Skip to content

Benzodiazepine Injury Syndrome and Recovery

Unlike most other medications, for benzodiazepines there is often a significant period of time after withdrawal is complete where patients still experience a variety of the same symptoms they had while tapering.  This can extend well beyond the time where there is any active benzodiazepine or metabolite present, sometimes for years after the completion of withdrawal.  Post-withdrawal patients also often report new symptoms, or (less frequently) symptoms that have increased beyond the levels experienced during use or while tapering. Thus, there is evidence of a potentially long-lasting Benzodiazepine Injury Syndrome (BZIS) in up to 40% of long-term BZ users[1].  Some have suggested calling this phenomena “Benzodiazepine Induced Brain Injury”, but since BZs bind to neural and non-neural tissue throughout the body, there is no evidence that the physiological alterations made by benzodiazepines are restricted to the brain.  However, there is the possibility of symptoms increasing in reaction to increases in Net Neural Load.  This is similar to Central Sensitization, but virtually all stimuli – whether pleasurable or not – can add together to increase the number and severity of BZIS symptoms presented[2].

Thus, the clinician’s job is not necessarily done once withdrawal is complete.  Affected patients need the clinician to assist and guide them through this confusing critical recovery period.

While the symptoms associated with BZIS can usually be found on the list of overall benzodiazepine withdrawal symptoms, the existence of BZIS still presents a dilemma to the clinician.  Given the wide variety of withdrawal symptoms and possibly protracted timeframe, other diagnoses may be indicated for the current complaints.  When do you attribute the symptoms to withdrawal or recovery, and when do you pursue another possible diagnosis?  Unfortunately, there is no guideline for this process.  This determination is usually made based on the experience level of the clinician in the area of benzodiazepine withdrawal and recovery.  For those with minimal experience with BZWS and BZIS, we would like to suggest a simple heuristic:

Complaints that follow the increase-decrease pattern of waves and windows are more likely to be associated with Benzodiazepine Injury Syndrome.

Thus, when the symptoms are not emergent, “reassure, wait and see”.

Note that, unlike most addiction-prone drugs, there is little evidence of post-withdrawal patients craving benzodiazepines.  Most are seeking relief from the ongoing symptoms of physiologic dependence.

References
[1] Tyrer P et al. Gradual withdrawal of diazepam after long-term therapy. Lancet. 1983;1(8339):1402-1406 Abstract
[2] John F. Peppin, Joseph V. Pergolizzi (Jr.), Robert B. Raffa, Steven L. Wright et al. The Benzodiazepine Crisis: An Overview of the Down-Side of an Overused Drug Class. Oxford University Press, 2020.