Background: Alcohol use disorder (AUD) and alcohol withdrawal syndrome (AWS) are common problems in hospitals. Benzodiazepines are considered the standard for treating and preventing AWS. Numerous review articles and guidelines have recommended that benzodiazepine dosing be based on objectively measured symptoms of withdrawal rather than a fixed dose regimen. The most commonly used scale for measuring withdrawal is the revised Clinical Institute of Withdrawal Assessment (CIWA). Nevertheless, some authors have questioned the superiority of symptom triggered therapy. It has also been reported that patients without AUD may be placed on symptom triggered protocols inappropriately and that symptom triggered protocols for inpatients were associated with increased mortality and length of stay at one hospital. Given this uncertainty, we undertook a systematic review of all randomized controlled trials (RCTs) comparing symptom triggered therapy to fixed dose schedules.

Methods: A systematic literature search was conducted for RCTs of patients with AWS that compared fixed dose schedules to symptom triggered therapy. Our search included MEDLINE, EMBASE and the Cochrane Registry. Symptom triggered therapy was defined as any regimen that used a standardized withdrawal scale to dose medication as needed without a standing order. Risk of bias was assessed using the Cochrane Collaboration’s bias assessment tool. Outcomes from included studies were pooled using a random-effects model. Heterogeneity was estimated using the I² statistic. The review protocol was registered in the Prospero database.

Results: 1666 studies were screened for inclusion. Six studies including 664 patients met inclusion criteria. There were no deaths and only two seizures, one of which occurred in symptom triggered therapy and one in fixed dose therapy. Three studies reported delirium, which occurred in 4 out of 164 patients randomized to symptom triggered therapy compared to 6 out of 164 randomized to fixed dose therapy (odds ratio, 0.64 [95% CI, 0.17-2.47]). Three studies reported total duration of therapy, which was 63.8 hours less in the symptom triggered group (95% CI, 41.7-85.9 hours; p<0.001). Six studies reported total benzodiazepine dosage, which was 16.6 mg less in the symptom triggered group (95% CI, 8.1-25.2 mg; p<0.001). Overall, risk of bias was low except for the outcomes of therapy duration and total benzodiazepine dose which were judged as high risk of bias.

Conclusions: There is no significant difference between symptom triggered therapy and fixed dose therapy in terms of mortality, seizure or delirium. Studies of symptom triggered therapy did report less total benzodiazepine dosage and shorter duration of detoxification, but these outcomes had high risk of bias.

IMAGE 1: Difference in Mean Total Benzodiazepine Dose (mg lorazepam): Symptom Triggered Therapy (STT) vs Fixed Dose Therapy (FDT)