What are the contraindications for prescribing benzodiazepines (BZDs) to patients, particularly those with a history of substance abuse, severe respiratory depression, sleep apnea, hepatic impairment, dementia, psychosis, anxiety disorders, or myasthenia gravis, and in geriatric individuals?

Benzodiazepines Contraindications

Benzodiazepines are absolutely contraindicated in patients with myasthenia gravis, severe respiratory insufficiency, severe hepatic insufficiency, sleep apnea syndrome, and acute narrow-angle glaucoma, according to FDA labeling. 1

Absolute Contraindications

The following conditions represent absolute contraindications where benzodiazepines must not be prescribed:

• Myasthenia gravis - benzodiazepines can exacerbate muscle weakness 1
• Severe respiratory insufficiency - risk of life-threatening respiratory depression 1
• Severe hepatic insufficiency - impaired drug clearance leads to accumulation and toxicity 1
• Sleep apnea syndrome - benzodiazepines worsen respiratory depression during sleep 1
• Acute narrow-angle glaucoma - benzodiazepines are contraindicated, though may be used in open-angle glaucoma with appropriate therapy 1
• Known hypersensitivity to benzodiazepines 1
• Pediatric patients under 6 months of age - insufficient clinical experience 1

Relative Contraindications and High-Risk Situations

Substance Use Disorders

The traditional position that benzodiazepines are absolutely contraindicated in patients with substance abuse history lacks strong empirical justification, but extreme caution is warranted. 1, 2

• Benzodiazepines should be used with extreme caution in patients with a history of alcohol or drug abuse 1
• Patients with substance use disorders who receive prescribed benzodiazepines have a 15% risk of developing benzodiazepine abuse compared to 6% in those not prescribed benzodiazepines 3
• Most benzodiazepine abusers concurrently abuse other substances; benzodiazepines are typically a secondary drug of abuse 2, 4
• Avoid benzodiazepines in patients with dependent personality types or active polysubstance abuse 5
• Co-occurring alcohol or benzodiazepine abuse is an indication for specialist referral 6

Respiratory Conditions

• Chronic respiratory insufficiency requires lower doses due to risk of respiratory depression 1
• Central sleep apnea is a risk factor for opioid overdose when benzodiazepines are combined with opioids 6

Hepatic Impairment

• Benzodiazepine clearance is reduced in hepatic dysfunction, requiring dose reduction 6
• Lorazepam, oxazepam, and temazepam are preferred in liver disease due to direct glucuronidation metabolism 7

Neuropsychiatric Conditions

• Avoid in uremic encephalopathy or delirium - benzodiazepines worsen the underlying condition and prevent accurate clinical assessment 8
• Patients with dementia experience greater risks of sedation, falls, cognitive impairment, and prolonged drug effects 8
• Psychiatric and paradoxical reactions (agitation, aggression) occur more commonly in children and elderly patients 1, 7

Geriatric Population

Elderly patients represent a high-risk population requiring special precautions, not absolute contraindication:

• Greater risks of sedation, falls, cognitive impairment, and prolonged drug effects 8
• Start with lowest effective doses (e.g., 2 mg diazepam once or twice daily initially) 1
• Benzodiazepines cause cognitive impairment, reduced mobility, unsafe driving skills, and decline in functional independence 8

Critical Drug Interactions (Relative Contraindications)

Opioid Co-Administration

Concomitant use of benzodiazepines with opioids can result in profound sedation, respiratory depression, coma, and death through cumulative and synergistic effects. 8

• The combination increases overdose risk dramatically 6
• If co-prescription is unavoidable, use lowest effective doses of both agents and monitor closely 6
• Patients should not drive or operate machinery until effects are determined 1

Other CNS Depressants

• Avoid combining with alcohol - additive psychomotor impairment and respiratory depression 7, 1
• Phenothiazines, narcotics, barbiturates, MAO inhibitors potentiate benzodiazepine effects 1
• Fatalities reported with concurrent use of benzodiazepines and high-dose olanzapine due to oversedation and respiratory depression 9, 7, 8

Duration-Related Contraindications

Long-term benzodiazepine use (>2-4 weeks) should be considered a relative contraindication in most patients:

• Prescriptions should ideally be limited to a few days, occasional/intermittent use, or courses not exceeding 2-4 weeks 8, 10
• Approximately 50% of patients prescribed benzodiazepines continue use for at least 12 months despite guidelines recommending short-term use only 8
• Regular use leads to tolerance, addiction, depression, and cognitive impairment 7
• Withdrawal reactions can be life-threatening, including seizures 1

Common Pitfalls to Avoid

• Do not assume short-acting benzodiazepines are safer - active metabolites still accumulate, especially in renal failure 8
• Never abruptly discontinue after prolonged use - use gradual taper over months to prevent withdrawal seizures 6, 1
• Do not use to manage delirium or encephalopathy itself - worsens the condition 8
• Avoid in patients requiring opioids for pain control unless absolutely necessary with enhanced monitoring 6
• Do not prescribe without considering psychiatric comorbidities - depression with suicidal tendencies requires protective measures 1