolic shift in the brain and confirm the fact that the insular cortex seems to play a possible role in nicotine dependence.