Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings.

The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol dependence.

The US Food and Drug Administration (FDA)-approved medications naltrexone and acamprosate have shown mixed results in clinical trials.

Oral naltrexone and naltrexone depot formulations have generally demonstrated efficacy at treating alcohol dependence, but their treatment effect size is small, and more research is needed to compare the effects of different doses on drinking outcome.

Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. In U.S. trials, acamprosate has not proved to be efficacious.

Research continues to explore which types of alcohol-dependent individual would benefit the most from treatment with naltrexone or acamprosate.

The combination of the two medications demonstrated efficacy for treating alcohol dependence in one European study but not in a multi-site U.S. study.

Another US FDA-approved medication, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram is most effective when given to those who are highly compliant or who are receiving their medication under supervision.

Of the non-approved medications, topiramate is among the most promising, with a medium effect size in clinical trials.

Another promising medication, baclofen, has shown efficacy in small trials.

Serotonergic agents such as selective serotonin reuptake inhibitors and the serotonin-3 receptor antagonist, ondansetron, appear to be efficacious only among certain genetic subtypes of alcoholic.

As neuroscientific research progresses, other promising medications, as well as medication combinations, for treating alcohol dependence continue to be explored.

Research; Johnson BA. Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings. Biochem Pharmacol. 2007 Aug 9;

Brief-TSF is an excellent psychosocial adjunctive therapy with anticraving medications.

In a new target population researchers have found that alcoholics who have a particular variant of an opioid-receptor gene appear to respond better to naltrexone, an opioid antagonist that is used to reduce alcohol craving and relapse.

National Institute on Alcohol Abuse and Alcoholism (NIAAA) researchers who reviewed data from the 2001-2004 COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) study found that 87 percent of patients with the OPRM1 gene variant reported good outcomes with naltrexone treatment, compared to 49 percent of those receiving placebos and 55 percent of individuals lacking the gene variant who received either a placebo or naltrexone.

The study defined good outcomes as abstinence or moderate alcohol consumption without attendant problems.

“Analysis of the large COMBINE patient population increases confidence that the OPRM1 variant is in part responsible for positive responses to naltrexone,” said Ting-Kai Li, director of NIAAA. “This study points to the promise of research on gene-medication interactions to refine treatment selection, improve clinical results, and inform ongoing medications development.”

The research was published in the Feb. 4, 2008 issue of the Archives of General Psychiatry.

See also;

• Brief-TSF can assist patients cease alcohol consumption.
• Anti-craving Naltrexone Injection Reduces Drinking

The Role of Uncontrollable Trauma in the Development of PTSD and Alcohol Addiction

By Joseph Volpicelli, M.D., Ph.D.; Geetha Balaraman; Julie Hahn; Heather Wallace, M.A.; and Donald Bux, Ph.D.

After a traumatic event, people often report using alcohol to relieve their symptoms of anxiety, irritability, and depression.

Alcohol may relieve these symptoms because drinking compensates for deficiencies in endorphin activity following a traumatic experience. Within minutes of exposure to a traumatic event there is an increase in the level of endorphins in the brain.

During the time of the trauma, endorphin levels remain elevated and help numb the emotional and physical pain of the trauma.

However, after the trauma is over, endorphin levels gradually decrease and this may lead to a period of endorphin withdrawal that can last from hours to days. This period of endorphin withdrawal may produce emotional distress and contribute to other symptoms of posttraumatic stress disorder (PTSD).

Because alcohol use increases endorphin activity, drinking following trauma may be used to compensate this endorphin withdrawal and thus avoid the associated emotional distress. This model has important implications for the treatment of PTSD and alcoholism.

Alcohol Research & Health, Vol. 23, No. 4, 1999

Alcohol dependence is a chronic, relapsing bio-behavioral disease mediated by various parts of the brain, including reward systems, memory circuits, and the prefrontal cortex.

It is characterized by loss of the ability to drink alcohol in moderation and continued drinking despite negative consequences.

The alcohol withdrawal syndrome is a common but not universal diagnostic feature of alcohol dependence.

Benzodiazepine assisted detoxification of the alcohol withdrawal syndrome prevents the development of withdrawal seizures and delirium tremens, and makes patients more comfortable, which promotes engagement in treatment.

Symptom-triggered dosing, based on a withdrawal rating scale such as the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised, is optimal for minimizing the total benzodiazepine dosage.

Use of a long-acting benzodiazepine (eg, chlordiazepoxide) is preferred in uncomplicated patients.

Thiamine should be administered routinely before the administration of intravenous fluids to prevent the development of Wernicke’s encephalopathy and Wernicke-Korsakoff syndrome.

In combination with psychosocial treatment naltrexone, and acamprosate can reduce the frequency of relapse.

Naltrexone may be more effective for reduction of loss of control with the first drink and cue-related craving.

Acamprosate may be more effective for stabilizing the physiology of post-acute withdrawal.

Psychiatric co-morbidity, especially depression, is common and is best addressed concurrently, although definitive diagnosis may have to await a period of prolonged sobriety.

Prescription of addictive substances, including benzodiazepines beyond the period of acute detoxification, should be avoided, and if necessary should be closely monitored (eg, by frequent visits with small prescriptions or clinic administed, and/or urine or breath alcohol screenings).

Abstinence from alcohol is recommended for persons with alcohol dependence.

Psychosocial treatment and participation in Alcoholics Anonymous can help patients achieve and maintain abstinence.

Research report; The psychiatric management of patients with alcohol dependence. Curr Treat Options Neurol. 2007 Sep;9(5):381-92. Ritvo JI, Park C.

Brief-TSF training is designed to complement this model.

Mechanisms of behavior change in alcoholics anonymous: does Alcoholics Anonymous lead to better alcohol use outcomes by reducing depression symptoms?

Rationale  Indices of negative affect, such as depression, have been implicated in stress-induced pathways to alcohol relapse. Empirically supported continuing care resources, such as Alcoholics Anonymous (AA), emphasize reducing negative affect to reduce relapse risk, but little research has been conducted to examine putative affective mechanisms of AA’s effects.

Methods  Using lagged, controlled, hierarchical linear modelling and meditational analyses this study investigated whether AA participation mobilized changes in depression symptoms and whether such changes explained subsequent reductions in alcohol use. Alcohol-dependent adults (n = 1706), receiving treatment as part of a clinical trial, were assessed at intake, 3, 6, 9, 12 and 15 months.

Results  Findings revealed elevated levels of depression compared to the general population, which decreased during treatment and then remained stable over follow-up. Greater AA attendance was associated with better subsequent alcohol use outcomes and decreased depression. Greater depression was associated with heavier and more frequent drinking. Lagged mediation analyses revealed that the effects of AA on alcohol use was mediated partially by reductions in depression symptoms. However, this salutary effect on depression itself appeared to be explained by AA’s proximal effect on reducing concurrent drinking.

Conclusions  AA attendance was associated both concurrently and predictively with improved alcohol outcomes. Although AA attendance was associated additionally with subsequent improvements in depression, it did not predict such improvements over and above concurrent alcohol use. AA appears to lead both to improvements in alcohol use and psychological and emotional wellbeing which, in turn, may reinforce further abstinence and recovery-related change.

Research; John F. Kelly, Robert L. Stout, Molly Magill, J. Scott Tonigan & Maria E. Pagano, Addiction, Volume 105 Issue 4, Pages 626 – 636

• See also
• Disturbing Denial
• Strategies for Dealing With Denial
• Addiction & Recovery Books
• The Dual Disorders Recovery Book
• Acceptance and Surrender

Alcoholics Anonymous and long term matching effects.

AIMS: (1) To examine the matching hypothesis that Twelve Step Facilitation Therapy (TSF) is more effective than Motivational Enhancement Therapy (MET) for alcohol-dependent clients with networks highly supportive of drinking 3 years following treatment; (2) to test a causal chain providing the rationale for this effect. DESIGN: Outpatients were re-interviewed 3 years following treatment. ANCOVAs tested the matching hypothesis. SETTING: Outpatients from five clinical research units distributed across the United States. Participants: Eight hundred and six alcohol-dependent clients. INTERVENTION: Clients were randomly assigned to one of three 12-week, manually-guided, individual treatments: TSF, MET or Cognitive Behavioral Coping Skills Therapy (CBT). MEASUREMENTS: Network support for drinking prior to treatment, Alcoholics Anonymous (AA) involvement during and following treatment, percentage of days abstinent and drinks per drinking day during months 37-39.

FINDINGS:

• The a priori matching hypothesis that TSF is more effective than MET for clients with networks supportive of drinking was supported at the 3 year follow-up;
• AA involvement was a partial mediator of this effect; clients with networks supportive of drinking assigned to TSF were more likely to be involved in AA;
• AA involvement was associated with better 3-year drinking outcomes for such clients.

CONCLUSIONS:

• in the long-term TSF may be the treatment of choice for alcohol-dependent clients with networks supportive of drinking;
• involvement in AA should be given special consideration for clients with networks supportive of drinking, irrespective of the therapy they will receive.

Research; Longabaugh R, Wirtz PW, Zweben A, Stout RL. Network support for drinking, Alcoholics Anonymous and long-term matching effects.Addiction. 1998 Sep;93(9):1313-33.

AA and 12 step alcoholism treatment programs

The author of this report notes that AA self-help groups are the most commonly accessed component of treatment for alcoholism and alcohol-related problems. Additionally, the concepts and approaches of AA have significantly influenced other twelve-step programs in professional treatment.

Research has indicated that participation in AA or other 12-step programs results in reductions in substance abuse and also in psychiatric problems, reducing health care costs over time.

Section headings in this book chapter include:

1. nature and prevalence of AA;
2. nature and prevalence of 12-step treatment programs;
3. evaluations of community-based AA groups;
4. evaluation research on 12-step oriented professional treatment programs
5. potential future research directions.

Research report; Humphreys, K. Alcoholics Anonymous and 12-step alcoholism treatment programs. In: M. Galanter, Ed., Recent Developments in Alcoholism: Volume 16. Research on Alcoholism Treatment, New York, NY: Kluwer Academic/Plenum Publishers, 2003. (pp. 149-164)

Cost-Effectiveness of Home Visits in the Outpatient Treatment of Patients with Alcohol Dependence

The purpose of this study was to compare the cost-effectiveness of conventional outpatient treatment for alcoholic patients (CT) with this same conventional treatment plus home visits (HV), a new proposal for intervention within the Brazilian outpatient treatment system.

A cost-effectiveness evaluation alongside a 12-week randomized clinical trial was performed. We identified the resources utilized by each intervention, as well as the cost according to National Health System (SUS), Brazilian Medical Association (AMB) tables of fees, and others based on 2005 data. The incremental cost-effectiveness ratio (ICER) was estimated as the main outcome measure – abstinent cases at the end of treatment.

• There were 51.8% abstinent cases for HV and 43.1% for CT, a clinically relevant finding.
• Other outcome measures, such as quality of life, also showed significant improvements that favored HV.

The baseline scenario presented an ICER of USD 1,852. Sensitivity analysis showed an ICER of USD 689 (scenario favoring HV) and USD 2,334 (scenario favoring CT).

The HV treatment was found to be cost-effective according to the WHO Commission on Macroeconomics and Health.

Research; Edilaine Moraesa, Geraldo M. Camposa, Neliana B. Figliea, Ronaldo Laranjeiraa, Marcos B. Ferrazb. Eur Addict Res 2010;16:69-77 (DOI: 10.1159/000268107)

• See also
• Psychology Books
• 12 Steps and Post Traumatic Stress
• AA & NA Work for Teens Too
• Stools and Bottles
• Brief-TSF can assist patients cease alcohol consumption.

Biomarkers in Alcohol Misuse: Their Role in the Prevention and Detection of Thiamine Deficiency

In Western countries alcohol misuse is the most frequent cause of thiamine (vitamin B1) deficiency (TD) and consequent neuro-impairment.

Studies have demonstrated that between 30 and 80% of alcoholics are thiamine deficient, and this puts them at risk of developing the Wernicke–Korsakoff (WK) syndrome.

The relative roles of alcohol and TD in causing brain damage remain controversial and it is important to try to determine the role played by each factor.

Animal studies support an additive effect of alcohol exposure and TD, and indicate the potential for interaction between alcohol and TD in human alcohol-related brain damage.

Early diagnosis of alcohol-related TD is therefore an important aspect of effective intervention and treatment.

Alcohol biomarkers provide a direct and indirect way of estimating the amount of alcohol being consumed, the duration of ingestion and the harmful effects that long-term alcohol use has on body functions.

Appropriate use of these markers is very helpful when considering a diagnosis of alcohol-related TD.

Research report; Rosanna Mancinelli, and Mauro Ceccanti. Biomarkers in Alcohol Misuse: Their Role in the Prevention and Detection of Thiamine Deficiency. Alcohol and Alcoholism 2009 44(2):177-182;

See also;

• 12-Step Treatment More Effective than Alternative
• AA Offers Recovery Not Religion
• AA and Treatment Work Better Together

I’ll Quit Tomorrow: A Practical Guide to Alcoholism Treatment

The Alcohol Use Disorders Identification Test (AUDIT) as screening instrument for adolescents.

BACKGROUND: The Alcohol Use Disorders Identification Test (AUDIT) is an international screening instrument extensively employed in adult target groups. However, there is scarce information on screening with the AUDIT in adolescent populations.

The purpose of this study was to determine the cut-off point for hazardous, harmful, and dependent alcohol use through the validation of the AUDIT in a Chilean adolescent sample.

METHODS: The original English version of the AUDIT was translated into Spanish, using the procedure recommended by the World Health Organization. The text was then back-translated and sent to one of the original authors (Thomas Babor), who approved the translation. Students attending public schools in Santiago, Chile, self-administered the AUDIT, and those older than 15 years completed the

Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM), which served as a gold standard. Between 1 and 4 weeks after the CIDI-SAM, participants answered a second AUDIT.

RESULTS:

• A total of 42 female and 53 male adolescents (mean age: 15.9 [SD=1.2]) completed the AUDIT, with a mean score of 4.3.
• Reliability according to Cronbach’s alpha was 0.83.
• Test-retest correlation was also satisfactory (intra-class correlation 0.81 [95% CI 0.73-0.87]).
• Analysis of the receiver operating characteristic (ROC) curve yielded cut-off points for hazardous, harmful, and dependent alcohol use of 3, 5, and 7 points, respectively.

CONCLUSIONS: The Chilean version of the AUDIT is a valid and reliable tool for identifying adolescents with hazardous, harmful, and dependent alcohol use. The suggested cut-off points make screening with the AUDIT more accurate for adolescent populations.

Research; Drug Alcohol Depend. 2009 Aug 1;103(3):155-8. Epub 2009 May 6. The Alcohol Use Disorders Identification Test (AUDIT) as a screening instrument for adolescents. Santis R, Garmendia ML, Acuña G, Alvarado ME, Arteaga O.

• See also;
• 12-Step Treatment More Effective than Alternative
• Brief-TSF ASSESSMENT
• Brief-TSF can assist patients cease alcohol consumption.
• Learn about the disease

Youth With Alcohol and Drug Addiction: Escape from Bondage (Helping Youth With Mental, Physical, and Social Challenges) by Kenneth McIntosh

Different Like Me: A Book for Teens Who Worry About Their Parent’s Use of Alcohol/Drugs by Evelyn Leite