Changes in Opioid Agonist Treatment Practice in Germany during the COVID-19 Pandemic: What Have Physicians Done, and What Would They Like to Keep Doing?

INTRODUCTION: Opioid agonist treatment (OAT) is the most common and most effective treatment option for persons with opioid use disorders (OUD). In Germany, the prescription of OAT medications is regulated by the Narcotic Drugs Prescription Ordinance. With the introduction of restrictions to contain the SARS-CoV-2 virus, the German OAT regulations have been amended to ensure a legal continuation of OAT for people with OUD. In this study, we aimed to examine the use of the OAT regulations in practice, the experience made by physicians prescribing OAT medications, and their perspective on OAT regulations. METHODS: Between September and December 2021, a questionnaire on the current situation and potential changes in the provision of OAT during the COVID-19 pandemic was sent out to 2,416 German physicians prescribing OAT medications. Differences between physicians with and without addiction medicine certification were analyzed. RESULTS: The response rate of physicians was 22.8%. Their average age was 57.4 (±10.1) years, and 62.3% were male. During the COVID-19 pandemic, take-home periods for stable patients have been extended by 48.2% of physicians, and 52.6% would like to maintain this prescribing practice in the future. Most physicians (71.6%) indicated that patients handled the extended take-home prescriptions predominantly responsibly. A total of 71.8% of the physicians generally did not use video consultation. A corona pandemic-related switch of the OST medication to depot buprenorphine injection did rather not occur, as 71.2% reported no patients treated with depot buprenorphine, and only 2.6% switched first-time or more patients to depot buprenorphine due to the COVID-19 pandemic. CONCLUSION: The corona situation opened up opportunities for physicians and patients and enabled change processes in OAT. Physicians had positive experiences implementing expanded take-home prescriptions for stable patients. Video contacts rarely took place, suggesting resistance to digital consultation. The number of depot buprenorphine prescriptions has not increased substantially since the pandemic's beginning and has remained at low levels. Further research is needed to assess to what extent the changes in OAT will be maintained over time and whether they will also lead to long-term benefits for OAT patients.

[Opioid agonist therapy and the German Narcotic Drugs Prescription Ordinance from the pharmacist's perspective]. / Opioidsubstitutionstherapie im Rahmen der neuen Betäubungsmittel-Verschreibungsverordnung aus Sicht von Apothekerinnen und Apothekern.

BACKGROUND: Opioid agonist therapy (OAT) has been established to be the most important therapy option for improving health and social burdens of people with opioid dependence. Pharmacies provide drug substitutes to substitution practices or outpatient clinics and administer drugs to substituted patients (medication under visual control) or supply prescriptions for unsupervised, at-home use by patients. Given the gaps in medical care, the relevance of pharmacies for the comprehensive treatment of opioid-dependent patients will become even more important in the future. The 3rd Revision of the Narcotic Drugs Prescription Ordinance (NDPO) adopted sweeping reforms to the framework of OAT in 2017. This paper examines the impact of this reform from the pharmacist's perspective. METHODS: Between November 2020 and March 2021, pharmacists in the German federal states of Hamburg, North-Rhine Westphalia, Saxony, and Bavaria were informed by their State Chambers of Pharmacists about participation in this online study. A total of 480 questionnaires were evaluated. The analysis differentiates between pharmacists who are currently involved in the substitution of opioid-dependent patients (54.2%), pharmacists who were involved in the past (21.4%), and those who have never been involved in opioid substitution (24.4%). RESULTS: Pharmacists involved in OAT have not seen any positive changes resulting from the 3rd Revision of the NDPO. According to 97.9% of the pharmacists, remuneration for administering medication under visual control should be analogous to remuneration in doctors' practices. Mixed prescriptions (prescription of take-home dose and intermediate medication under visual control) increase the administrative workload and have been rejected by a quarter of the pharmacists. Non-involved pharmacists significantly overestimated the occurrence of critical situations with substituted patients in the pharmacy. While only 2.7% of pharmacists involved in OAT reported drug emergencies, 23.1% of non-involved pharmacists expressed such concerns. 39.3% of the pharmacists felt they could be motivated to participate in OAT if they were approached directly, and 73.9% of the pharmacists who are currently involved in OAT said they could provide substitution medication under visual control to additional opioid-dependent patients. CONCLUSIONS: The 3rd Revision of the NDPO has no influence on the situation and willingness of pharmacists to be involved in OAT. However, to ensure that pharmacists continue to be actively involved in OAT and attract new substituting pharmacies, their importance for comprehensive OAT must be upgraded. This includes, and not least, the funding of pharmacists' administration of substitution drugs under visual control. In addition, knowledge about OAT, attitudes toward opioid-dependent patients, and contact anxiety could be addressed by promoting educational awareness and training.

Substitution treatment for opioid dependence with slow-release oral morphine: Retention rate, health status, and substance use after switching to morphine.

INTRODUCTION: Since April 2015, slow-release oral morphine (SROM) has been approved for opioid agonist treatment (OAT) in Germany. Experimental studies show that benefits of SROM over methadone include less heroin craving, better tolerability, and higher patient satisfaction and mental stability. The SROMOS study (Efficacy and Tolerability of Slow-Release Oral Morphine in Opioid Substitution Treatment) aims to investigate the long-term effects (effectiveness and safety) of morphine substitution under routine care in Germany. MATERIAL AND METHODS: This is a prospective, noninterventional, naturalistic, observational study. Between July 2016 and November 2017, this study recruited patients in OAT who decided to switch to SROM from 23 outpatient addiction treatment centers in Germany. The study collected data on mental health (Brief Symptom Inventory - BSI-18), substance use, somatic health (Opiate Treatment Index Health-Symptoms-Scale - OTI-HSS), opioid craving (visual analogue scale), and withdrawal symptoms (Short Opiate Withdrawal Scale) at baseline (t0) and after 3 (t3), 6 (t6) and 12 (t12) months. Physicians documented side effects as adverse events (AEs) and adverse drug reactions (ADRs). RESULTS: Three-quarters of the enrolled study participants (N = 180) were male. The average age was 44.4 years. Patients were opioid-dependent for 23 years and had been in OAT for almost seven years on average. After 12 months, 60.6% were still being treated with SROM. Mental health improved significantly under SROM treatment between t0 and t12. The intention-to-treat (ITT), as well as the per-protocol (PP) analysis, shows a statistically significant improvement of the mean Global Severity Index (GSI) of the BSI-18 value of 20% (ITT) and 24% (PP). Physical health also improved significantly under SROM treatment. There were no statistically significant changes in the use of cannabis, cocaine, amphetamines, and tranquillizers in the past 30 days, but heroin use, intravenous consumption, and the number of drinking days significantly decreased. CONCLUSIONS: This study provides some of the first long-term data on OAT with SROM under routine care conditions. SROM treatment is an effective alternative for a subgroup of opioid-dependent patients with an unsatisfactory course of OAT or in cases where undesirable side effects due to alternative substances have occurred. ETHICAL STATEMENT: The study protocol was approved by the Ethics Committee of the Chamber of Physicians in Hamburg in March 2016 (No. PV5222). The study was conducted by following the Declaration of Helsinki and is registered with the German Register of Clinical Trials (DRKS, ID: DRKS00010712).

[Opioid Substitution Treatment in Germany: Physicians' View on the Effects of the 3rd Revision of the Narcotic Drugs Prescription Ordinance]. / Die Substitutionstherapie Opioidabhängiger in Deutschland: Auswirkungen der 3. BtMVVÄndV aus der Sicht substituierender Ärztinnen und Ärzte.

STUDY AIM: Opioid substitution treatment (OST) is the most effective drug treatment for opioid dependence worldwide. This form of therapy is also well established in Germany. Nevertheless, there are gaps in the provision of care, especially in rural areas and some states, due to a decreasing number of physicians involved in implementing the substitution programs. The 3rd revision of the Narcotic Drugs Prescription Ordinance (NDPO), which came into force in 2017, transferred medical therapeutic tasks of OST to the policy-making power of the German Medical Association. This comprehensive reform of the general conditions for OST led to greater legal certainty for this form of treatment. The present study aimed to analyze the effects of the 3rd revision of the Narcotic Drugs Prescription Ordinance from the providers' perspective. METHODS: Between August and December 2019, a questionnaire on individual experiences with the changes implemented in 3rd revision of the Narcotic Drugs Prescription Ordinance was sent by the Federal Opium Agency and the Associations of Statutory Health Insurance Physicians of the chosen federal states to 2,503 physicians implementing the substitution program in Germany as well as 563 physicians in Hamburg, Bavaria, North Rhine-Westphalia and Saxony who were not or no longer involved in this field of medical practice.The evaluation distinguished between physicians with and without further training in addiction medicine and between urban and rural districts. RESULTS: The response rate of physicians was 34.1%. The average age was 57.9 (±8.7) years, and 64.5% were male. The most relevant changes of the NDPO revision were found to be no time limit for achieving opioid abstinence (85.3%), new assessment and treatment using additional psychotropic substances (71.0%), extending take-home regulation to a maximum of 30 days (70.0%) and greater legal certainty (66.2%). Widening of consultative care up to 10 patients met with little approval (14.8%); 36.7% did not believe that care of substituted patients was assured either now or in the future. CONCLUSIONS: The NDPO revisions were considered to be relevant in terms of increased legal certainty and treatment liberties. Information was needed in rural areas, among physicians who carried out substitution therapy without advanced training in addiction medicine and physicians no longer involved in substitution therapy.

Addiction Recovery Among Opioid-Dependent Patients Treated With Injectable Subcutaneous Depot Buprenorphine: Study Protocol of a Non-randomized Prospective Observational Study (ARIDE).

Introduction: Once-weekly or once-monthly injectable depot buprenorphine is a new opioid substitution treatment (OST) medication that provides clinically relevant plasma concentrations without daily peaks. Together with a high tolerability and acceptance reported by patients, the prolonged release of injectable depot buprenorphine might have beneficial implications on the patients' quality of life and social participation. The primary objective of this prospective non-interventional observational study is to evaluate the effects of subcutaneous injectable depot buprenorphine on the quality of life of patients in routine OST care in Germany. Secondary outcomes like illicit substance use, psychological distress, social participation and activity are assessed to provide an overall evaluation toward addiction recovery. Methods and Analysis: The present study is a non-randomized prospective observational study with a control group (treatment-as-usual). To ensure comparability between both patient groups, suitable control patients (n = 213) from the same OST unit will be matched pairwise to each patient treated with injectable depot buprenorphine (n = 213). Matching variables are gender, duration of OST, take-home prescription and psychosocial functioning (according to the Global Assessment of Functioning scale). Primary study endpoint is the difference of change in quality of life, assessed with the recently developed Opioid Substitution Treatment Quality of Life scale (OSTQOL), within the depot buprenorphine group between baseline and month 12. The primary analysis will be carried out according to the intention-to-treat principle (ITT) by comparing OSTQOL mean scores using dependent t-tests. For secondary analyses, group comparisons will be done by mixed model approaches with baseline OSTQOL score and the (pairwise) cluster term as covariates. Discussion: The study combines clinical, routine OST care data with relevant patient reported outcome data. The pairwise matching allows conclusions on effects of different OST medications. The study findings will provide new insights in the addiction recovery processes of OST patients treated with depot buprenorphine. Ethics and Dissemination: The study protocol has been approved by the Ethics Committee of the Hamburg Chamber of Physicians (Ärztekammer Hamburg) (reference number: PV7078). The study results will be disseminated through peer-reviewed publications and presentations on scientific conferences. Clinical Trial Registration: German Clinical Trials Register DRKS-ID: DRKS00020797.

Switching opioid-dependent patients in substitution treatment from racemic methadone, levomethadone and buprenorphine to slow-release oral morphine: Analysis of the switching process in routine care.

Since 2015 slow-release oral morphine (SROM) is approved for opioid substitution treatment (OST) in Germany. The SROMOS study (efficacy and tolerability of slow-release oral morphine in opioid substitution treatment) evaluates the efficacy and safety of SROM in routine care. This article describes the switching process from racemic methadone, levomethadone and buprenorphine to SROM. Between July 2016 and November 2017 180 patients in 23 study centers in Germany were included in the prospective, non-interventional, naturalistic observational study. Patients were already in OST and switched from a previous medication to SROM. The switching process was analyzed during a period of fourteen days. Data were available for 169 participants. The switching process had a different progression depending on premedication and pre dosage. On the fourteenth day of SROM treatment patients switched from racemic methadone took an average dosage of 922.2 mg/day, from levomethadone 801.0 mg/day and from buprenorphine 626.7 mg/day. Average conversion ratio racemic methadone to SROM was 1:11.8, levomethadone to SROM 1:17.4 and buprenorphine to SROM 1:58.0. This study provides the first data on the switching process from buprenorphine to SROM. Average dose ratio racemic methadone to SROM on the fourteenth day of treatment was considerably higher than recommended in the prescribing information.

Brain Activation during Perception and Anticipation of Dyspnea in Chronic Obstructive Pulmonary Disease.

Background: Dyspnea is the impairing cardinal symptom in COPD, but the underlying brain mechanisms and their relationships to clinical patient characteristics are widely unknown. This study compared neural responses to the perception and anticipation of dyspnea between patients with stable moderate-to-severe COPD and healthy controls. Moreover, associations between COPD-specific brain activation and clinical patient characteristics were examined. Methods: During functional magnetic resonance imaging, dyspnea was induced in patients with stable moderate-to-severe COPD (n = 17) and healthy control subjects (n = 21) by resistive-loaded breathing. Blocks of severe and mild dyspnea were alternating, with each block being preceded by visually cued anticipation phases. Results: During the perception of increased dyspnea, both patients and controls showed comparable brain activation in common dyspnea-relevant sensorimotor and cortico-limbic brain regions. During the anticipation of increased dyspnea, patients showed higher activation in hippocampus and amygdala than controls which was significantly correlated with reduced exercise capacity, reduced health-related quality of life, and higher levels of dyspnea and anxiety. Conclusions: This study suggests that patients with stable moderate-to-severe COPD show higher activation in emotion-related brain areas than healthy controls during the anticipation, but not during the actual perception of experimentally induced dyspnea. These brain activations were related to important clinical characteristics and might contribute to an unfavorable course of the disease via maladaptive psychological and behavioral mechanisms.

Electronic Cigarettes in Germany: Patterns of Use and Perceived Health Improvement.

AIMS: The aim of the study was to characterize e-cigarette users in terms of their consumption patterns, motives, and the perceived health benefits they experience from using e-cigarettes. DESIGN: The study was a cross-sectional online survey in 2015. A total of 3,320 German e-cigarette users were enrolled. A total of 91.5% were former tobacco smokers, 7.5% used both e-cigarettes and tobacco products, 1.0% were never-smokers. RESULTS: No differences were found between ex-smokers and dual users with regard to sociodemographic and smoking history (mean age 40.8 years, 81% men, 45% with a high school degree or above). Both groups had smoked 26.4 tobacco cigarettes a day for 22 years, had unsuccessfully tried to quit smoking using various other nicotine replacement products, and had used e-cigarettes for an average of 2 years. Ex-smokers consumed lower nicotine strength and more liquid per month, experienced more positive health changes, and had made vaping their hobby. Never-smokers were about 5 years younger, used liquid without nicotine and without tobacco flavor, and had no physical dependency. CONCLUSIONS: E-cigarettes were primarily used as an alternative to smoking and a substitute for nicotine. More dual users than ex-smokers used e-cigarettes in places where smoking is forbidden. Positive health changes were more pronounced in ex-smokers than dual users.

Structural Brain Changes in Patients With COPD.

BACKGROUND: Patients with COPD suffer from chronic dyspnea, which is commonly perceived as highly aversive and threatening. Moreover, COPD is often accompanied by disease-specific fears and avoidance of physical activity. However, little is known about structural brain changes in patients with COPD and respective relations with disease duration and disease-specific fears. METHODS: This study investigated structural brain changes in patients with COPD and their relation with disease duration, fear of dyspnea, and fear of physical activity. We used voxel-based morphometric analysis of MRI images to measure differences in generalized cortical degeneration and regional gray matter between 30 patients with moderate to severe COPD and 30 matched healthy control subjects. Disease-specific fears were assessed by the COPD anxiety questionnaire. RESULTS: Patients with COPD showed no generalized cortical degeneration, but decreased gray matter in posterior cingulate cortex (whole-brain analysis) as well as in anterior and midcingulate cortex, hippocampus, and amygdala (regions-of-interest analyses). Patients' reductions in gray matter in anterior cingulate cortex were negatively correlated with disease duration, fear of dyspnea, and fear of physical activity. Mediation analysis revealed that the relation between disease duration and reduced gray matter of the anterior cingulate was mediated by fear of physical activity. CONCLUSIONS: Patients with COPD demonstrated gray matter decreases in brain areas relevant for the processing of dyspnea, fear, and antinociception. These structural brain changes were partly related to longer disease duration and greater disease-specific fears, which might contribute to a less favorable course of the disease.

Social comparison and anxious mood in pulmonary rehabilitation: the role of cognitive focus.

OBJECTIVES: Comorbid anxiety is highly prevalent in Chronic Obstructive Pulmonary Disease (COPD), and it is related to increased morbidity and mortality. It has consistently been found that social comparison has substantial impact on mood. However, despite the strong social component of pulmonary rehabilitation, the effect of social comparison processes on anxiety has not been explored in this context. DESIGN: Participants were 43 COPD patients enrolled in a 3-week pulmonary rehabilitation programme. We tested in a longitudinal design the relationship between social comparison and assimilation and contrast at the beginning of rehabilitation and anxious mood at the end of the programme. METHODS: Using moderator analysis, we tested whether perceived similarities and differences to upward and downward social comparison standards influence the relationship between comparison direction at the beginning of the programme and anxious mood at the end of the programme. RESULTS: The relationship between social comparison at the start of rehabilitation and anxious mood at the end of the programme was dependent on assimilation and contrast to upward and downward standards. Downward assimilation and upward contrast were related to a stronger relationship of upward and downward social comparison and anxious mood. CONCLUSION: This study demonstrates the important role of social comparison focus in moderating beneficial effects of pulmonary rehabilitation. Downward assimilation and upward contrast might be important targets in reducing anxiety in pulmonary rehabilitation.

The impact of anxiety and depression on outcomes of pulmonary rehabilitation in patients with COPD.

BACKGROUND: Anxiety and depression are prevalent comorbidities in COPD and are related to a worse course of disease. The present study examined the impact of anxiety and depression on functional performance, dyspnea, and quality of life (QoL) in patients with COPD at the start and end of an outpatient pulmonary rehabilitation (PR) program. METHODS: Before and after PR, 238 patients with COPD (mean FEV(1) % predicted = 54, mean age = 62 years) underwent a 6-min walking test (6MWT). In addition, anxiety, depression, QoL, and dyspnea at rest, after the 6MWT, and during activities were measured. RESULTS: Except for dyspnea at rest, improvements were observed in all outcome measures after PR. Multiple regression analyses showed that before and after PR, anxiety and depression were significantly associated with greater dyspnea after the 6MWT and during activities and with reduced QoL, even after controlling for the effects of age, sex, lung function, and smoking status. Moreover, before and after PR, anxiety was related to greater dyspnea at rest, whereas depression was significantly associated with reduced functional performance in the 6MWT. CONCLUSIONS: This study demonstrates that anxiety and depression are significantly associated with increased dyspnea and reduced functional performance and QoL in patients with COPD. These negative associations remain stable over the course of PR, even when improvements in these outcomes are achieved during PR. The results underline the clinical importance of detecting and treating anxiety and depression in patients with COPD.