Tratamento Farmacologico para Transtorno por Uso de Alcool - Revisao Medica

Alcohol use disorder Pharmacologic management AUTHOR Stephen R Holt MD MS FACP SECTION EDITOR Murray B Stein MD MPH DEPUTY EDITOR Michael Friedman MD All topics are updated as new evidence becomes available and our peer review process is complete Literature review current through Dec 2023 This topic last updated Dec 01 2023 INTRODUCTION Alcohol use disorders are among the most prevalent of all substance use disorders worldwide The single year prevalence globally has been estimated to be over 100 million individuals 1 Additionally nearly 3 million deaths 53 percent of all deaths globally have been attributed to alcohol in a single year 2 Most clinical trials of medication efficacy for alcohol use disorder studied recently abstinent individuals with an American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision DSMIVTR diagnosis of alcohol dependence Applying these findings to individuals diagnosed under the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition DSM5 is imprecise but the most closely comparable group of individuals are those with alcohol use disorder moderate to severe subtype ie individuals with four or more symptoms within a 12month period Pharmacologic treatment of alcohol use disorder has focused on altering the reinforcing effects of alcohol use Medication development has focused on several neurotransmitter systems that mediate reinforcement including opioid glutamate gammaaminobutyric acid and serotonin systems Several medications can be used to treat alcohol use disorder leading to reduced heavy drinking and increased days of abstinence 3 These outcomes likely reduce the overall risk associated with alcohol use disorder despite total abstinence not being achieved This topic reviews the pharmacotherapy for treatment of alcohol use disorder The epidemiology pathogenesis clinical manifestations assessment and diagnosis of risky drinking and alcohol use disorder as well as psychosocial treatments for the disorder are discussed separately Other topics related to alcohol use disorder including the management of withdrawal and nutritional issues are also reviewed separately See Risky drinking and alcohol use disorder Epidemiology clinical features adverse consequences screening and assessment See Screening for unhealthy use of alcohol and other drugs in primary care See Brief intervention for unhealthy alcohol and other drug use Efficacy adverse effects and administration See Alcohol withdrawal Ambulatory management See Management of moderate and severe alcohol withdrawal syndromes INDICATION FOR PHARMACOTHERAPY Medication treatment of alcohol use disorder has been shown to be effective in patients with moderate to severe subtypes of the disorder Medication should be prescribed in conjunction with psychosocial interventions though it should not be withheld if patients do not participate in or adhere to them See Alcohol use disorder Treatment overview section on Moderate or severe disorder In contrast medication treatment has not been extensively studied in patients with mild subtype of alcohol use disorder In these patients we suggest initial treatment with psychosocial interventions rather than with medication See Alcohol use disorder Treatment overview section on Mild disorder and Alcohol use disorder Psychosocial management An algorithm describes our approach to the pharmacologic management of alcohol use disorder algorithm 1 FIRSTLINE TREATMENT Suggested first and secondline agents used in the treatment of alcohol use disorder can be found on the associated table table 1 Naltrexone For most newly diagnosed patients with moderate or severe alcohol use disorder we suggest initial treatment with naltrexone Naltrexone is our preferred choice due to its preferable dosing schedule and the ability to begin treatment for alcohol use disorder while the individual is still drinking Naltrexone exerts its principal pharmacologic effects through blockade of the muopioid receptor Endogenous opioids modulate alcohols reinforcing effects 45 Naltrexone also modifies the hypothalamicpituitaryadrenal axis to suppress ethanol consumption 6 Contraindications Naltrexone should be avoided in individuals using opioids or prescribed opioids for pain management as well as in those with acute hepatitis or hepatic failure in such patients the alternative firstline treatment acamprosate is appropriate Formulations Naltrexone can be taken orally or administered in a longacting injectable LAI form Both oral and longacting dosing have demonstrated efficacy compared with placebo Comparative studies are limited and have come to different conclusions regarding comparative efficacy 79 LAI naltrexone For most patients treated with medication for alcohol use disorder the decision to begin oral versus intramuscular IM is based on patient preference We typically prefer starting IM naltrexone to ensure adherence However some may prefer to start with oral medication ie to see if side effects emerge or liver enzymes are affected before committing to a longer course of treatment Depot preparations of naltrexone may improve adherence by reducing the frequency of medication administration from daily to monthly However they do require an injection visit Some patients may adhere better to daily medication whereas others may be willing to attend monthly visits Additionally a steady state of medication level is achieved with LAI naltrexone This may avoid peak effects that might exacerbate adverse events 10 LAI naltrexone is given as an IM injection of 380 mg every four weeks to the gluteal area Common adverse events observed among individuals receiving LAI naltrexone included nausea 33 percent fatigue 20 percent and decreased appetite 13 percent The US Food and Drug Administration has reported 196 cases of serious injection site reactions from postmarketing surveillance including induration cellulitis hematoma abscess and necrosis Females appear to be at higher risk for this reaction Patients should report injectionsite pain swelling bruising pruritus or redness and seek medical attention if symptoms are not improving after one week Liver enzymes should be monitored within several weeks of initiating treatment and then every six months during ongoing treatment LAI naltrexone appears to be superior to placebo in reducing drinking and heavy drinking among adults with alcohol use disorder 1113 As examples In a metaanalysis individuals with alcohol use disorder treated with LAI naltrexone had fewer days of drinking per month compared with individuals receiving placebo five trials n 314 weighted mean difference 20 95 CI 339 to 061 12 Additionally individuals treated with LAI naltrexone had fewer heavy drinking days per month defined as four or more drinksday in females five or more drinksday in males than those in placebo group seven trials n 881 weighted mean difference 12 95 CI 21 to 023 In a subgroup analysis of a larger metaanalysis investigating treatment for alcohol use disorder while treatment with LAI naltrexone as compared with placebo was not associated with lower rates of return to drinking two trials n 939 or return to heavy drinking two trials n 615 it was associated with a greater reduction in percentage of drinking days two trials n 467 weighted mean difference 50 95 CI 95 to 05 and heavy drinking days three trials n 956 weighted mean difference 47 95 CI 86 to 073 as compared with placebo 13 Oral naltrexone Our practice is to start oral naltrexone at 50 mg per day and monitor for side effects While the usual dose of oral naltrexone is 50 mgday some trials have used up to 100 mgday 14 some also begin with 25 mg daily for several days and then increase the dose to 50 mg when the medication is tolerated well Trials generally have included efforts such as group and individual psychotherapy 15 Targeted as needed dosing may be a useful strategy for promoting adherence in young individuals who often prefer to take medication on an as needed basis 1617 While we typically prescribe naltrexone for daily use targeted dosing may be an effective alternative or supplement to daily dosing In one trial including 140 young adults with heavy drinking ie four or more heavy drinking days over the past four weeks the use of targeted naltrexone was found to reduce the likelihood of intoxication by nearly 23 percent versus placebo 16 Metaanalyses of clinical trials for alcohol dependence have found oral naltrexone to reduce alcohol consumption compared with placebo 131819 As examples In a metaanalysis of 50 randomized trials with 7793 subjects with alcohol use disorder naltrexone as compared with placebo reduced the risk of a return to heavy drinking 51 versus 61 percent relative risk 083 95 CI 076090 and decreased total drinking days by approximately 4 percent Any drinking was decreased by 5 percent 18 In a metaanalysis of trials of treatment for alcohol use disorder treatment with oral naltrexone 50 mg as compared with placebo was associated with decreased return to any drinking 16 trials n 2347 relative risk 093 95 CI 087099 decreased return to heavy drinking 23 trials n 3170 relative risk 081 95 CI 072 to 09 decreased percentage of drinking days 15 trials n 1992 weighted mean difference 51 CI 72 to 30 and percentage of heavy drinking days seven trials n 624 weighted mean difference 43 CI 76 to 09 13 Side effects of oral naltrexone are nausea headache and dizziness which subside with continued use Liver enzymes should be monitored within several weeks of initiating treatment and then every six months during ongoing treatment Fivefold elevation in liver enzymes occurred in 11 of 614 individuals who received naltrexone in the COMBINE study 14 Enzyme levels returned to baseline after discontinuation of medication in the nine individuals who had stopped drinking and returned for followup Elevations in liver enzymes are therefore largely attributable to heavy drinking in a large safety study 865 patients liver enzymes did not differ from a comparison group not taking naltrexone 20 Acamprosate Acamprosate is an effective alternative to naltrexone and is our first choice in patients with contraindications to naltrexone including those who are using opioids or prescribed opioids or in those with advanced liver disease For patients who have minimal to no response to naltrexone as first line of treatment we stop naltrexone and treat with acamprosate as our second choice unless contraindicated In individuals with a partial or insufficient response to naltrexone we augment with acamprosate however we do this less frequently as we are sensitive to avoiding polypharmacy Acamprosates principal antidrinking neurochemical effect has been attributed to the modulation of glutamate neurotransmission at metabotropic5 glutamate receptors 21 Contraindications Acamprosate is contraindicated in individuals with severe renal dysfunction creatinine clearance 30 mLmin Administration We begin treatment with acamprosate when abstinence is achieved and typically maintain treatment during return to use The usual dose for acamprosate is 666 mg three times daily However in individuals with moderate renal dysfunction creatinine clearance 30 to 50 mLmin an initial dose of 333 mg three times daily is recommended Additionally in individuals with a body weight 60 kg we typically initiate treatment at a lower dose eg 333 mg twice daily Efficacy Metaanalyses have shown that acamprosate is effective in maintaining abstinence in individuals with alcohol use disorder who were recently detoxified from alcohol use 132223 As httpswwwuptodatecomcontentsalcoholusedisorderpharmacologicmanagementprint 416 examples In a metaanalysis of 18 studies including nearly 2300 individuals who were recently detoxified from alcohol use acamprosate increased the likelihood of continuous abstinence versus placebo at 12 months odds ratio 186 95 CI 149233 23 In another metaanalysis investigating pharmacologic treatments for alcohol use disorder treatment with acamprosate as compared with placebo was associated with decreased return to any drinking 20 trials n 6380 relative risk 088 95 CI 083 to 093 and percentage of drinking days 14 trials n 4916 weighted mean difference 83 95 CI 122 to 44 13 Adverse effects The most prominent adverse events of treatment with acamprosate include diarrhea nervousness and fatigue These usually subside with continued use Because acamprosate is excreted mostly unchanged by the kidneys rather than the liver it can be used safely in alcoholdependent individuals with liver disease SPECIFIC PATIENT POPULATIONS A number of factors such as cooccurring disease patient motivation and treatment goals can influence the initial choice of medication for alcohol use disorder Patients with cooccurring hepatic disease In patients with acute hepatitis liver failure or in patients with liver enzymes 3 to 5 times normal we suggest initial treatment with acamprosate Naltrexone is contraindicated in these patients Patients with opioid use disorder For patients with alcohol use disorder with comorbid opioid use disorder but without other contraindications such as severe hepatic disease we use naltrexone to treat both conditions after a sufficient time has elapsed since opioid exposure see Opioid use disorder Pharmacologic management section on Naltrexone Opioid antagonist Naltrexone should be avoided in individuals currently using opioids Alternatively since opioid agonists are often the medication of choice for opioid use disorder the comorbid alcohol use disorder can be treated with acamprosate or other medications See Patients requiring additional therapy below Patients with clinically indicated opioid use For patients with alcohol use disorder who are taking prescribed opioid medication we suggest treatment with acamprosate rather than naltrexone Naltrexone an opioid antagonist cannot be given to patients needing to continue opioids eg for pain control or to treat opioid use disorder Pregnancy The treatment of pregnant women with substance use disorder should be managed by clinicians with specialized expertise in this area Psychosocial treatments are prioritized as there is a paucity of data on the safety of pharmacologic therapies for alcohol use disorder in pregnant individuals If abstinence is not achieved without the use of medications the risks of continued heavy drinking likely outweigh the possible adverse effects of medication In weighing risks and benefits of prospective treatment one should consider potentially harmful effects of alcohol to the mother and to the developing fetus with alcohol a known teratogen and the most common cause of congenital anomaly in httpswwwuptodatecomcontentsalcoholusedisorderpharmacologicmanagementprint 516 the United States One small study suggested no clear association between exposure to acamprosate with poor maternal or neonatal health outcomes 24 Acamprosate may also be favored because opioids may be desired around delivery However naltrexone has been used more widely for substance use disorder during pregnancy The American Psychiatric Association guidelines for the pharmacologic treatment of patients with alcohol use disorder state that for pregnant or breastfeeding women with alcohol use disorder pharmacologic treatments should not be used unless treating acute alcohol withdrawal or a cooccurring disorder 25 Topics related to substance use including alcohol use during pregnancy are reviewed separately 2627 See Substance use during pregnancy Screening and prenatal care and Alcohol intake and pregnancy Patients with nonabstinence goals We treat patients whose treatment goal is reduction of alcohol use with naltrexone as naltrexone can be initiated while the patients is still drinking Studies of acamprosate have generally enrolled patients who have abstained prior to starting medication PATIENTS REQUIRING ADDITIONAL THERAPY For individuals who have not responded adequately to either naltrexone or acamprosate we suggest the following therapeutic options Dose adjustments Trials have not supported using higher doses in individuals who have not responded sufficiently to initial therapy Despite this clinicians will often try a higher dose of medication if a lower dose does not reduce drinking sufficiently A plausible rationale for this practice is that a higher dose might compensate for missed doses Additionally a higher dose may have a greater perceived effect by an individual patient In one small study a higher level of betanaltrexone correlated with less alcohol craving 28 This may provide a rationale for using higher dose of naltrexone ie 100 mg in patients with persistent craving Subsequent medication trials There are limited empirical data supporting augmenting options for suboptimal response to initial medication in the treatment of alcohol use disorder Our practice is generally to switch from one medication to another in order to minimize polypharmacy See Combining medications below For patients who do not respond to naltrexone or acamprosate or if they are contraindicated our next choices are disulfiram or topiramate unless contraindicated We choose between these based on clinical presentation For example in patients who are motivated towards abstinence and in cases where significant social support is available we favor treatment with disulfiram In patients with a seizure disorder we favor topiramate table 1 Disulfiram Clinical trials suggest that disulfiram is effective principally when taken under supervised conditions Disulfiram is an aversive agent that does not directly influence motivation to drink but discourages drinking by causing an accumulation of alcohols primary metabolite acetaldehyde This accumulation causes unpleasant effects such as sweating headache dyspnea lowered blood pressure flushing sympathetic overactivity palpitations nausea and vomiting 29 httpswwwuptodatecomcontentsalcoholusedisorderpharmacologicmanagementprint 616 Administration Disulfiram is initially given at 250 to 500 mgday for one to two weeks followed by an average maintenance dose of 250 mgday with a range from 125 to 500 mg based on the severity of adverse effects Fortyeight hours of total abstinence is needed prior to starting disulfiram Patient education should address hidden forms of ethanol eg tonics and mouthwashes and also the duration of the drugs activity up to 14 days after stopping Supervised dosing is not required for this medication as highly motivated patients likely do not require this level of oversight Prior research however has suggested that patients who do have the benefit of supervised disulfiram dosing via strong social support tend to fare substantially better than controls with regards to sustained abstinence 30 Efficacy Several blinded randomized controlled trials have failed to demonstrate a treatment effect for disulfiram according to one metaanalysis 30 However investigators have argued that the unique deterrent effect of disulfiram necessitates openlabeled studies to investigate its efficacy 3032 Metaanalysis of 17 openlabeled studies found a medium to large treatment effect for disulfiram over controls which included both placebo and medication comparators naltrexone and acamprosate on abstinence outcomes Hedges g 07 95 CI 046093 30 However the ability to draw conclusions from this analysis is limited by substantial heterogeneity among trials in regard to patient populations measured outcomes and cotreatments in addition several studies were judged to have possible risk of bias Disulfiram reaction Reactions to disulfiram are selflimited However some individuals taking disulfiram who drink alcohol or alcoholcontaining products can have a severe reaction to the combination The severity and duration of the reaction depends on the amount of alcohol ingested The reaction may last for several hours or up to a day Individuals may present with symptoms such as chest pain confusion headache and vomiting that require further evaluation for myocardial infarction and other etiologies Once myocardial infarction is excluded in patients with chest pain treatment is primarily supportive antiemetics for vomiting Trendelenburg positioning and intravenous fluids for orthostatic hypotension diphenhydramine for flushing Fomepizole has been suggested for lifethreatening symptoms of acetaldehyde in patients with severe presentations Fomepizole 4methylpyrazole administered as a single intravenous 75 mgkg dose blocks alcohol dehydrogenase and has been shown to reverse disulfiram reactions in a small case series of patients with nonspecific electrocardiogram changes with chest pain who are unresponsive to fluid administration and norepinephrine 3334 Contraindications Contraindications to disulfiram include clinically significant coronary artery disease psychosis and known hypersensitivity to the medication or other thiuram derivatives 3536 Adverse effects Side effects of disulfiram are usually minor including fatigue mild drowsiness headache and dermatitis Severe adverse reactions are rare but include psychosis and hepatitis Individuals receiving disulfiram should be monitored for hepatotoxicity several weeks after initiating treatment and then every six months if treatment with disulfiram continues 37 Topiramate Topiramate is our preferred choice of medications in patients who have a seizure disorder that would be appropriately treated with it and who have failed initial treatment with naltrexone or acamprosate Topiramate an anticonvulsant medication with pharmacological properties including blocking of voltagedependent sodium channels potentiation of gammaaminobutyric acid mediated transmission and antagonism of glutamate receptors has been found to decrease alcohol use in individuals with alcohol use disorder Administration Topiramate is initiated at a dose of 25 mg daily and can be slowly titrated up to a maximum dose of 300 mgday over eight weeks A titration schedule is shown in the table table 2 Efficacy In clinical trials topiramate reduces alcohol consumption compared with placebo 183839 A metaanalysis of seven clinical placebocontrolled trials with a total of 1125 individuals with alcohol dependence demonstrated efficacy for topiramate with higher rates of abstinence and lower rates of heavy drinking but similar measure of alcohol craving 38 The specific outcome measures used varied across studies but overall the effects were judged to be small to moderate Adverse effects Adverse effects associated with topiramate include cognitive impairment eg wordfinding difficulties paresthesias weight loss headache fatigue dizziness and depression Many of these are intolerable to a relatively small but significant proportion of individuals See Antiseizure medications Mechanism of action pharmacology and adverse effects section on Topiramate Gabapentin Gabapentin may be a reasonable option for patients who may have previously failed a firstline option particularly if gabapentin was used during a successful ambulatory detoxification Clinical trials testing the efficacy of gabapentin at various doses from 900 to 3600 mg have found mixed results in treatment for alcohol use disorder 4042 In a metaanalysis of seven placebocontrolled randomized controlled trials gabapentin was effective only on a single drinking outcome percent of heavy drinking days g 064 95 CI 006122 43 In one small trial the efficacy of gabapentin in reducing heavy drinking appeared more pronounced in those with withdrawal symptoms compared with those without 42 See Alcohol withdrawal Ambulatory management section on Very mild withdrawal CIWAAr 10 One important risk of gabapentin is its addictive potential Combining medications Combining medications in the treatment of alcohol use disorder has not been supported by trials Theoretically the combination of medications with different mechanisms of action offers the possibility of more effective treatment for patients who do not respond adequately to an individual agent As an example if some effect is achieved with naltrexone adding acamprosate could have added effect in an individual However randomized clinical trials have thus far not found medication combinations naltrexoneacamprosate 14 and naltrexonesertraline 4445 to be more effective than the individual medications In most cases our practice is to switch from agent to another rather than adding a second agent Agents with limited empirical support Other medications with few data to support their use are discussed briefly below Due to limited empirical support in the treatment of alcohol use disorder we cannot recommend them as first or secondline agents until further studies support their efficacy Nalmefene Nalmefene an opioid antagonist has been found to reduce drinking in individuals with alcohol use disorder using a targeted dosing strategy however the methodological rigor of the trials have been questioned 4647 Nalmefene has several potential advantages over naltrexone including absence of dosedependent liver toxicity longeracting effects and more effective binding to central opiate receptors Nalmefene is approved for treatment of alcohol use disorder in the European Union It is available in the United States as treatment for opioid overdose 184851 Selective serotonin reuptake inhibitors SSRIs Preliminary evidence suggests that subtypes of alcohol dependence may respond differently to serotonergic drugs with more favorable outcomes seen in the group characterized by a later age of onset less psychosocial morbidity and low familial loading Additionally SSRIs may be useful in treating individuals with depression and substance use disorder commonly occurring comorbidities 5255 Ondansetron This is a serotonin 5HT3 receptor antagonist used to treat chemotherapyinduced nausea Ondansetron may be selectively efficacious in individuals with earlyonset subtype of alcohol dependence onset of problem drinking prior to age 25 years and in individuals with family history of alcohol use disorder 5658 Varenicline While an earlier study reported on the potential for varenicline to reduce alcohol consumption in individuals with alcohol use disorder 59 this effect might be more limited 60 and in need of further validation Some studies suggest that varenicline treatment may be associated with reduced drinking in patients with alcohol addiction who smoke and in patients with alcohol use disorder and depression 6162 Psilocybin Psilocybin administered in combination with psychotherapy appears to decrease the number of heavy drinking days in individuals with alcohol use disorder In a trial 95 subjects with alcohol use disorder were randomly assigned to two daylong medication sessions week 4 and week 8 with psilocybin or diphenhydramine active control each in addition to 12 weeks of manualized psychotherapy 63 Over the 32week followup period subjects in the psilocybin group reported a lower percentage of heavy drinking days than those in the diphenhydramine group 97 versus 236 respectively mean difference 1386 95 CI 30247 Furthermore subjects in the psilocybin group had fewer mean drinks per day than the diphenhydramine group 12 versus 23 respectively mean difference 11 95 CI 027092 No serious adverse events were reported among either group Although psilocybin is classified as a Schedule I controlled substance in the United States no accepted medical use and high potential for abuse these data suggest that further evaluation of psilocybin for alcohol use disorder management may be warranted Others Baclofen 6465 prazosin and doxazosin alpha1 antagonists 66 also have limited data to support their use Alcohol use disorder Pharmacologic management UpToDate For patients who are pregnant we prefer psychosocial treatments as there is a paucity of data on the safety of pharmacologic therapies for alcohol use disorder See Pregnancy above For patients whose goal is reduction of alcohol use rather than abstinence we prefer naltrexone See Patients with nonabstinence goals above Subsequent medication trials There are limited empirical data supporting augmenting options for suboptimal response to initial medication in the treatment of alcohol use disorder Our practice is generally to switch from one medication to another in order to minimize polypharmacy See Subsequent medication trials above For patients who do not respond to naltrexone or acamprosate or if they are contraindicated our next choices are disulfiram or topiramate unless contraindicated See Disulfiram above and Topiramate above Other medication options with limited data supporting their use include gabapentin selective serotonin reuptake inhibitors ondansetron and varenicline We reserve their use for refractory cases See Agents with limited empirical support above ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Bankole A Johnson DSc MD MBChB MPhil FRCPsych DFAPA who contributed to an earlier version of this topic review REFERENCES 1 GBD 2016 Alcohol and Drug Use Collaborators The global burden of disease attributable to alcohol and drug use in 195 countries and territories 19902016 a systematic analysis for the Global Burden of Disease Study 2016 Lancet Psychiatry 2018 5987 2 World Health Organization WHO Global status report on health and alcohol 2018 3 Ernst DB Pettinati HM Weiss RD et al An intervention for treating alcohol dependence relating elements of Medical Management to patient outcomes with implications for primary care Ann Fam Med 2008 6435 4 Lee YK Park SW Kim YK et al Effects of naltrexone on the ethanolinduced changes in the rat central dopaminergic system Alcohol Alcohol 2005 40297 5 Hemby SE Johnson BA Dworkin SI Neurobiological basis of drug reinforcement In Drug Addiction and Its Treatment Nexus of Neuroscience and Behavior Johnson BA Roache JD Eds LippincottRa ven Philadelphia 1997 p137 6 Williams KL Broadbear JH Woods JH Noncontingent and responsecontingent intravenous ethanol attenuates the effect of naltrexone on hypothalamicpituitaryadrenal activity in rhesus monkeys Alcohol Clin Exp Res 2004 28566 7 Hartung DM McCarty D Fu R et al Extendedrelease naltrexone for alcohol and opioid dependence a metaanalysis of healthcare utilization studies J Subst Abuse Treat 2014 47113 8 CritsChristoph P Markell HM Gibbons MB et al A Naturalistic Evaluation of ExtendedRelease Naltrexone in Clinical Practice in Missouri J Subst Abuse Treat 2016 7050 httpswwwuptodatecomcontentsalcoholusedisorderpharmacologicmanagementprint 1116 Links to society and governmentsponsored guidelines from selected countries and regions around the world are provided separately See Society guideline links Alcohol use disorders and withdrawal INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials The Basics and Beyond the Basics The Basics patient education pieces are written in plain language at the 5th to 6th grade reading level and they answer the four or five key questions a patient might have about a given condition These articles are best for patients who want a general overview and who prefer short easytoread materials Beyond the Basics patient education pieces are longer more sophisticated and more detailed These articles are written at the 10th to 12th grade reading level and are best for patients who want indepth information and are comfortable with some medical jargon Here are the patient education articles that are relevant to this topic We encourage you to print or email these topics to your patients You can also locate patient education articles on a variety of individuals by searching on patient info and the keywords of interest Basics topic see Patient education Alcohol use when is drinking a problem The Basics Beyond the Basics topic see Patient education Alcohol use when is drinking a problem Beyond the Basics SUMMARY AND RECOMMENDATIONS Indications for pharmacotherapy We prefer to treat individuals with moderate or severe alcohol use disorder with pharmacotherapy in conjunction with psychosocial intervention However for individuals with the mild subtype of the disorder we prefer to begin with psychosocial intervention only algorithm 1 See Indication for pharmacotherapy above Firstline treatment For most patients treated with medication for moderate or severe alcohol use disorder we suggest initial treatment with naltrexone versus other medications available Grade 2C Naltrexone is preferred because of its once daily dosing and the ability to begin treatment while the individual is still drinking See Naltrexone above Acamprosate is an appropriate alternative to naltrexone for initial therapy and is our firstchoice treatment for individuals who are using opioids or prescribed opioids as well as in those with advanced liver disease See Acamprosate above and Patients with cooccurring hepatic disease above For specific 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Psilocybin Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder A Randomized Clinical Trial JAMA Psychiatry 2022 79953 64 Rose AK Jones A Baclofen its effectiveness in reducing harmful drinking craving and negative mood A metaanalysis Addiction 2018 1131396 65 Bschor T Henssler J Müller M Baethge C Baclofen for alcohol use disordera systematic meta analysis Acta Psychiatr Scand 2018 138232 66 Vanderkam P Solinas M Ingrand I et al Effectiveness of drugs acting on adrenergic receptors in the treatment for tobacco or alcohol use disorders systematic review and metaanalysis Addiction 2021 1161011 Disclaimer This generalized information is a limited summary of diagnosis treatment andor medication information It is not meant to be comprehensive and should be used as a tool to help the user understand andor assess potential diagnostic and treatment options It does NOT include all information about conditions treatments medications side effects or 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