Acamprosate modulates NMDA receptor transmission and GABA-A transmission and helps decrease the highly glutamatergic states associated with alcohol withdrawal. It isabsorbed from the gastrointestinal tract over four hours and has peak concentration 5-7 hours post ingestion and achieves a steady state after 7 days of usage.
Common side effects include diarrhoea, nausea, vomiting, skin rash and reduced libido. It is contraindicated in renal failure and Child Pugh C liver cirrhosis.
The common dose is 2 tablets tds if over 60kg or 2 tablets mane, 1 midi and 1 nocte if less than 60kg.
Disulfiram
Disulfiram irreversibly inhibits aldehydye dehydrogenase which is the enzyme that converts acetaldehyde to acetate and leads to an accumulation of acetaldehyde after drinking alcohol. Acetaldeyde causes an unpleasant reaction and acts as a psychological deterrent to drinking as an 'aversive therapy'. The inhibition of enzyme activity occurs in 12 hours and lasts more than 5 days.
The symptoms that it invokes includes flushing, headache, palpitations, dyspnoea, hypotension, prostration and ECG changes. Symptom onset can start within 10 minutes, peaks at 20-30 minutes and lasts for 1-2 hours. Patients need to abstain from alcohol one days before taking medication and for one week after cessation of treatment.
Common side effects include drowsiness, tiredness, confusion, headache, neuropathies, gastric upset, garlic taste and optic neuritis. Disulfiram is contraindicated in psychosis, IHD, severe renal or hepatic disease, pregnancy, allergies to compounds in medication and cognitive issues.
Disulfiram also interacts with a lot of medications including metronidazole, isoniazid, phenytoin, benzodiazepines and anticoagulants.
The dose is 100mg daily for 1-2 weeks then 200mg daily for 6 weeks to 6 months though duration of treatment is variable and maximum dosage can be 300mg daily.
Baclofen
Baclofen is a GABA-B receptor antagonist that suppresses alcohol mediated dopamine release. It has limited hepatic metabolism and well tolerated in those with chronic liver disease. It can cause sedation, drowsiness, headache, rash and urinary difficulties. Baclofen needs to be weaned gradually to avoid withdrawal syndrome such as confusion, anxiety, seizures, delusions, hallucinations and delirium.
The dose of baclofen for alcohol use disorder is given three times per day initially at 15-30mg daily (5-10mg tds) and increased to a maximum daily dose of 150mg if required.
Topiramate
Topiramate reduces glutamatergic function and enhance GABA-A receptor activity or modulate impulsivity. Common side effects include sedation, unsteadiness, paraesthesia, headache, dizziness, depression, anxiety, cognitive impairment and glaucoma. It is contraindicated in pregnancy.
The dose starts at 25mg bd and can be up to 150mg bd.