Risk Prescriptions of Strong Opioids in the Treatment of Chronic Non-Cancer Pain by Primary Care Physicians in Catalonia: Opicat Padris Project

The prescription of strong opioids (SO) for chronic non-cancer pain (CNCP) is steadily increasing. This entails a high risk of adverse effects, a risk that increases with the concomitant prescription of SO with central nervous system depressant drugs and with the use of SO for non-recommended indications. In order to examine this concomitant risk prescription, we designed a descriptive, longitudinal, retrospective population-based study. Patients aged >= 15 years with a continued SO prescription for >= 3 months during 2013-2017 for CNCP were included. Of these, patients who had received concomitant prescriptions of SO and risk drugs (gabapentinoids, benzodiazepines and antidepressants) and those who had received immediate-release fentanyl (IRF) were selected. The study included 22,691 patients; 20,354 (89.7%) patients received concomitant risk prescriptions. Men and subjects with a higher socioeconomic status received fewer concomitant risk prescriptions. Benzodiazepines or Z-drugs were prescribed concomitantly with SO in 15,883 (70%) patients, antidepressants in 14,932 (65%) and gabapentinoids in 11,267 (49%), while 483 (21.32%) patients received IRF (2266 prescriptions in total) without a baseline SO. In conclusion, our study shows that a high percentage of patients prescribed SO for CNCP received concomitant prescriptions with known risks, as well as IRF for unauthorized indications

Trends in the Prescription of Strong Opioids for Chronic Non-Cancer Pain in Primary Care in Catalonia: Opicat-Padris-Project

In chronic non-cancer pain (CNCP), evidence of the effectiveness of strong opioids (SO) is very limited. Despite this, their use is increasingly common. To examine SO prescriptions, we designed a descriptive, longitudinal, retrospective population-based study, including patients aged >= 15 years prescribed SO for >= 3 months continuously in 2013-2017 for CNCP in primary care in Catalonia. Of the 22,691 patients included, 17,509 (77.2%) were women, 10,585 (46.6%) were aged >80 years, and most had incomes of <euro18,000 per year. The most common diagnoses were musculoskeletal diseases and psychiatric disorders. There was a predominance of transdermal fentanyl in the defined daily dose (DDD) per thousand inhabitants/day, with the greatest increase for tapentadol (312% increase). There was an increase of 66.89% in total DDD per thousand inhabitants/day for SO between 2013 (0.737) and 2017 (1.230). The mean daily oral morphine equivalent dose/day dispensed for all drugs was 83.09 mg. Transdermal fentanyl and immediate transmucosal release were the largest cost components. In conclusion, there was a sustained increase in the prescription of SO for CNCP, at high doses, and in mainly elderly patients, predominantly low-income women. The new SO are displacing other drugs

There is no age limit for methadone: a retrospective cohort study

BACKGROUND: Data from the US indicates that methadone-maintained populations are aging, with an increase of patients aged 50 or older. Data from European methadone populations is sparse. This retrospective cohort study sought to evaluate the age trends and related developments in the methadone population of Basel-City, Switzerland. METHODS: The study included methadone patients between April 1, 1995 and March 31, 2003. Anonymized data was taken from the methadone register of Basel-City. For analysis of age distributions, patient samples were split into four age categories from '20-29 years' to '50 years and over'. Cross-sectional comparisons were performed using patient samples of 1996 and 2003. RESULTS: Analysis showed a significant increase in older patients between 1996 and 2003 (p < 0.001). During that period, the percentage of patients aged 50 and over rose almost tenfold, while the proportion of patients aged under 30 dropped significantly from 52.8% to 12.3%. The average methadone dose (p < 0.001) and the 1-year retention rate (p < 0.001) also increased significantly. CONCLUSIONS: Findings point to clear trends in aging of methadone patients in Basel-City which are comparable, although less pronounced, to developments among US methadone populations. Many unanswered questions on medical, psychosocial and health economic consequences remain as the needs of older patients have not yet been evaluated extensively. However, older methadone patients, just as any other patients, should be accorded treatment appropriate to their medical condition and needs. Particular attention should be paid to adequate solutions for persons in need of care

One size does not fit all-evolution of opioid agonist treatment in a naturalistic setting over 23 years

Background and aims Opioid agonist treatment (OAT) is currently the most effective treatment for people with opioid dependence. In most countries, however, access to the whole range of effective medications is restricted. This study aims to model the distribution of different OAT medications within a naturalistic and relatively unrestricted treatment setting (Zurich, Switzerland) over time, and to identify patient characteristics associated with each medication. Methods We used generalized estimating equation analysis with data from the OAT register of Zurich and the Swiss register for heroin‐assisted treatment (HAT) to model and forecast the annual proportion of opioids applying exponential distributions until 2018 and patient characteristics between 1992 and 2015. Results Data from 11 895 patients were included in the analysis. Methadone remains the mainstay of OAT, being prescribed to two‐thirds of patients. Following its approval, the proportion of HAT increased rapidly and is now constant at 12.16% [95% confidence interval (CI) = 11.15–13.17]. The initial increase of proportions of buprenorphine or slow‐release oral morphine (SROM) following their approval for OAT was slower. While in 2014 both medications had a proportion of 10.2% and 10.3%, respectively, our model predicts a further increase of SROM to 19.9% in 2018, with a ceiling level of 25.19% (21.40–28.98%) thereafter. SROM patients display characteristics similar to those treated with methadone; buprenorphine patients show the highest social integration; and HAT patients are the most homogeneous group, with highest mean age, most widespread injecting experience and lowest social integration. Conclusions Based on data from Zurich, Switzerland from 1992 to 2015, there is no evidence for an excessive demand for a single medication in a naturalistic and liberal opioid agonist treatment setting. Rather, the specific patient characteristics associated with each medication underline the need for diversified treatment options for opioid dependence

Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence

Kenneth M D&uuml;rsteler,1,2 Eva-Maria Berger,1 Johannes Strasser,1 Carlo Caflisch,2 Jochen Mutschler,2 Marcus Herdener,2 Marc Vogel1 1Center for Addictive Disorders, Psychiatric University Clinics Basel, Basel, Switzerland; 2Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland Background: Cocaine use continues to be a public health problem, yet there is no proven effective pharmacotherapy for cocaine dependence. A promising approach to treating cocaine dependence may be agonist-replacement therapy, which is already used effectively in the treatment of opioid and tobacco dependence. The replacement approach for cocaine dependence posits that administration of a long-acting stimulant medication should normalize the neurochemical and behavioral perturbations resulting from chronic cocaine use. One potential medication to be substituted for cocaine is methylphenidate (MPH), as this stimulant possesses pharmacobehavioral properties similar to those of cocaine. Aim: To provide a qualitative review addressing the rationale for the use of MPH as a cocaine substitute and its clinical potential in the treatment of cocaine dependence. Methods: We searched MEDLINE for clinical studies using MPH in patients with cocaine abuse/dependence and screened the bibliographies of the articles found for pertinent literature. Results: MPH, like cocaine, increases synaptic dopamine by inhibiting dopamine reuptake. The discriminative properties, reinforcing potential, and subjective effects of MPH and cocaine are almost identical and, importantly, MPH has been found to substitute for cocaine in animals and human volunteers under laboratory conditions. When taken orally in therapeutic doses, its abuse liability, however, appears low, which is especially true for extended-release MPH preparations. Though there are promising data in the literature, mainly from case reports and open-label studies, the results of randomized controlled trials have been disappointing so far and do not corroborate the use of MPH as a substitute for cocaine dependence in patients without attention deficit hyperactivity disorder. Conclusion: Clinical studies evaluating MPH substitution for cocaine dependence have provided inconsistent findings. However, the negative findings may be explained by specific study characteristics, among them dosing, duration of treatment, or sample size. This needs to be considered when discussing the potential of MPH as replacement therapy for cocaine dependence. Finally, based on the results, we suggest possible directions for future research. Keywords: agonist replacement, dependence, substitutio

Assessment of alcohol use among methadone maintenance patients by direct ethanol metabolites and self-reports

BACKGROUND: Heavy alcohol consumption may accelerate the progression of hepatitis C (HCV)-related liver disease and/or limit efforts at antiviral treatment. As most of the patients in methadone maintenance treatment (MMT) suffer from hepatitis C infection, this study was conducted to identify the alcohol intake among these patients at a Swiss Psychiatric University Clinic by self-reports and direct ethanol metabolites as biomarkers of ethanol consumption. PATIENTS AND METHODS: A convenience sample of 40 MMT patients (15 women, 25 men; median age 39 years) of the total 124 patients was asked and consented to participate in this study. This sample was not different in age, gender distribution, and rate of hepatitis C infection from the total sample. The Alcohol Use Disorders Identification Test (AUDIT) and self-reported ethanol intake during the previous 7 days were assessed. In addition, ethyl glucuronide (EtG) in urine, and fatty acid ethyl esters (FAEEs) and EtG in hair were determined using LC-MS/MS and gas chromatograph/mass spectrometer. The limit of quantitation for UEtG, HEtG, and FAEEs were 0.1 mg/l, 2.3 pg/mg, and 0.1 ng/mg, respectively. RESULTS: Fourteen participants reported abstinence from alcohol for the previous 7 days. AUDIT scores were > or =8 in 15 male and >5 in 5 female participants. Direct ethanol metabolites were as follows (median, min, max, standard deviation): UEtG (19 positives; 9.91, 1.38 to 251, 62.39 mg/l); the values of HEtG were 17.65, 0 to 513, 105.62 pg/mg [in 2 cases no material, 8 abstinent (up to 7 pg/mg), 15 social drinkers (up to 50 g per day), and 15 excessive users (>50/60 g/d)]. For the 13 cases, where enough material for additional determination of HFAEEs was available, the values were 0.32, 0 to 1.32, 0.44 ng/mg. Among the 30 HEtG-positive participants, 20 had not reported the corresponding ethanol intake using question 1 (frequency) and 2 (quantity) of the AUDIT. Of the 14 participants reporting no alcohol intake during the previous 7 days, 4 were UEtG-positive. HEtG and AUDIT correlated significantly (r = 0.622, p < 0.0001), but this was not the case for UEtG and self-reported ethanol intake during the previous 7 days. CONCLUSION: (1) HEtG identified 20 cases of daily ethanol intake of more than 20 g, that would have been missed by the sole use of question 1 (frequency) and 2 (quantity) of the AUDIT. (2) Using the total score of the AUDIT, HEtG confirmed 10 more cases positive for alcohol intake. (3) Episodic heavy drinking is with 22.5% more frequent than in general population, and (4) of the 14 participants who reported no alcohol intake during the previous 7 days, 4 were UEtG positive. Improved detection of alcohol consumption, which is hazardous or harmful in the context of HCV and opiate dependence, would allow for earlier intervention in this population which is at particular risk of liver disease and fatal respiratory-depressed overdose. The combined use of self-reports and direct ethanol metabolites seems promising

Randomisierte kontrollierte Studie zur Einsatzmöglichkeit von Methylphenidat und kognitiv-behavioraler Gruppenpsychotherapie bei Kokain konsumierenden Patienten in opioidgestützter Behandlung

Seit Jahren ist der Kokainkonsum unter Opiatabhängigen verbreitet und stellt auch in opioidgestützten Behandlungen ein Problem dar. Bislang gibt es keine effektive Pharmakotherapie. Eine vielversprechende Behandlungsform ist die kognitiv-behaviorale Therapie. Die vorliegende randomisierte kontrollierte Pilotstudie mit vier Armen hat bei 62 kokainabhängigen Personen aus einer heroingestützten Behandlung placebokontrolliert und doppelblind die Einsatzmöglichkeit von Methylphenidat (MP) mit und ohne kognitiv-behaviorale Gruppentherapie (CBT) untersucht. Primäre Zielvariablen waren das Verbleiben in der medikamentösen Behandlung, der Kokainkonsum und unerwünschte Ereignisse. Die Studie wurde in zwei Zentren durchgeführt. Nach einer umfassenden Basiserhebung wurden die Versuchspersonen über zwölf Wochen entsprechend der Zufallszuteilung behandelt (MP oder Placebo, jeweils mit oder ohne CBT). Die Studienmedikation (30 mg MP oder Placebo) wurde zweimal täglich unter Aufsicht eingenommen. Die manualisierten Gruppentherapien wurden einmal pro Woche durchgeführt, die Teilnahme war freiwillig. Die Zielvariablen wurden regelmässig mit Befragungen und Urinproben erfasst. Die Datenanalyse erfolgte nach dem „Intent-to-treat-Prinzip“, wobei neben herkömmlichen statistischen Verfahren auch Multilevel-Modelle (GEE) gerechnet wurden. Von der Stichprobe verblieben 71% über zwölf Wochen in der Studie. Die Medikation wurde insgesamt gut toleriert. Die Studie lieferte keine Hinweise dafür, dass MP und/oder CBT in diesem Kollektiv den Kokainkonsum reduzieren. Die CBT besitzt für die Zukunft aber dennoch Potenzial