MY CUP RUNNETH OVER: IDENTIFYING AND TREATING ALCOHOL USE DISORDER
Learning Objectives • Describe the neurobiological impact of alcohol abuse • Improve identification of patients with alcohol misuse and abuse • Integrate currently available practices to treat alcohol abuse with individualized treatment plans
The Cost of Alcohol • Worldwide, the estimated 12-month adult prevalence of alcohol use disorder (AUD) is 8.5% • Estimated lifetime prevalence of AUD is 20% • In the US, AUD has been estimated at 13.9% for 12-month prevalence and 29.1% for lifetime prevalence • Alcohol is the third-leading preventable cause of death in the US • AUD costs the US $223.5 billion annually Reus et al. AM J Psychiatry 2018;175(1):86-90.
The COVID-19 Pandemic and the Rise of AUD • Following the outbreak of COVID-19, governments across the world implemented social distancing measures to slow the rate of infection • Individuals with addiction are more likely to be impacted by poverty, physical and mental health vulnerabilities, and disrupted access to services which were exacerbated by the pandemic • Social isolation may result in negative consequences for those with AUD, including serious withdrawal effects if alcohol is limited • Social isolation, financial pressures, and stress resulting from social distancing practices may lead to the initiation or exacerbation of addictive behaviors • In the United Kingdom (UK), alcohol sales had increased by 67% by March 2, 2020, while food increased by 43% • In the United States (US), total alcohol sales had increased by 34.2% the week of May 13, 2020 compared to the same week last year Finlay et al. BMJ 2020;369:1-2; Clay & Parker The Lancet 2020;5:e258-e259; Responsibility.org
What is “heavy drinking?” • Losing count? • Over a 6-pack of beer? • Over a case of beer? • When the bottle or glass of alcohol is too “heavy” to pick up any longer? The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines heavy drinking as 4 or more drinks in 2 hours for women, and 5 or more drinks in 2 hours for men.
Is this too much drinking?
Neurobiological Consequences of Heavy Drinking: MRI • 483 adolescents (ages 12–21) before initiation of drinking, and 1 and 2 years later • At 2 years: • 65 had initiated moderate drinking • 62 had initiated heavy drinking (1–10 drinks per occasion, several times weekly) • Heavy drinking group • Accelerated frontal cortical gray matter trajectory • Abnormal cortical volume: contributing factors include peak consumption in the past year and family history of alcoholism Pfefferbaum et al. American Journal of Psychiatry 2017 doi: 10.1176/appi.ajp.2017.17040469.
Effective Diagnostic Criteria DSM-IV DSM-5 Two distinct disorders, each with specific Integrates alcohol abuse and alcohol criteria: dependence into a single disorder called alcohol use disorder (AUD) Alcohol abuse Alcohol dependence Mild, moderate, and severe sub-classifications Abuse diagnosis: anyone meeting one or AUD diagnosis: anyone meeting any two of more of the “abuse” criteria (items one the eleven criteria during the same 12-month through four) within a 12-month period period Dependence diagnosis: anyone with three Severity based on number of criteria met or more of the “dependence” criteria (items five through eleven) during the same 12- month period Craving was added as a criterion for AUD Tyberski et al. AMS 2014;10(6):1191-7.
Effective Diagnostic Criteria: APA Guidelines • Initial psychiatric evaluation: assess misuse of any other substances, prescribed or otherwise • Include quantitative behavioral measures and biological markers to monitor alcohol use • Assess for co-occurring psychiatric conditions when selecting pharmacotherapy for AUD • Initial goals of treatment should: • Be agreed upon by patient and clinician, and documented in medical record • Involve discussion about patient’s legal obligations • Include discussion of risks to self and others from continued use of alcohol (e.g., impaired driving) Reus et al. AM J Psychiatry 2018;175(1):86-90.
Psychosocial Risk Factors Early-life Family history Parental psychopathy other Negative affect trauma/abuse of alcoholism than alcohol Hyperactivity to stress Poor executive functioning Deckel and Hesselbrock. Alcoholism: Clinical and Experimental Research 1996;20(7):1-6; Conrod et al. Alcoholism: Clinical and Experimental Research 1995;19(2):482-98.
Psychosocial Risk Factors (cont.) Deficits in emotional Conduct problems as Poor parenting reactivity/self early as preschool Adolescent risk factors: Academic Parental/peer Little parental Male delinquency/low substance using support competence Deckel and Hesselbrock. Alcoholism: Clinical and Experimental Research 1996;20(7):1-6; Conrod et al. Alcoholism: Clinical and Experimental Research 1995;19(2):482-98.
Childhood Trauma and Problem Alcohol Use • Prospective study from early childhood to adolescence • 1064 children and their parents in a longitudinal study • Baseline assessments at age 3–5 • At ages 12–14, self-reports, internalizing behavior, and drinking expectancies were obtained • At ages 18–20, drinking measures were assessed • Results: children living in homes with parental violence are more likely to use ineffective coping strategies such as using alcohol • Findings support the self-medication theory • Long-term effects of early-life experience on drinking behavior in adulthood Jester et al. Journal of Studies on Alcohol and Drugs 2015;76:781-9.
Genetic Contributions to AUD • Gene variants encoding several of the alcohol-metabolizing enzymes: alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence • Particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles have been associated with lower rates of alcohol dependence • The prevalence of these alleles differs among ethnic groups • Alleles interact to influence the risk of AUD • Environmental influences on these alleles that affect peoples’ alcohol involvement include: developmental stage, individual characteristics, and environmental factors
What About Dopamine? Genetic Variations and AUD In a recent review, the relationship between 56 genetic variants and 7 genes associated with the dopaminergic reward pathway and excessive alcohol consumption (EAC) were examined 880 Very low drinkers 653 heavy drinkers Single nucleotide polymorphisms Dopamine receptor D2 (SNPs) were genotyped Lifestyle factors assessed (DRD2) Rs10891556 only SNP positively DRD2 rs1800497 and rs877138 were Lifestyle factors associated with EAC correlated to alcohol significantly associated with EAC in men were predominantly men who consumption DRD2 rs17601612, DRD2 rs493627, smoked, consumed large amounts of and MAOA rs5906898 were associated meat, a low level of education, and with EAC in women low physical activity levels Celorrio et al. Alcohol and Alcoholism 2016;51(3):258-67.
Neurobiology: Actions of Alcohol on Reward Circuits Nucleus Accumbens (NA) alcohol VTA glu alcohol
Neurobiology: Detail of Alcohol Actions in the VTA arcuate PFC nucleus glu neuron opiate neuron opiate receptor MGlu receptor NMDA receptor VTA GABA-B receptor alcohol GABA-A receptor glu alcohol VSCC GABA VTA enkephalin DA neuron GABA DA inter- neuron alcohol
Pharmacological Treatment Options • Opioid antagonists: naltrexone, nalmefene • NMDA receptor/Ca2+ channels: acamprosate • Direct GABA B agonist: baclofen • GABA-activated chloride channel activation: topiramate • Topiramate is superior to nalmefene, naltrexone, and acamprosate on consumption outcomes, but its safety profile is known to be poor • Study concluded there is currently no high-grade evidence for pharmacological treatment for AUD, only low to medium efficacy in reducing drinking Palpacuer et al. Addiction 2017;113:220-37.
AUD "Pharmacy" gabapentin topiramate disulfiram second line naltrexone acamprosate first line CBT CET CST CAT nonpharmacological CST = communication skills training CBT = cognitive behavioral therapy CET = cue-elicited therapy AUD CAT = chemical aversion therapy pharmacy Reus et al. AM J Psychiatry 2018;175(1):86-90.
Naltrexone _ mu opiates
Actions of Naltrexone in the VTA: Reducing the Reward Associated With Drinking arcuate PFC nucleus glu neuron opiate neuron opiate receptor MGlu receptor NMDA receptor VTA GABA-B receptor naltrexone GABA-A receptor glu naltrexone VSCC GABA VTA enkephalin DA neuron GABA DA inter- neuron
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