[PLEASE NOTE: For the most complete & updated material on alcohol withdrawal, please see the Internet Book of Critical Care Chapter on this topic here]
Advantages of phenobarbital monotherapy
Neuroscience: Phenobarbital is theoretically superior to benzodiazepines
Clinical experience: Barbiturates are more powerful than benzodiazepines
Less delirium & paradoxical reactions?
Unlike benzodiazepines, phenobarbital doesn't cause paradoxical reactions (Ives 1991). This may reflect phenobarbital's more balanced inhibitory effect on the brain via two neurotransmitters, which protects against disinhibition.
Simplified pharmacology: Choose one GABAergic medication
|Relationship between cumulative phenobarbital dose and plasma phenobarbital concentration among patients treated for alcohol withdrawal (Tangmose 2010). We have added green lines indicating the plasma therapeutic range for phenobarbital (64-172 micromol/L = 15-40 ug/ml), an orange line indicating the level at which mild signs of toxicity are usually noted such as ataxia and nystagmus (225 micromol/L = 50 ug/ml), and a red line indicating the lowest level which has been associated with stupor or coma (>280 micromol/L = 65 ug/ml)(Lee 2013).|
Improved pharmacokinetics with intravenous phenobarbital?
Evidence regarding phenobarbital monotherapy
In Denmark barbital, a long-acting barbiturate, has been the drug of choice in the treatment of DT for many years. It was introduced in the beginning of this century (Moller 1909). In following discussions the importance of repeated, often large doses, (that is, 0.5-1 gram), in the initial stage of the disorder was stressed. The aim of the treatment was to sedate the patient to such a degree that he fell asleep and then slept for several hours. After this “critical sleep” the symptoms often disappeared completely. The treatment as outlined in the first reports was found so favorable that barbital has been preferred by Danish psychiatrists for several decades – Kramp 1978
Phenobarbital monotherapy: Nuts and bolts
- Although benzodiazepines are regarded as the mainstay of treatment for alcohol withdrawal, there has never been an adequately powered RCT comparing benzodiazepines vs. phenobarbital.
- Benzodiazepines occasionally fail to control alcohol withdrawal, and may promote agitated delirium. In contrast, phenobarbital is more effective and doesn't cause paradoxical agitation.
- Some countries have extensive experience treating alcohol withdrawal with phenobarbital monotherapy. Available evidence supports the safety and efficacy of this approach.
- Phenobarbital monotherapy consists of a gradual dose titration as shown below. Once a therapeutic phenobarbital level is reached, this will gradually auto-taper and provide ongoing protection from seizures or recurrent withdrawal.