(073) Clinical course and recommendations for the management of benzodiazepine withdrawal delirium: a systematic review of case reports

Abstract: Background

Benzodiazepines are widely prescribed medications (Olfson 2015), and withdrawal can cause a variety of symptoms including tremors, anxiety, delirium, and seizures. The literature surrounding GABAergic withdrawal delirium (WD) has focused more prominently on alcohol WD rather than benzodiazepine WD despite the fact that both are commonly encountered on consultation-liaison services. We present a systematic review of benzodiazepine-WD case reports with the goal to consolidate the literature on its common presentation and recommendations for treatment.

Methods

We conducted a literature search of English articles in major databases (MEDLINE, Embase, PsycInfo, Scopus, and Web of Science) published between 1946 and 11/18/2021. Case reports and series were included. Search terms included “benzodiazepine,” all types of benzodiazepines, “withdrawal,” and “delirium.” We excluded studies describing patients with alcohol and zolpidem withdrawal delirium.

Results

A total of 1752 articles were screened, and 13 studies were included. Eighteen cases of benzodiazepine WD were reported. All patients were treated with benzodiazepines for greater than six weeks prior to the onset of WD. The most commonly reported triggering event was accidentally missing medications after being admitted for surgery. On average, delirium developed within one week after benzodiazepine discontinuation and lasted for up to several weeks. Benzodiazepine reinitiation was the treatment of choice for all cases with some using antipsychotics for additional management. Standardized delirium scales were not used in any of the cases.

Discussion

There is a lack of research on benzodiazepine WD compared to uncomplicated benzodiazepine withdrawal. Risk factors for benzodiazepine withdrawal include high dose, long-term use, and short half-life benzodiazepines; however, it is unclear if these risk factors always correlate to risk of WD.

Though benzodiazepine reinitiation is the standard of care for uncomplicated withdrawal, these strategies may not be adequate in WD considering the complex underlying pathophysiology of WD. In cases of severely agitated WD, collateral strategies, such as those used for the management of delirium tremens (Schuckit 2014), deserve further investigation. Lastly, considering that the most common cause of WD in our review was iatrogenic (e.g. failure to continue outpatient regimens), routine use of Prescription Drug Monitoring Programs could greatly benefit as preventative measures.

Conclusion

Benzodiazepine withdrawal can manifest as delirium with various psychopathology. Prompt reinitiation of a benzodiazepine remains the mainstay of treatment, and clinicians should be cautious when abruptly discontinuing benzodiazepines regardless of clinical settings to minimize the risk of WD. Future study of large populations is needed to best quantify risk profiles of benzodiazepine WD and to clarify if there is a need for differential management from alcohol WD.

References

Olfson M, King M, Schoenbaum M. Benzodiazepine use in the United States. JAMA Psychiatry. 2015 Feb;72(2):136-42.

Schuckit MA. Recognition and management of withdrawal delirium (delirium tremens). N Engl J Med. 2014;371(22):2109-2113.