Content area
Full Text
Background
The development of alcohol dependence appears to involve changes in brain neurotransmission. In animals, acute administration of alcohol blocks brain N-methyl-D-aspartate (NMDA) receptors, which are normally stimulated by glutamate, the main excitatory neurotransmitter in the central nervous system. With chronic administration, the number of NMDA receptors in the brain increases, as does the number of 'L type' calcium channels, while the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is reduced. 1 , 2 Assuming similar changes were to occur in a person with alcohol dependence, their excitatory effects could cause symptoms of alcohol withdrawal (e.g. anxiety, insomnia, craving) if the individual suddenly stopped drinking (so removing alcohol's inhibitory effects). Such symptoms may help to perpetuate dependence.
There are few drug treatments that reliably maintain abstinence in patients with alcohol dependence. Disulfiram can help to reduce a patient's drinking but, in general, its use needs to be supervised (e.g. by the patient's partner) to help ensure adherence to therapy. 3 Evidence suggests that naltrexone , an opioid antagonist, used with psychosocial therapy (e.g. supportive counselling, psychotherapy to foster development of coping skills, group therapy), can help dependent patients to abstain from alcohol. 4 - 6 In the UK, naltrexone is neither licensed nor widely used for this indication.
Pharmacology
Acamprosate is derived from taurine, an amino acid. Its structure resembles those of GABA and glutamate. In animals, acamprosate crosses the blood-brain barrier and, in the brain, reduces the effects of excitatory amino acids (e.g. glutamate) and modifies GABA neurotransmission. 7 In animals, acamprosate reduces alcohol consumption, particularly in those previously made alcohol dependent. 7
In humans, usually less than 10% of an oral dose of acamprosate is absorbed through the gastrointestinal tract into the circulation in the first 24 hours. The drug does not bind to plasma proteins and is not significantly metabolised. Excretion occurs via the urine and is slowed if renal function is impaired.
Clinical studies
Acamprosate has been evaluated in several double-blind, placebo-controlled trials involving patients who had previously undergone alcohol detoxification. 8 - 14 Many participants (18-80% of all those randomised) did not complete these trials - a standard feature of studies involving patients with alcohol dependence. Typical reasons for failing to complete a study included loss to follow-up,...