What are the dangers of mixing illicit benzodiazepines (BZDs)?

Dangers of Mixing Illicit Benzodiazepines

Mixing illicit benzodiazepines creates a significant risk of respiratory depression, overdose, and death, particularly when combined with other central nervous system depressants such as opioids or alcohol. 1

Primary Dangers of Mixing Benzodiazepines

Respiratory Depression and Death

• When multiple benzodiazepines are used together, they have a synergistic effect on respiratory depression, which can lead to life-threatening respiratory arrest 1
• The risk of respiratory depression is dramatically increased when benzodiazepines are combined with other CNS depressants, with studies showing hypoxemia occurring in up to 92% of subjects and apnea in 50% of cases 2
• Benzodiazepines alone rarely cause fatal overdoses, but when combined with other substances, particularly opioids or alcohol, the risk of death increases 3-10 fold 1

Increased Risk of Overdose

• Illicit benzodiazepines often have unknown potency, purity, and may contain adulterants that increase overdose risk 1
• Combining different benzodiazepines with varying half-lives can lead to unpredictable cumulative effects and dangerous levels of sedation 3
• Overdose symptoms include confusion, dysarthria, lethargy, diminished reflexes, ataxia, hypotonia, and in severe cases, respiratory depression and coma 3

Dependence and Withdrawal

• Using multiple benzodiazepines increases the risk of developing physical dependence and addiction 3
• Abrupt discontinuation after regular use of multiple benzodiazepines can lead to severe withdrawal symptoms including 3:
  • Acute withdrawal: anxiety, blurred vision, headache, hypertension, insomnia, muscle pain, panic attacks, tremor
  • Severe withdrawal: catatonia, convulsions, delirium tremens, hallucinations, psychosis, seizures, and suicidality
  • Protracted withdrawal syndrome: symptoms lasting weeks to more than 12 months

Cognitive and Behavioral Impairment

• Combining benzodiazepines causes enhanced sedation and impaired coordination, significantly increasing the risk of accidents and injuries 1
• Disruptive sleep-related behaviors may occur, including sleepwalking, sleep-eating, sleep-driving, and sexual behavior during sleep 1
• Cognitive impairment is worsened with multiple benzodiazepines, affecting memory, attention, and decision-making 4

High-Risk Scenarios

Polysubstance Use

• The combination of multiple benzodiazepines with opioids is particularly dangerous, with the FDA issuing a black box warning about this combination 1, 3
• Alcohol use with multiple benzodiazepines dramatically increases the risk of respiratory depression and death 1, 5
• Even when benzodiazepines are the primary drugs of abuse, death is more often associated with polysubstance use 3

Vulnerable Populations

• Elderly individuals are at higher risk of adverse effects from multiple benzodiazepines due to slower metabolism and increased sensitivity 1, 2
• People with pre-existing respiratory conditions (COPD, sleep apnea) face heightened risks of respiratory failure 2
• Individuals with hepatic or renal impairment have reduced clearance of benzodiazepines, increasing toxicity risk 2

Emergency Management

Overdose Recognition and Response

• Signs of benzodiazepine overdose include severe drowsiness, confusion, slurred speech, poor coordination, diminished reflexes, respiratory depression, and unconsciousness 3
• Flumazenil is a specific benzodiazepine antagonist that can reverse sedative effects but should be used cautiously as it can precipitate seizures in dependent individuals 1, 3
• Flumazenil has no role in cardiac arrest related to benzodiazepine poisoning 1

Medical Intervention

• If combined opioid and benzodiazepine poisoning is suspected, naloxone should be administered first for respiratory depression 1
• Supportive care is the mainstay of treatment for benzodiazepine overdose, including airway management and intravenous fluids 3
• Contacting poison control (1-800-222-1222) is recommended for guidance on managing benzodiazepine overdoses 3

Harm Reduction Strategies

• Avoid mixing benzodiazepines with each other or with other CNS depressants 1
• If using benzodiazepines, start with the lowest possible dose and avoid increasing without medical supervision 3
• Never abruptly discontinue benzodiazepines after regular use; a gradual taper is necessary to prevent dangerous withdrawal symptoms 3
• Have naloxone available if there is any risk of opioid co-use 1