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KaarloSimojoki

Drugs Used in Alcohol Dependence

Essentials

  • Alcohol dependence is a chronic illness the prognosis of which may be improved with drug therapy.
  • Psychosocial therapies without combination with drug therapy provide moderate effect in mild or moderate alcohol dependence. Continuity of care and good therapeutic relationship are essential.
  • Supervised medication with naltrexone Naltrexone for Alcohol Dependence, disulfiram Disulfiram for Alcohol Dependence or acamprosate Acamprosate for Alcohol Dependence, when combined with psychosocial therapies will improve therapy outcomes.
  • Counselling that supports reduction of alcohol consumption and that is combined with nalmefene medication Nalmefene for Alcohol Dependence reduces alcohol intake in persons with mild to moderate alcohol dependence.
  • The best results have been achieved by combining pharmacological agents with therapy aimed at controlling alcohol use and preventing relapses and with family and network therapies. Treatment methods applying the cognitive framework have been proven effective.
  • The possibility to provide therapy with naltrexone, disulfiram and acamprosate should be available in all healthcare services. Other medications or medication combinations are best suited for use primarily in units specializing in the care of alcohol and drug abusers.

Naltrexone and nalmefene

  • Addiction is considered as a dysfunction of the reward-regulating centres within the central nervous system. The alcohol-induced euphoria can be reduced by opioid antagonists.

Dose of naltrexone

  • The recommended daily dose of naltrexone is 50 mg. Because of variable bioavailability, the dose may vary from 25 mg to 100 mg according to the clinical response.
  • Combined with psychosocial therapy, naltrexone will increase the amount of abstinence days and reduce the amount of relapses Naltrexone for Alcohol Dependence. It may also reduce relapses when directed to situations that are associated with increased risk of relapse.
  • To induce abstinence the initial treatment period should be uninterrupted and of sufficient duration.

Follow-up of naltrexone

  • Naltrexone may cause disturbances in hepatic function, and plasma aminotransferase concentrations should be checked every 2-3 weeks in the initiation phase of the therapy. After the first 3 months, the follow-up tests should be performed every 6 months.

Dose of nalmefene

  • NalmefeneNalmefene for Alcohol Dependence is recommended for patients with alcohol dependence in whom alcohol intake poses a high health risk, who have no physical withdrawal symptoms and who are not in need of immediate detoxification.
  • The key goal is a reduction in the number of drinking times and/or amount of alcohol consumed per drinking time.
  • The tablet should be taken 1 to 2 hours before the intended drinking occasion or immediately after the drinking has started.
  • Dose per 24 hours is 18 mg.

Follow-up of nalmefene

  • Plasma ALT and gamma-glutamyl transferase (GGT) concentrations are determined before the medication is started. Caution is required if the concentrations are more than 3 times the upper limit of the reference range.
  • The only contraindication is severe liver failure.
  • Recheck of the liver function tests may be useful to follow up the effectiveness of the treatment.
  • Total abstinence from alcohol should be recommended to the patient if adverse effects of drinking continue even with the medication.

Disulfiram

  • Disulfiram inhibits the enzyme aldehyde dehydrogenase. The inhibition gives rise to the accumulation of acetaldehyde in the body after ingestion of alcohol. Aceltadehyde causes very unpleasant systemic reactions (an "Antabuse reaction"), the fear of which stops the person from ingesting alcohol.
    • The symptoms include: flushing of the face, hypotension, reflectory tachycardia, palpitations, anxiety, headache, nausea and vomiting.
  • Disulfiram is used to support a so-called brief intervention Brief Interventions for Risky Use of Alcohol and to prevent impulsive relapses in motivated patients, who have undergone successful detoxification Disulfiram for Alcohol Dependence.
  • Supervised disulfiram medication significantly improves the results achieved with psychosocial therapies alone.

Dose

  • Supervised oral administration which can be carried out, if possible, also with the support of the patient's close ones.
  • The treatment is started with a dose of 800 mg on 3 consecutive days. Thereafter the dose is 400 mg twice a week or (100-)200 mg daily.
  • Even small amounts of alcohol may precipitate a reaction up to 2 weeks after the last dose.
  • If the above-mentioned doses are insufficient to induce a reaction, the dose can be doubled.
  • The medication should be taken for 6-12 months. During this period the risk of relapse diminishes. If the patient did relapse, disulfiram can be introduced again.
  • Subcutaneous disulfiram implants are ineffective.

Follow-up

  • Liver enzymes (plasma ALT and gamma-GT) should be checked before the treatment is introduced and every two weeks thereafter for two months.
  • Laboratory markers such as gamma-GT, MCV and CDT, should be checked e.g. every 3-6 months. Favourable changes in the markers support abstinence.
  • Disulfiram may induce liver damage 2-3 months after treatment onset. The liver damage will not become chronic upon discontinuation of treatment, but in rare cases it may be fatal.
  • Close monitoring is important at the beginning of the treatment due to possible neurological and psychiatric adverse effects as well as cutaneous eruptions.
  • Disulfiram has interactions with phenytoin, theophylline and warfarin. The dose of these drugs should be adjusted accordingly.
  • The concomitant use of metronidazole, isoniazid and amitriptyline can induce confusion which may lead to psychosis.

Acamprosate

  • Affects the excitatory glutaminergic neural system in the brain and acts as an antagonist to the GABA receptors. It is supposed to reduce craving for alcohol.
  • Suited for support of therapy in severe or moderately severe alcohol dependence when the aim is to remain abstinent.

Dose

  • The recommended dose is 2 tablets (à 333 mg) 3 times a day regularly.
  • Special national regulations may apply concerning prescription of acamprosate.
  • The medication is started immediately after detoxification and it should last at least for one year.

Adverse effects and contraindications

  • The reported adverse effects have been minor; diarrhoea is the most common one. Other adverse effects include dyspepsia, nausea, vomiting and itching.
  • The drug is not recommended during pregnancy or breast-feeding. The drug is contraindicated in severe renal or hepatic insufficiency.
  • Interactions have so far been studied only little. No harmful interactions have been observed with disulfiram or naltrexone, and neither with benzodiazepines or with antidepressant or hypnotic drugs.

Other drugs

  • Selective serotonin re-uptake inhibitors (SSRIs) do not improve the outcomes achieved with psychosocial therapy in the treatment of alcohol dependence.
    • 30% to 60% of alcoholics have a clinically significant depression and antidepressants probably reduce symptoms of depression in depressed persons with a drink problem.
    • Problem drinking is often intertwined with mental health problems, and co-operation with specialized psychiatric care may be necessary (especially in psychotic disorders).
  • Hypnotic drugs are shown to be effective only in short-term use. Drug therapy for anxiety (SSRIs, possibly buspirone) appears to reduce anxiety symptoms in persons with a drink problem.
  • Nitrous oxide is ineffective in the treatment of alcoholism. Acupuncture does not improve the effect of therapy, but momentarily relieves mild symptoms that the patient experiences.

Drugs with less experience of useBaclofen for Alcohol Use Disorder, Oral Topiramate for Alcohol Dependence

  • Topiramate is an antiepileptic drug that may reduce the pleasurable effects of alcohol and thus help controlling alcohol use Oral Topiramate for Alcohol Dependence.
  • Quetiapine may reduce alcohol consumption for instance in special groups, such as in persons with bipolar disorder who have become alcoholics.
  • Ondansetron (an antiemetic) is a serotonin 5-HT3 receptor antagonist. It may reduce alcohol use and seems to be effective particularly in the treatment of persons who have become alcoholics at a young age.
  • Baclofen is a GABA-B receptor antagonist that reduces spasticity of skeletal muscles. It may increase the success rate of abstinence achieved by psychosocial treatment Baclofen for Alcohol Use Disorder in alcoholics with cirrhosis.

References

  • Gual A, He Y, Torup L et al. A randomised, double-blind, placebo-controlled, efficacy study of nalmefene, as-needed use, in patients with alcohol dependence. Eur Neuropsychopharmacol 2013;23(11):1432-42. [PubMed]
  • Mann K, Bladström A, Torup L et al. Extending the treatment options in alcohol dependence: a randomized controlled study of as-needed nalmefene. Biol Psychiatry 2013;73(8):706-13. [PubMed]
  • Aubin HJ, Daeppen JB. Emerging pharmacotherapies for alcohol dependence: a systematic review focusing on reduction in consumption. Drug Alcohol Depend 2013;133(1):15-29. [PubMed]
  • Ray LA, Heydari A, Zorick T. Quetiapine for the treatment of alcoholism: scientific rationale and review of the literature. Drug Alcohol Rev 2010;29(5):568-75. [PubMed]

Evidence Summaries