Benzodiazepine loading versus symptom-triggered treatment of alcohol withdrawal: a prospective, randomized clinical trial

Gen Hosp Psychiatry. 2012 Aug 13
Benzodiazepine loading versus symptom-triggered treatment of alcohol withdrawal: a prospective, randomized clinical trial.
Maldonado JR, Nguyen LH, Schader EM, Brooks JO 3rd
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine
PMID: 22898443

This was a randomized but open label trial comparing loading with long acting benzo (diazepam) to symptom triggered short acting benzo (lorazepam).


Over 12 months, 47 patients were randomized mostly at the Palo Alto VA but some at Stanford. 


Loading protocol (LP)

On day 1: Load with diazepam 20 mg by mouth every 2 h × 3 doses. (or diazepam 10 mg IV every 1 h × 6 doses). Hold for excessive sedation or RR<10.Additional diazepam 10 mg by mouth or intravenously may be administered every 2 h as needed for residual withdrawal symptoms (e.g., CIWA-Ar>8 or vital signs alteration suggestive of a hyperadrenergic state, such as SBP>140, DBP>90, HR>100). Hold for excessive sedation or RR<10.

Symptom-triggered protocol (STP)

Lorazepam 1 to 2 mg, by mouth or intravenously, may be administered every 2 h as needed for active withdrawal symptoms (e.g., CIWA-Ar>8 or vital signs alteration suggestive of a hyperadrenergic state, such as SBP>140, DBP>90, HR>100). Hold for excessive sedation or RR<10.RR=respiratory rate; SBP=systolic blood pressure; DBP=diastolic blood pressure; HR=heart rate.

There were no statistically significant differences although the diazepam loading protocol was marginally better with  69.6% symptom free at 72 hours vs 41.7% for the lorazepam symptom triggered protocol.  The average rate of CIWA improvment per day was -2.3 for the loading dose vs  -1.5 for the symptoms triggered.  Total diazepam 103 mg for the loading protocol and 92.4 mg diazepam equivalents (assuming 1 mg of lorazepam to 5 mg of diazepam) for the symptom triggered pts. 

Two patients, one in each group with DTs severe enough to require transfer to ICU.

This study conflates two questions, short vs long acting benzo and loading vs symptom triggered dosing.  The short answer is that it doesn't make much difference, or at least no statistically different difference. The slight edge to the loading protocol could be attributed to either the early dosing or the potential advantages of long acting benzo.