Non-drug Alternatives Research Articles

Generalized cue reactivity in dopamine neurons after opioids.

Cue reactivity is the maladaptive neurobiological and behavioral response upon exposure to drug cues and is a major driver of relapse. The leading hypothesis is that dopamine release by addictive drugs represents a persistently positive reward prediction error that causes runaway enhancement of dopamine responses to drug cues, leading to their pathological overvaluation compared to non-drug reward alternatives. However, this hypothesis has not been directly tested. Here we developed Pavlovian and operant procedures to measure firing responses, within the same dopamine neurons, to drug versus natural reward cues, which we found to be similarly enhanced compared to cues predicting natural rewards in drug-naïve controls. This enhancement was associated with increased behavioral reactivity to the drug cue, suggesting that dopamine release is still critical to cue reactivity, albeit not as previously hypothesized. These results challenge the prevailing hypothesis of cue reactivity, warranting new models of dopaminergic function in drug addiction, and provide critical insights into the neurobiology of cue reactivity with potential implications for relapse prevention.

The subjective value of social context in people who use cannabis.

Disordered cannabis use is linked to social problems, which could be explained by a subjective devaluation of nondrug social contexts and/or an overvaluation of cannabis-paired options relative to nondrug alternatives. To examine these hypotheses, measures to assess the subjective value of social- and/or cannabis-paired contexts were collected in people who use cannabis (n = 85) and controls (n = 98) using crowdsourcing methods. Measures included a cued concurrent choice task that presented two images (cannabis, social, social cannabis, and neutral images) paired with monetary options, hypothetical purchase tasks that included access to social parties with and without a cannabis "open bar," and the Social Anhedonia Scale (SAS). Little evidence was found to suggest that the cannabis group undervalued social contexts. People who used cannabis demonstrated a preference for social- versus neutral-cued options, and no preference for cannabis- versus social cannabis-cued options on the choice task. In addition, social party demand and SAS scores did not differ between groups. In contrast, we observed evidence for an overvaluation of cannabis context in people who use cannabis, including preference for social cannabis- versus social-cued options, and more disadvantageous choices for cannabis-cued options on the choice task, as well as more intense and inelastic demand for the social cannabis party compared to the social party. These results suggest that social problems associated with cannabis use could be at least partially explained by an overvaluation of cannabis-paired options, rather than devaluation of nondrug social-paired options, in the value calculations underlying drug use decisions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cocaine and heroin interact differently with nondrug reinforcers in a choice situation.

The present study used a rat choice model to test how cocaine or heroin economically interacted with two different nondrug reinforcers along the substitute-to-complement continuum. In Experiment 1, the nondrug alternative was the negative reinforcer timeout-from-avoidance (TOA)-that is, rats could press a lever to obtain a period of safety from footshock. One group of rats chose between cocaine and TOA and another group chose between heroin and TOA. The relative prices of the reinforcers were manipulated across phases while controlling for potential income effects. When cocaine was the reinforcer, rats reacted to price changes by increasing their allocation of behavior to the more expensive option, thereby maintaining relatively proportional intake of cocaine and TOA reinforcers across prices, suggesting these reinforcers were complements here. In contrast, when heroin became relatively cheap, rats increased allocation of income to heroin and decreased allocation of income to TOA, suggesting that heroin substituted for safety. Additionally, rats were willing to accept more footshocks when heroin was easily available. In Experiment 2, the nondrug alternative was saccharin, a positive reinforcer. Heroin and saccharin were complements, but there was no consistent effect of price changes on the allocation of behavior between cocaine and saccharin. As a model of the processes that could be involved in human drug use, these results show that drug-taking behavior depends on the type of drug, the type of nondrug alternative available, and the prices of both. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

INDICADORES DE APTIDÃO FUNCIONAL E COMPROMETIMENTO COGNITIVO EM IDOSOS

ABSTRACT Introduction: Cognitive losses are among the most prevalent events in the elderly population and can cause functional deficits. Among the available non-drug prevention and treatment alternatives, the increase in functional fitness levels is presented as an important strategy suggesting improvements in the physical and cognitive function of the elderly triggered by exercise. Objective: To determine the predictive power of functional fitness indicators and establish their cutoff points as discriminators of cognitive impairment in the elderly. Methods: The sample comprised 310 elderly people who answered a questionnaire comprising sociodemographic information, lifestyle habits, hospitalization in the last 12 months, presence of comorbidity, and the Mini-Mental State Examination. Functional fitness was assessed using the Hand Grip Strength (HGS) and sitting and rising from a chair tests. To identify predictors of cognitive impairment, analysis of Receiver Operating Characteristic (ROC) curves was adopted, with a confidence interval of 95% (95%CI). Subsequently, the cut-off points with their respective sensitivities and specificities were identified. The analyses were performed respecting the significance level of 5%. Results: It was observed that some functional fitness indicators showed significant Area Under the Curve (AUC), and the sit-and-stand test (AUC=0.72; 95%CI: 0.64-0.77) showed the best results. The best cut-off points for the HGS and sit-and-stand tests were 18,8 kgf and eight repetitions, respectively. Conclusion: The results of the present study allow us to conclude that the sit-to-stand test is moderately efficient in discriminating the presence of cognitive impairment in the elderly. Level of Evidence III; Study Cross-sectional.

OP109 The Conceptualization And Value Of A Disease Management Approach To HTA In Canada: Findings From A Qualitative Study

IntroductionOur objective was to conceptualize and assess the potential value of a disease management approach to health technology assessment (HTA) in Canada.MethodsWe conducted 18 semi-structured interviews between April 2022 and October 2022 to elicit informant views on potential opportunities for re-conceptualizing the decision-problem in HTA as a disease management problem versus a technology management problem. Participants were purposefully sampled from national and provincial HTA agencies and related organizations in Canada to achieve representation across the disease pathway including prevention, screening, and treatment, and the decision-making pathway including HTA organizations, expert committee members, and decision-makers. Data were analyzed using thematic organizations (based on the interview guide) and manual line by line coding of the data. Ethics approval was received from the Health Sciences Research Ethics Board at the University of Toronto.ResultsThree key features of a disease management approach to HTA (i.e., disease-based, multi-interventional, and dynamic) emerged from informants that differed from traditional HTA processes in Canada. The concept was generally not perceived to be a new idea – some informants indicating that it was implicit in the HTA analysis framework. There was general support for an explicit disease management approach to HTA if the impact of the approach could be demonstrated, if the assessment could be completed within an appropriate time frame, and if the assessment could include the equity, ethical and implementation domains of HTA. Informants indicated that the reconceptualization of HTA could lead to effective and efficient decision-making throughout a technology’s lifecycle, help breakdown system silos, and offer a platform for greater consideration of non-drug alternatives and upstream interventions. The impact of this approach was anticipated to contribute to a proactive health system that could improve population health, enhance the patient experience, and ensure appropriate stewardship of health care resources.ConclusionsA disease management approach to HTA has international relevance as an approach that could promote integrated, proactive, sustainable, and resilient health systems.

Choice between food and cocaine or fentanyl reinforcers under fixed and variable schedules in female and male rhesus monkeys.

Illicit drugs may be unpredictable in terms of the time and effort required to obtain them, and this can be modeled with variable- (VR) vs. fixed-ratio (FR) schedules. In a recent experiment (Zamarripa et al. 2023), the potency of cocaine to maintain choice was greatest under a VR (compared with a FR) when food was available under a FR schedule. The goal of the current study was to extend prior choice results with VR vs. FR schedules to a more efficient procedure with cocaine or fentanyl vs. food. Furthermore, the FR schedule of food delivery was manipulated to determine whether increased drug choice under a VR (compared with a FR) schedule depends on the size of the schedule of nondrug reinforcement. Adult female (n = 2) and male (n = 4) monkeys chose between cocaine (0-30µg/kg/injection) or fentanyl (0-1.0µg/kg/injection) and food (2 pellets/delivery) under a 5-component procedure. In different conditions, food was available under a FR 25, 50, or 100 and cocaine or fentanyl were available under FR or VR 100 schedules. Cocaine's potency to maintain choice was greatest under a VR 100 (compared with FR 100) when food was available under a FR 50 or 100, and fentanyl's potency to maintain choice was generally greatest under a VR 100 (compared with FR 100) when food was available under a FR 25 or 100. However, outcomes between FR and VR schedules with fentanyl were less robust compared with cocaine. Variability in the time and effort required to obtain illicit drugs could contribute to excessive allocation of behavior toward drug use at the expense of more predictable nondrug alternatives, supporting treatment or policies aimed at making drug access more predictable through agonist medications or a safe supply. The impact of variable requirements on drug choice may be reduced if nondrug reinforcers are relatively less costly, supporting the use of low-cost reinforcers in behavioral therapies like contingency management.

Using Drugs or Non-Drugs Alternatives to Alter Mental States in the Online, Virtual Era

Background: In the 1970s a body of literature was generated advocating the alternatives approach for drug misuse prevention and rehabilitation which encouraged healthy nonchemical behaviors leading to reinforcing moods. Although this behaviorally oriented approach was overshadowed with the popularity of cognitive therapy in the 1980s, many of the recommended alternative behaviors remain embedded in cognitive approaches for drug misuse prevention and rehabilitation. One objective of the present study was to replicate, in part, two studies conducted in the 1970s which examined usage patterns of non-drug alternatives. A second objective was to explore of the use of newer technologies like the internet and the smartphone to alter emotional states. A third objective was to examine perceived stress and discrimination experiences on preferences for drug and non-drug alternatives. Methods: Three questionnaires were administered: use of drugs and non-drug alternatives in response to everyday emotions; the Everyday Discrimination Scale; and the Perceived Stress Scale. A total of 483 adults participated; their mean age was 39 years. Results: The results revealed that non-drug alternatives were preferred to drugs in treating experiences of anxiety, depression, and hostility, and to induce pleasure. Drugs were used most often to deal with pain. Experiences of discrimination increased perceptions of stress, and stress, in turn, affected the use of drugs to cope with a range of emotions. Social media and virtual activities were not preferred methods for altering negative moods. Conclusions: Social media may actually be a contributor or cause of distress, rather than a means for reducing it.

Choice between food and cocaine reinforcers under fixed and variable schedules in female and male rhesus monkeys.

Illicit drugs like cocaine may be uncertain in terms of the time and effort required to obtain them. Behavior maintained by variable schedules resembles excessive drug-taking compared with fixed schedules. However, no prior research has examined fixed versus variable schedules in drug versus nondrug choice. The present study evaluated cocaine versus food choice under fixed- (FR) and variable-ratio (VR) schedules. The simpler food versus food and cocaine versus cocaine arrangements also were included. Adult female (n = 6) and male (n = 7) rhesus monkeys chose between cocaine (0.01-0.18 mg/kg/injection) and food (4 pellets/delivery), food and food (4 pellets/delivery), or cocaine and cocaine (0.018-0.03 mg/kg/injection) under FR and VR 100 and 200 schedules. In cocaine versus food choice, cocaine's potency to maintain choice was greatest when available under a VR 100 or 200 schedule and food under an FR schedule and was lowest when cocaine was available under an FR 200 schedule and food was available under a VR 200 schedule. In food versus food choice, males chose food associated with a VR schedule more than food associated with an FR schedule. In cocaine versus cocaine choice, females and males chose cocaine associated with a VR schedule more than cocaine associated with an FR schedule, particularly under VR 200. These findings suggest that uncertainty in terms of time and effort required to obtain cocaine, or perhaps the occasional low-cost access that results from VR schedules, results in greater allocation of behavior toward drug reinforcers at the expense of more certain, nondrug alternatives. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Give prescribers access to non-drug alternatives to antidepressants and opioids, says NHS

NHS England has published a new framework aimed to “empower” commissioners in England to better support patients who are taking prescribed drugs associated with dependence or withdrawal. The framework, published on 2 March 2023, focuses on five types of medicines, including opioids, benzodiazepines, Z-drugs, gabapentinoids and antidepressants, and aims to reduce inappropriate prescribing in primary […]

Provider knowledge, beliefs, and self-efficacy to deprescribe opioids and sedative-hypnotics.

While many studies have assessed and measured patient attitudes toward deprescribing, less quantitative research has addressed the provider perspective. We thus sought to describe provider knowledge, beliefs, and self-efficacy to deprescribe, with a focus on opioids and sedative-hypnotics. An electronic anonymous survey was distributed to primary care providers at Kaiser Permanente Washington. Two reminder emails were sent. The survey included 10 questions on general deprescribing, and six questions each specific to opioid and sedative-hypnotic deprescribing. Knowledge questions used a multiple-choice response option format. Questions addressing beliefs and self-efficacy (i.e., confidence) used a 0-10 Likert scale. Scales were dichotomized at ≥7 to define agreement (belief questions) or confidence (self-efficacy questions). We calculated descriptive statistics to summarize the responses. Of 370 eligible primary care providers, 95 (26%) completed the survey. For general deprescribing questions, a majority believed that lack of patient willingness, withdrawal symptoms and fear of symptom return, and time constraints impeded deprescribing. Approximately half chose the correct answers about opioid deprescribing, 21% were confident that they could alleviate patient concerns about opioid tapering, and 32% were confident managing chronic non-cancer pain without opioids. For sedative-hypnotics, 64%-87% of respondents correctly answered questions about risks and the relative effectiveness of alternatives, but only one-third correctly answered a question about sedative-hypnotic tapering. Roughly half were confident in their ability to successfully engage patients in sedative deprescribing conversations and select alternatives. Only 54% and 34% were confident in writing a tapering protocol for opioids and sedative-hypnotics, respectively. Results suggest that raising provider awareness of patient willingness to deprescribe, addressing knowledge gaps, and increasing self-efficacy for deprescribing are important targets for improving deprescribing. Support for writing tapering protocols and prescribing evidence-based drug and non-drug alternatives may be important to improve care.

The gut-brain axis: effect of antibiotics on canine drug-resistant idiopathic epilepsy

Approximately thirty percent of the dogs with idiopathic epilepsy develop multidrug resistance. Therefore, the search for new non-drug treatment alternatives is important. There is a growing interest in the gut-brain axis and its role in the pathogenesis of epilepsy. The gut microbiota can influence brain function by different neural, endocrine, immune and metabolic pathways, but this process is not yet fully understood. In this study, five client-owned dogs with drug-resistant, idiopathic epilepsy received amoxicillin-clavulanic acid as add-on orally (mean duration 32 days (range 21-64 days)). The mean isolated epileptic seizure frequency of these five dogs was 3.3/ week (range 2.5-6.5) with a mean cluster seizure frequency of 0.9/week (range 0.4-1.5). During the amoxicillin-clavulanic acid treatment, three dogs showed complete seizure freedom, one dog showed an 80% decrease of both isolated epileptic seizure and cluster seizure frequency, and one dog showed an increase in isolated epileptic seizure and cluster seizure frequency of 54% and 38%, respectively. In the two-month follow-up period after cessation of the antibiotic administration, the mean isolated epileptic seizure and cluster seizure frequency increased again to 1.5 seizures/week (range 0.9-2.8) and 0.4 clusters/week (range 0.4-0.6), respectively. The preliminary results in this study highlight the need for future research into the role of the canine gut-brain axis in idiopathic epilepsy.

Effects of Audio Brain Entrainment on Korean People with Mild Insomnia.

Sleep health has become an important healthy lifestyle. Research has shown that almost one-fifth of the Korean adult population does not have sufficient sleep. The lack of sleep is associated with significant medical, psychological, social, and economic issues. People are not only yearning for sufficient sleep but the quality of sleep as well. Usually, the obvious choice will be the use of pharmaceuticals however, these often have various side effects, and the lasting use of these medications could become a concern. Therefore, new non-drug alternatives are sought after. Audio brain entrainment is a procedure that modules neural activities by synchronizing brainwave frequency with pulse tones. By producing frequency tones for the deep sleep stage, it promotes a good night's sleep. In this paper, we developed a pillow integrated with the audio speakers that produce alpha and theta beats that should help improve sleep. Sleep polysomnography was performed on 10 people to compare the effects of the audio stimulus. Initial results showed a positive effect on sleep onset latency, indicating that sleep induction happened. This noninvasive stimulation technique can be a promising candidate for wearable bioelectronics medicine and further neuroscience research.

Cocaine falls into oblivion during volitional initiation of choice trials.

When facing a choice, most animals quit drugs in favour of a variety of nondrug alternatives. We recently found, rather unexpectedly, that choice of the nondrug alternative is in fact inflexible and habitual. One possible contributing factor to habitual choice is the intermittency and uncontrollability of choice trials in previous studies. Here, we asked whether and to what extent volitional control over the occurrence of choice trials could change animals' preference by preventing habitual choice. To do so, rats were trained to nosepoke in a hole to trigger the presentation of two operant levers: one associated with cocaine, the other with saccharin. Rats were then free to choose among the two levers to obtain the corresponding reward, after which both levers retracted until rats self-initiated the next choice trial. Overall, we found that volitional control over choice trials did not change preference. Most rats preferred saccharin over cocaine and selected this option almost exclusively. Intriguingly, after repeated choice and consumption of saccharin, rats transiently lost interest in this option (i.e., due to sensory-specific satiety), but they did not switch to cocaine, preferring instead to pause during long periods of time before reinitiating a choice trial for saccharin. This finding suggests that during volitional initiation of a choice trial, rats fail to consider cocaine as an option. We discuss a possible associative mechanism to explain this perplexing behaviour.

Indications for Left Atrial Appendage Occlusion in the United States and Associated In-Hospital Outcomes: Results From the NCDR LAAO Registry.

The Food and Drug Administration approved left atrial appendage occlusion with the Watchman device for patients who are at increased stroke risk and are suitable for oral anticoagulation but who have an appropriate reason to seek a nondrug alternative. These broad criteria raise the question of their interpretation in clinical practice. There is a lack of studies comprehensively evaluating the indications for Watchman implantation among a large series of patients from contemporary, real-world practice in the United States. We used the National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry to identify Watchman procedures performed between 2016 and 2018. We assessed procedural indications for Watchman implantation in the United States and evaluated the association between procedural indications and in-hospital adverse events. A total of 38 314 procedures were included. The mean patient age was 76.1±8.1 years, and 58.9% were men. The mean CHA2DS2-VASc score was 4.8±1.5, whereas the mean hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) score was 3.0±1.1. Prior stroke or transient ischemic attack was reported in 40.2% and prior bleeding in 70.1%, with gastrointestinal bleeding being most common (41.9%). The most common site-reported procedural indications for Watchman implantation were increased thromboembolic risk (64.8%) and history of major bleed (64.3%), followed by high fall risk (35.5%). Most (71.9%) had ≥2 procedural indications. Patients with high fall risk had increased risk of in-hospital adverse events (adjusted OR, 1.12; P=0.025), but no other differences were found in the risk of in-hospital adverse events by procedural indication. Among patients in the National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry, the most common procedural indications for Watchman implantation were increased thromboembolic risk, history of major bleed, and high fall risk. A majority of patients had multiple procedural indications. High fall risk conferred a modestly increased risk of in-hospital adverse events.

Effects of Co‐Use of Nicotine on Cocaine‐Food Choice in Socially Housed Female and Male Cynomolgus Monkeys

Cocaine use disorder (CUD) continues to be a major public health problem worldwide with 2.0 million Americans reporting current cocaine use. At present there are no FDA‐approved pharmacotherapies for CUD. An important consideration in evaluating mechanisms of CUD and potential treatment strategies is the observation that most individuals suffering from CUD also use tobacco products. However, most preclinical studies investigating cocaine do not include co‐exposure with nicotine. For these studies, socially housed female and male monkeys (N= 5/sex) self‐administered cocaine (saline, 0.001‐0.1 mg/kg/inj) under a concurrent schedule with food (1.0‐g banana‐flavored food pellets) as the alternative reinforcer during daily 1‐hr sessions. Under these conditions, the frequency of cocaine choice increases in a dose‐dependent manner; there were individual‐subject differences in sensitivity, but when nicotine was added to the cocaine solution, we individually chose the highest cocaine dose which resulted in <20% cocaine choice for each monkey. When increasing doses of nicotine (0.01‐0.056 mg/kg/inj) were added to the cocaine solution, non‐reinforcing doses of cocaine were chosen (i.e., >80% drug choice) in 8 of the 10 monkeys; importantly, in no cases were these nicotine doses chosen over food. These data suggest that when a non‐reinforcing dose of nicotine is added to a non‐reinforcing dose of cocaine, drug choice increases to the point that the combination is chosen over the non‐drug alternative. Next, environmental manipulations were studied to determine whether the cocaine+nicotine combination was more resistant to changes than cocaine alone. For these studies, we used a delay discounting procedure similar to that described by Woolverton and colleagues (Huskinson et al., 2015, 2016). We compared the indifference point (IP; 50% choice between cocaine and food) when a preferred dose of cocaine was available vs. food and cocaine was delayed, to the IP value when a lower cocaine dose + nicotine was available vs. food. We found that in each case, the IP value was greater for the cocaine+nicotine combination compared with the cocaine alone choice. These findings suggest (1) that co‐abuse of nicotine and cocaine can potentiate the reinforcing effects of cocaine and (2) that manipulations designed to decrease cocaine choice are less effective under conditions in which co‐use of nicotine is studied. These preliminary studies did not reveal sex differences or effects of social rank. At present, it is not known how nicotine and cocaine interact. One hypothesis is that both drugs together produce entirely novel neurobiological effects compared with either one alone. The behavioral endpoints may look additive, as shown in our preliminary data, but the mechanisms are probably not simply additive. These studies may lead to a more personalized medicine approach to treating CUD.

Stakeholders' views on the use of psychotropic medication in older people: a systematic review.

Backgroundpsychotropic medication use has been shown to increase with age and has been associated with increased risk of falls, strokes and mortality. Various guidelines, regulations and tools have been developed to reduce inappropriate prescribing, but this remains high. In order to understand the reasons for this, we aimed to systematically review healthcare professionals’, patients’ and family caregivers’ attitudes towards the use of psychotropic medication in older people.Methodsa systematic literature search was carried out from inception to September 2020 using PUBMED, EMBASE, PsycINFO and CINAHL and hand-searching of reference lists. Included studies investigated stakeholder views on psychotropic in adults over the age of 65. Findings were thematically synthesised.Resultsoverall, there was an acceptance of long-term psychotropic medication for older people both living in the community and in residential care. While healthcare professionals were aware of guidelines for the use of benzodiazepines and psychotropic medicines, they identified barriers to following them on individual, team and organisational levels. Alternative non-pharmacological approaches were not always available or accepted by patients.Conclusionpsychotropic medicine use in older adults remains a complex issue, which needs to be addressed on a broad level. Attitudes of older people and healthcare professionals encourage long-term use. Meanwhile, various internal and external factors act as barriers to the use of non-drug alternatives in this population. In order to reduce overprescribing of psychotropics, there is a need to increase the acceptability and accessibility of alternative interventions in both care homes and the community.

Professional perspectives on applying the NICE and British Psychological Society Guidelines for the management of Behaviours that Challenge in dementia care: an e-survey.

ObjectivesBehaviours that challenge (BtC) reflect the most costly and burdensome aspects of dementia where non‐pharmacological interventions rather than antipsychotic medication have been recommended as first‐line approaches for over a decade (NICE 2006). This paper outlines professionals’ views about their application of the Dementia NICE Guideline 97 (2018) and a British Psychological Society, Division of Clinical Psychology (BPS‐DCP) Briefing paper (2013) on alternatives to antipsychotics.MethodsA mixed‐methods 34‐item e‐survey, with five items about the use of the NICE Guideline 97 (2018) and the BPS‐DCP Briefing paper (2013) for the management of BtC, was conducted. Participants were recruited through multidisciplinary professional dementia networks across the United Kingdom. Quantitative data were descriptively summarized and thematic analysis of open‐ended questions undertaken.ResultsTwo hundred and forty‐seven participants completed the questions relating to guidelines. Mean ratings of ‘moderately useful’ for both the NICE and BPS‐DCP guidance were obtained across professions and geographical locations, with the exception of psychiatrists who rated the NICE guidance as ‘slightly useful’. The qualitative themes identified were a mix of positive and cautionary perspectives, relating to ‘evidence base’, the ‘accessibility of the guides’, ‘problems with implementation’, and ‘lack of detail and clarity’.ConclusionProfessionals were cautiously positive regarding the guidance for BtC management, but highlighted a need for improved clarity about the use of non‐pharmacological approaches, and more specificity about how these can be implemented in clinical settings. Tailored ‘setting‐specific’ toolkits are required to update and refine the BPS‐DCP (2013) if the aspirations of the NICE Dementia Guideline 97 (2018) are to inform professional practice.Practitioner Points Owing to major concerns about the problematic side effects of using psychotropics in the treatment of behaviours that challenge (BtC), there is a need for national guidance on the use on non‐drug alternatives.The NICE (2018) guidance was seen by participants as accessible and clear but lacking in detail in the use of non‐pharmacological interventions, which are the first‐line treatments for BtC.The BPS Guidelines on ‘Alternatives to antipsychotics’ (2013) were seen as having good structured advice for allocating non‐pharmacological resources but were lacking in flexibility for meeting individual needs or what might be an acceptable fit for clinical services.The findings suggest that we need to develop UK‐wide bespoke specific advice for practitioners and services for both the use and the delivery of non‐pharmacological evidence‐based interventions for BtC.

What is the significance of guidelines in the primary care setting? : Results of an exploratory online survey of general practitioners in Germany.

Medical guidelines aim to ensure that care processes take place in an evidence-based and structured manner. They are especially relevant in outpatient primary care due to the wide range of symptoms and clinical pictures. In German-speaking countries, there is a lack of current findings documenting general practitioners’ opinions and experiences regarding guidelines, their expectations and their views on what improvements could be made to increase the use of this type of evidence-based instrument in the primary care setting. Between April and August 2020, a total of 3098 general practitioners were surveyed in the states of Baden–Württemberg, Hesse and Rhineland–Palatinate via an online questionnaire. Alongside the descriptive evaluation, t‑testing was used to determine significant differences between two independent sampling groups. A factor analysis was also used to cluster the expectations of those surveyed regarding the fulfilment of requirements relating to guidelines. A total of 52% of those surveyed have a positive view of guidelines. Overall, guidelines are associated with an increased evidence-based approach (69%), standardisation of diagnosis and treatment (62%) and a reduction in overprovision or underprovision of care (57%). In all, 62% of the physicians who implemented guidelines observed positive effects on the quality of care provided, and 67% reported that the implementation of guidelines improved the quality of their diagnostic or therapeutic skills. However, implementation is often seen as being complicated (43%) and restricting the physician’s ability to act independently (63%). Survey participants suggested that guidelines could be optimised by giving greater consideration to nondrug alternatives (46%), focusing on issues related to quality of life (42%) and offering a comparative assessment of various treatment options (39%). In order to further promote the attractiveness of guidelines for primary care the design of guidelines should be oriented more towards their application; they should be well-presented to make them easier to implement. The scope of action available to the physician should be stressed. The guidelines should provide recommendations on opportunities for the delegation of tasks within practice teams.Supplementary InformationThe online version of this article (10.1007/s10354-021-00849-3) contains supplementary material, which is available to authorized users.

Pharmacokinetics trumps pharmacodynamics during cocaine choice: a reconciliation with the dopamine hypothesis of addiction.

Cocaine is known to increase brain dopamine at supranormal levels in comparison to alternative nondrug rewards. According to the dopamine hypothesis of addiction, this abnormally large dopamine response would explain why cocaine use is initially highly rewarding and addictive. Though resting on solid neuroscientific foundations, this hypothesis has nevertheless proven difficult to reconcile with research on cocaine choice in experimental animals. When facing a choice between an intravenous bolus of cocaine and a nondrug alternative (e.g., sweet water), both delivered immediately after choice, rats do not choose the drug, as would be predicted, but instead develop a strong preference for the nondrug alternative. Here we report evidence that reconciles this finding with the dopamine hypothesis of addiction. First, a systematic literature analysis revealed that the delays of effects of intravenous cocaine on nucleus accumbens dopamine are of the order of tens of seconds and are considerably longer than those of nondrug reward. Second, this was confirmed by measuring response times to cocaine omission during self-administration as a behavioral proxy of these delays. Finally, when the influence of the drug delays was reduced during choice by adding an increasing delay to both the drug and nondrug rewards, rats shifted their choice to cocaine. Overall, this study suggests that cocaine is indeed supranormal in reward magnitude, as postulated by the dopamine hypothesis of addiction, but is less preferred during choice because its pharmacokinetics makes it an inherently more delayed reward than the alternative. Reframing previous drug choice studies in rats as intertemporal choice studies reveals that the discounting effects of delays spare no rewards, including supranormal ones, and that during choice, pharmacokinetics trumps pharmacodynamics.

0471 24-Month Post Marketing Safety Surveillance Data of a Novel Continuous Release and Absorption Melatonin (CRA-Melatonin) Delivery System, Confirms Favorable Safety Profile

Abstract Introduction The awareness of sleep disorders having negative health consequences, including hypertension, diabetes, obesity, depression, heart attack and stroke, has sharply escalated in recent years. Traditional treatments, including benzodiazepenes, non-benzodiazepenes, anti-depressants and non-prescription first-generation antihistamines, come with limitations in efficacy, safety and tolerability. The search for non-drug alternatives continues. The novel, well tolerated CRA-melatonin was shown in a randomized, crossover, pharmacokinetic (PK) study versus the leading marketed melatonin to achieve quick uptake and then continuous release and absorption for up to 7 hours. No safety or tolerability issues were observed. The Remfresh Safety Update at 24 months (REMSU24), a real-world safety surveillance study was conducted to confirm the previously observed safety profile of CRA-melatonin. Methods An independent call center with pharmacovigilance-trained health care personnel in accordance with FDA guidelines on properly reporting events, was retained to receive and record customer questions, product issues and adverse events (AEs). The study was conducted from March 9, 2017 to March 9, 2019. Results An estimated 320,255 patients used CRA-melatonin during the surveillance period. There were no serious AEs. The self-reporting rates of non-serious AEs were low with only 51 events recorded, a 0.016% event rate. The two most frequent AEs, headaches and nightmares are known comorbidities of insomnia. As background, there had been no treatment emergent adverse events for CRA-melatonin in the PK trial. Conclusion CRA-melatonin’s extended 7-hour PK profile may be an effective and well-tolerated baseline therapy to improve sleep. These results confirm the favorable safety and tolerability trend observed in the PK study. In REMSU24, the scatter of reported adverse events could not be separated from what could be expected in the untreated general population. Support This study was supported by Physician’s Seal LLC