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Understanding Benzodiazepines and Their Role in Substance Use Disorders

Understanding Benzodiazepines and Their Role in Substance Use Disorders

Diagnostic flow diagram: co-occurring substance use and psychiatric disordersFIGURE. Diagnostic flow diagram: co-occurring substance use and psychi...
The use of benzodiazepines in patients with substance use disordersTABLE 1. The use of benzodiazepines in patients with substance use dis...
Tips for benzodiazepine prescribing: interpersonal dimensionTABLE 2. Tips for benzodiazepine prescribing: interpersonal dimension

For the past 30 years, there have been widely discrepant views on the use of benzodiazepines that range from complete avoidance to use as moderate- to high-dose maintenance therapy for certain anxiety disorders. In the early 21st century, high-potency benzodiazepines were suggested as the preferred agents for treating anxiety and panic disorders because of their rapid onset of action and the fact that older low-potency benzodiazepines were considered ineffective for panic disorder. The adverse effects due to tolerance (rebound anxiety) and dependence were discussed as well as the direct effects on memory, and treatment guidelines for anxiety disorders recommended shorter periods of use.

Benzodiazepines are no longer regarded as first-line treatment. The evolution of thought on the addictive potential of benzodiazepines ranges from low abuse potential to observations that benzodiazepines are frequently used in combination with drugs of abuse and are commonly seen in polydrug overdose scenarios.

Benzodiazepines are Schedule IV compounds, which means that as a group they have a low potential for abuse. Despite that assessment, alprazolam is the third most commonly diverted drug.


Data on the extent of use of benzodiazepines are available from the National Survey on Drug Use and Health (NSDUH) from the Substance Abuse and Mental Health Services Administration (SAMHSA).1 The most recent data from 2015 break out benzodiazepine preparations from other compounds: 29.7 million people (11.2% of the population) used benzodiazepine tranquilizers. Of that group, 17.6 million (6.6% of the population) used alprazolam-containing products.

Survey estimates of the use and misuse of benzodiazepines do not give any measure of morbidity or mortality. However, a 6-year review of medication-related incidents in England and Wales indicates that benzodiazepines ranked sixth after opioids, antibiotics, warfarin, heparin, and insulin for severe harm or death.2 Between 2010 and 2014, 2 of the top 10 drugs implicated in overdoses were diazepam and alprazolam.3 In the deaths involving these medications, 95% included the use of concomitant drugs. Moreover, 30% of fatal opioid overdoses in the US involve benzodiazepines.4

Clinical guidelines

Guidelines on benzodiazepine use have evolved over the years. Janicak and colleagues5 provide an algorithmic summary for anxiety disorders based on severity and chronicity. For the treatment of anxiety disorders, they reserve the use of benzodiazepines for inadequate response to behavior therapy, SSRIs plus behavior therapy, or TCAs and behavior therapy. At that point the initial recommendation is alprazolam/clonazepam. If initial treatment is at the severe level, they recommend alprazolam plus a TCA or an SSRI for the first month; if that is insufficient, “indefinite” alprazolam. There are additional therapies with or without benzodiazepines if that level of treatment is inadequate.

In the second edition of Principles and Practice of Psychopharmacology, Janicak and colleagues add clonazepam to the algorithm as another option for refractory anxiety. In subsequent editions, other antidepressants (venlafaxine, TCAs), alprazolam XR, SSRIs and SNRIs, and anticonvulsants (valproate, gabapentin) are all factored in at decision points. The basic position on benzodiazepines has been unaltered—limited use for the first month until the SSRI starts to work is preferred unless there is insufficient response, and in that case benzodiazepines are added at the level of various therapies as maintenance treatment for insufficient response.


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