Novel medications to treat addictive disorders.
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ABSTRACT:
SUBMITTER: Montoya ID
PROVIDER: S-EPMC2610431 | biostudies-literature | 2008 Oct
REPOSITORIES: biostudies-literature
Publications
Novel medications to treat addictive disorders.
Montoya Iván D ID Vocci Frank F
Current psychiatry reports 20081001 5
Recent discoveries about the effects of drugs of abuse on the brain and the mechanisms of their addictions; new chemical compounds, including immunotherapies; and new actions of available medications are offering many opportunities for the discovery and development of novel medications to treat addictive disorders. Furthermore, advancements in the understanding of the genetic and epigenetic basis of drug addiction and the pharmacogenetics of the safety and/or efficacy of the medications are prov ...[more]
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Project description:The purpose of this review is to present animal research models that can be used to screen and/or repurpose medications for the treatment of alcohol abuse and dependence. The focus will be on rats and in particular selectively bred rats. Brief introductions discuss various aspects of the clinical picture, which provide characteristics of individuals with alcohol use disorders (AUDs) to model in animals. Following this, multiple selectively bred rat lines will be described and evaluated in the context of animal models used to screen medications to treat AUDs. Next, common behavioral tests for drug efficacy will be discussed particularly as they relate to stages in the addiction cycle. Tables highlighting studies that have tested the effects of compounds using the respective techniques are included. Wherever possible the Tables are organized chronologically in ascending order to describe changes in the focus of research on AUDs over time. In general, high ethanol-consuming selectively bred rats have been used to test a wide range of compounds. Older studies usually followed neurobiological findings in the selected lines that supported an association with a propensity for high ethanol intake. Most of these tests evaluated the compound's effects on the maintenance of ethanol drinking. Very few compounds have been tested during ethanol-seeking and/or relapse and fewer still have assessed their effects during the acquisition of AUDs. Overall, while a substantial number of neurotransmitter and neuromodulatory system targets have been assessed; the roles of sex- and age-of-animal, as well as the acquisition of AUDs, ethanol-seeking and relapse continue to be factors and behaviors needing further study. This article is part of the Special Issue entitled "Alcoholism".
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Project description:Addictions are common, chronic, and relapsing diseases that develop through a multistep process. The impact of addictions on morbidity and mortality is high worldwide. Twin studies have shown that the heritability of addictions ranges from 0.39 (hallucinogens) to 0.72 (cocaine). Twin studies indicate that genes influence each stage from initiation to addiction, although the genetic determinants may differ. Addictions are by definition the result of gene × environment interaction. These disorders, which are in part volitional, in part inborn, and in part determined by environmental experience, pose the full range of medical, genetic, policy, and moral challenges. Gene discovery is being facilitated by a variety of powerful approaches, but is in its infancy. It is not surprising that the genes discovered so far act in a variety of ways: via altered metabolism of drug (the alcohol and nicotine metabolic gene variants), via altered function of a drug receptor (the nicotinic receptor, which may alter affinity for nicotine but as discussed may also alter circuitry of reward), and via general mechanisms of addiction (genes such as monoamine oxidase A and the serotonin transporter that modulate stress response, emotion, and behavioral control). Addiction medicine today benefits from genetic studies that buttress the case for a neurobiologic origin of addictive behavior, and some general information on familially transmitted propensity that can be used to guide prevention. A few well-validated, specific predictors such as OPRM1, ADH1B, ALDH2, CHRNA5, and CYP26 have been identified and can provide some specific guidance, for example, to understand alcohol-related flushing and upper GI cancer risk (ADH1B and AKLDH2), variation in nicotine metabolism (CYP26), and, potentially, naltrexone treatment response (OPRM1). However, the genetic predictors available are few in number and account for only a small portion of the genetic variance in liability, and have not been integrated into clinical nosology or care.
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Project description:BackgroundMany people with harmful addictive behaviors may not meet formal diagnostic thresholds for a disorder. A dimensional approach, by contrast, including clinical and community samples, is potentially key to early detection, prevention, and intervention. Importantly, while neurocognitive dysfunction underpins addictive behaviors, established assessment tools for neurocognitive assessment are lengthy and unengaging, difficult to administer at scale, and not suited to clinical or community needs. The BrainPark Assessment of Cognition (BrainPAC) Project sought to develop and validate an engaging and user-friendly digital assessment tool purpose-built to comprehensively assess the main consensus-driven constructs underpinning addictive behaviors.ObjectiveThe purpose of this study was to psychometrically validate a gamified battery of consensus-based neurocognitive tasks against standard laboratory paradigms, ascertain test-retest reliability, and determine their sensitivity to addictive behaviors (eg, alcohol use) and other risk factors (eg, trait impulsivity).MethodsGold standard laboratory paradigms were selected to measure key neurocognitive constructs (Balloon Analogue Risk Task [BART], Stop Signal Task [SST], Delay Discounting Task [DDT], Value-Modulated Attentional Capture [VMAC] Task, and Sequential Decision-Making Task [SDT]), as endorsed by an international panel of addiction experts; namely, response selection and inhibition, reward valuation, action selection, reward learning, expectancy and reward prediction error, habit, and compulsivity. Working with game developers, BrainPAC tasks were developed and validated in 3 successive cohorts (total N=600) and a separate test-retest cohort (N=50) via Mechanical Turk using a cross-sectional design.ResultsBrainPAC tasks were significantly correlated with the original laboratory paradigms on most metrics (r=0.18-0.63, P<.05). With the exception of the DDT k function and VMAC total points, all other task metrics across the 5 tasks did not differ between the gamified and nongamified versions (P>.05). Out of 5 tasks, 4 demonstrated adequate to excellent test-retest reliability (intraclass correlation coefficient 0.72-0.91, P<.001; except SDT). Gamified metrics were significantly associated with addictive behaviors on behavioral inventories, though largely independent of trait-based scales known to predict addiction risk.ConclusionsA purpose-built battery of digitally gamified tasks is sufficiently valid for the scalable assessment of key neurocognitive processes underpinning addictive behaviors. This validation provides evidence that a novel approach, purported to enhance task engagement, in the assessment of addiction-related neurocognition is feasible and empirically defensible. These findings have significant implications for risk detection and the successful deployment of next-generation assessment tools for substance use or misuse and other mental disorders characterized by neurocognitive anomalies related to motivation and self-regulation. Future development and validation of the BrainPAC tool should consider further enhancing convergence with established measures as well as collecting population-representative data to use clinically as normative comparisons.
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Project description:ObjectiveTo evaluate the long-term effects of a multilevel community intervention to improve the quality of prescription practice of potentially addictive medications (PAMs).DesignWe conducted a retrospective study, using anonymized data from the Norwegian prescription registry.SettingBased on an initiative from the GPs in Molde Municipality in Norway, a multilevel community intervention was initiated by the municipal chief physician in 2018. The intervention targeted GPs, patients, and the public.SubjectsWe retrieved prescription data from 26 of 36 GPs.Main outcome measuresBy using the standardized defined daily dose (DDD), we compared prescription of three groups of PAMs from before the intervention (2017) throughout the intervention in 2018, and through 2020 to determine long-term effects.ResultsThree years after the intervention, the GPs in our study sample prescribed 26% less opioids, 38% less benzodiazepines, and 16% less z-hypnotics. Overall prescription of PAMs decreased by 27%. The number of individuals receiving at least 90 DDD of benzodiazepines and z-hypnotics were reduced from 9 to 7 and 34 to 24 per 1000, respectively. Also, the number of individuals receiving two and three PAMs concomitantly were reduced.ConclusionAddressing prescription practice among GPs in a community as a joint intervention, combined with addressing patients and the public may be a feasible method to obtain long-term reduction of PAM prescriptions.Key pointsNon-therapeutic prescriptions of potentially addictive medications (PAMs) are both a public health concern and a frequent challenge in general practice.A multilevel community intervention, targeting general practitioners, patients, and the public, led to 27% reduction in prescription of PAMs.Both the number of daily users and concomitant use of several PAMs were reduced.The reduction in prescription persisted for three years.
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Project description:BackgroundMultimorbidity and prolonged use of addictive medications are prevalent among older patients, and known to increase the risk of adverse drug events. Yet, the relationship between these two entities has remained understudied.AimsThis study explored the association between multimorbidity burden and prolonged use of addictive medications in geriatric patients, adjusted for clinically important covariates. Furthermore, we identified comorbidity patterns in prolonged users.MethodsWe conducted a cross-sectional study on a consecutive sample of 246 patients, aged 65-90 years, admitted to a large public university hospital in Norway. We defined prolonged use of addictive medications as using benzodiazepines, opioids and/or z-hypnotics beyond the duration recommended by clinical guidelines (≥ 4 weeks). Multimorbidity was assessed with the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), based on diagnoses made by independent physicians.ResultsCompared to non-prolonged use, prolonged use was significantly more common among patients who had psychiatric (19/27, 70%), liver (19/22, 86%), upper gastrointestinal tract (21/32, 66%), musculoskeletal (52/96, 54%), or nervous system disorders (46/92, 50%). Patients with prolonged use had a higher multimorbidity burden than those without such use (CIRS-G score, mean = 7.7, SD = 2.7 versus mean = 4.6, SD = 2.2, p < 0.001). Multivariable logistic regression indicated a significant association between multimorbidity burden and prolonged addictive medication use (OR = 1.72, 95% CI 1.42-2.08). Predictive margins postestimation showed a systematic increase in the predicted CIRS-G scores when the number of addictive drug used increases.ConclusionsMultimorbidity is strongly associated with prolonged use of addictive medications. Multiple substance use may aggravate disease burden of older patients.
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