Barbiturate withdrawal has become a less common problem recently with the widespread use of the oral phenobarbitone loading regime and the decreased use of barbiturates for both sedation and epilepsy with a consequent decrease in barbiturate abuse.
Significant withdrawal is expected in patients using > 500 mg amylobarbitone equivalent for > 5 months. Admit all patients showing early signs of withdrawal such as hyperactivity, anxiety or hyperreflexia - do not attempt to manage barbiturate withdrawal as an outpatient or in a nonmedical setting.
However, problems can still occur with the unsuspected use of short acting barbiturates and when the half life of phenobarbitone is shortened by techniques such as urine alkalinisation or because of hepatic enzyme induction.
Barbiturate withdrawal may be associated with significant morbidity and even mortality. The major complications are seizures and delirium and the frequency with which these occur is closely related to the elimination half-life.p
The current treatment is to load patients withdrawing from short acting barbiturates with phenobarbitone. The long half life of phenobarbitone means that for most patients the withdrawal is uneventful. However there are patients in whom for various reasons phenobarbitone has a relatively short half life and therefore they have an increased risk of complications. Supplementary doses are often recommended in this situation and have the effect of prolonging the “apparent” half life.
However, excessive supplementation has the disadvantages of prolonging the withdrawal and encouraging drug seeking behaviour in the patient. Therefore minimum supplementation is desirable. We supplement patients with a phenobarbitone half life of less than 50 hours on the basis that there are no reports of complications occurring in patients with elimination half lives > 50 hours.
We have developed a nomogram to aid in the calculation of the supplementary doses. However the vast majority of patients will not require supplementation.
It is safe to wait for concentrations as the major complications of barbiturate withdrawal occur after 48-72 hours.
Patients are given phenobarbitone 120 mg/h until they develop moderate toxicity.
We recommend the use of a nomogram to calculate whether supplementation is needed. This method is suitable for any patients undergoing barbiturate detoxification but is particularly useful if they have a history of seizures, multiple drug detoxification or are in the post-overdose setting.
Patients have phenobarbitone concentrations taken at least 2 hours after loading (peak concentration) and then 12-24 hours later (whenever most convenient). From the peak concentration a line is drawn parallel to the dark diagonal lines (representing a half life of 50 hours). If the second concentration falls above this line no supplementary doses are required and no further concentrations unless the patient becomes symptomatic. If the second concentration is below this line, a line should be drawn between the two concentrations and extended to the 24 hour mark. There the difference between the ideal (t1/2=50 h) and the real concentration at 24 hours will be shown. Supplementary doses can be calculated simply by measuring the number of spaces between these two points with each space representing 5% of the loading dose to be required per 24 hours. The following day concentrations can again be measured (with a line drawn from the “ideal” concentration at 24 hours to the new concentration). The difference can again be measured, this time at the 48 hour mark and supplementation given again. The process is repeated every 24 hours until concentrations are less than 30 micromol/L (7 mg/L). If at any time the concentration is above the original (t1/2=50 h) line no supplementary doses are required. Note that if phenobarbitone supplements are required at 24 hours and NOT given the subsequent calculation of supplementation will not work (it will still indicate whether supplementation is necessary). This method has the advantage of being simple and allowing for variations in the half life. A worked example is here.
If the half life remains constant, supplementation will reduce by roughly 30% each day. If for some reason concentrations are unavailable on any day after the initial calculation of half life then this will give an approximation of the supplementary dose required.
Boisse NR, Okamoto M. Physical dependence to barbital compared to pentobarbital. IV. Influence of elimination kinetics. J Pharmacol Exp Ther. 1978;204:526-540.
Buckley NA, Foy A. Barbiturate withdrawal - case report and nomogram. Drug and Alcohol Review 1995;14(4):385-388.
Fraser HF, Shaver MR, Maxwell ES & Isbell H. Death due to withdrawal of barbiturates: Report of a case. Ann Intern Med 1953;38:1319-1325.
Janacek E, Kapur BM, Devenyi P. Oral phenobarbital loading: a safe method of barbiturate and non-barbiturate hypnosedative withdrawal. CMAJ 1987;137:410-412.
Martin PR, Kapur BM, Whiteside EA & Sellers EM. Intravenous phenobarbital therapy in barbiturate and other hypnosedative withdrawal reactions: a kinetic approach. Clin Pharmacol Ther 1979;26:256-264.
Robinson GM & Sellers EM. Diazepam withdrawal seizures. Can Med Assoc J 1982;126:944-945.
Robinson GM, Sellers EM, Janacek E. Treatment of barbiturate and hypnosedative withdrawal by a multiple oral phenobarbital loading dose technique. Clin Pharmacol Ther 1981;30:71-76.
Waddell WJ & Butler TC. The distribution and excretion of phenobarbital. J Clin Invest 1957;36:1217-1226.
Wikler A. Diagnosis and treatment of drug dependence of the barbiturate type. Am J Psychiatry 1968;125:758-765.
Wulff MH. The barbiturate withdrawal syndrome. A clinical and electroencephalographic study. Electoencephalogr Clin Neurophysiol 1959; Suppl 14:1-173.