How to manage benzodiazepine (benzos) prescriptions in a patient with a history of benzodiazepine overdose and potential substance abuse?

Managing Benzodiazepine Prescriptions After Overdose

Do not prescribe benzodiazepines to patients with a history of benzodiazepine overdose, particularly when substance use disorder or concurrent opioid use is present, as the risks of fatal respiratory depression and repeat overdose far outweigh any potential benefits. 1

Risk Assessment Framework

After a benzodiazepine overdose, immediately evaluate these critical risk factors before considering any future benzodiazepine prescribing:

• History of substance use disorder - This represents a near-absolute contraindication to benzodiazepine prescribing, as abuse and misuse commonly involve concomitant use of other medications, alcohol, and illicit substances, which is associated with increased frequency of serious adverse outcomes including death 1, 2

• Concurrent opioid use - Benzodiazepines combined with opioids cause a near quadrupling of overdose death risk compared to opioids alone, making co-prescription extremely dangerous 1

• Prior overdose history - Patients with previous overdose are at markedly increased risk for repeat overdose and should not receive benzodiazepines 1

• Benzodiazepine dependence - Physical dependence develops from continued therapy, and these patients face life-threatening withdrawal reactions if benzodiazepines are abruptly discontinued 2

The Default Position: Discontinuation

In most cases, benzodiazepines should be discontinued entirely after an overdose event. 1, 2

The appropriate approach depends on whether the patient was already taking benzodiazepines chronically:

For Patients NOT on Chronic Benzodiazepines

• Do not restart or initiate benzodiazepine therapy - The overdose demonstrates inability to safely use these medications 1, 2

• Provide alternative treatments for anxiety or insomnia (non-benzodiazepine options, cognitive behavioral therapy, SSRIs for anxiety disorders) 1

• Offer naloxone prescription given the high likelihood of polysubstance use involving opioids 1

For Patients on Chronic Benzodiazepines

• Initiate a gradual taper rather than abrupt discontinuation - Abrupt cessation can precipitate life-threatening withdrawal including seizures, delirium tremens, and death 1, 2

• Use a slow taper schedule: reduce the benzodiazepine dose by 25% every 2-4 weeks, or even slower (10% per month) for patients on long-term therapy 1

• Never abruptly discontinue benzodiazepines in dependent patients - This constitutes a medical emergency risk 2

• Monitor closely for withdrawal symptoms: anxiety, insomnia, tremor, seizures, hallucinations, and autonomic instability 2

When Benzodiazepines Might Be Continued (Rare Exceptions)

The only scenario where continuing benzodiazepines might be considered is in a patient with severe, treatment-refractory seizure disorder where benzodiazepines are medically necessary for seizure control. Even then:

• Implement maximum risk mitigation strategies 1

• Check prescription drug monitoring program (PDMP) data at every visit to identify concurrent controlled substances 1

• Prescribe naloxone given the overdose history 1

• Increase monitoring frequency substantially 1

• Involve addiction medicine specialists and psychiatry 1

• Use the lowest effective dose 1

• Avoid any concurrent opioid prescribing under all circumstances 1, 2

Critical Safety Measures

If benzodiazepines must be continued in exceptional circumstances:

• Review PDMP data before every prescription - This identifies dangerous combinations and doctor shopping behavior 1

• Prescribe naloxone - Overdose history is a Class A indication for naloxone co-prescription 1

• Avoid all concurrent CNS depressants - Never prescribe opioids, muscle relaxants, or hypnotics with benzodiazepines in this population 1

• Arrange addiction treatment referral - Patients with overdose history likely have substance use disorder requiring specialized treatment 1

• Do not abandon the patient - Discontinuing care based on overdose history can worsen outcomes and constitutes patient abandonment 1

Common Pitfalls to Avoid

• Never restart benzodiazepines "because the patient requests them" - Addiction involves strong drug-seeking behavior that should not guide prescribing 2

• Do not use flumazenil for chronic management - This benzodiazepine antagonist is only for acute overdose reversal and precipitates dangerous withdrawal in dependent patients 1, 3, 4

• Avoid the trap of "low-dose dependency" - Even therapeutic doses cause dependence in 30-45% of chronic users, and these patients will experience withdrawal 5

• Never combine benzodiazepines with opioids - This combination is explicitly warned against in FDA boxed warnings due to profound sedation, respiratory depression, coma, and death risk 2

Documentation Requirements

When making prescribing decisions after overdose:

• Document the overdose event, substances involved, and circumstances 1

• Record your risk-benefit analysis if continuing benzodiazepines 1

• Document PDMP review findings at each visit 1

• Note patient education about overdose risks and naloxone 1

• Document referrals to addiction treatment services 1