Benzodiazepines in Epilepsy: A US Perspective on Clinical Use, Pharmacology, Abuse Methods, and Public Health Considerations

Benzodiazepines (BZDs) are indicated for a range of therapeutic conditions and can improve patient outcomes when used appropriately. The role of BZDs in epilepsy management is essential in that they have long been first-line agents for acute seizure cessation, most notably including status epilepticus, with each BZD offering a unique pharmacokinetic profile. BZDs are commonly used to treat seizures because of their rapid onset, pronounced safety and tolerability profiles, and versatility of dosage forms and available routes of administration. Despite their clinical utility in a variety of therapeutic areas for a wide range of conditions, the potential for BZD misuse and abuse remains a topic of public health concern. Particularly in combination with other central nervous system depressants (e.g., opioids, gabapentin, and alcohol), misuse and abuse of BZDs are linked to serious and potentially fatal complications. As such, the US Food and Drug Administration has issued a boxed warning regarding concurrent use of BZDs and opioids, emphasizing the dangers of co-prescribing. Policies and prescribing safeguards are implemented to regulate and promote safe use of BZDs; however, such measures may unintentionally worsen patient care by limiting access for individuals that benefit from therapy for seizure control. The objective of this paper is to identify a practical balance between ensuring access to these essential medications for those who experience clinical benefit while also supporting safe prescribing of BZDs to minimize misuse and abuse. Findings from the present review support continued research, drug utilization policies, and patient education. Benzodiazepines come in many formulations with different properties and routes of administration. When taken as directed, different benzodiazepines are clinically important for many medical conditions. These drugs have well-known safety profiles, and some are effective for quickly treating seizures. However, intentional or accidental use that is too often or at higher doses is a form of misuse. In contrast, abuse is when the medication is taken on purpose for something it was not prescribed to treat. This article reviews the important role of benzodiazepines in epilepsy management and clarifies the risks of misuse and abuse. Notably, most hospitalizations for overdose involve abuse of other drugs at the same time. Long-term use of benzodiazepines, especially at high doses, may lead to misuse and abuse. People with another health condition, such as long-term pain or psychiatric disorders, may be at higher risk for abuse, particularly if they are using additional medications. Also, opioids and alcohol depress the nervous system and should not be combined with benzodiazepines. However, limiting use of these drugs may harm patients needing seizure control. Prescribers should be aware of these risks and work with patients to provide effective treatment while limiting the risk of misuse and abuse. Graphical abstract available for this article.