What causes 'blacking out' episodes in patients taking drugs, such as benzodiazepines (e.g. alprazolam) or opioids?

From the Guidelines

Blackout episodes in patients taking benzodiazepines like alprazolam or opioids are primarily caused by these drugs' effects on memory formation and consciousness, leading to anterograde amnesia. These medications interfere with the brain's ability to form new memories while still allowing the person to function. Benzodiazepines specifically enhance the effects of GABA, an inhibitory neurotransmitter, which suppresses activity in brain regions responsible for memory consolidation, particularly the hippocampus 1. Opioids cause blackouts through their sedative properties and by depressing central nervous system function. These effects are dose-dependent and significantly worse when combined with alcohol or other central nervous system depressants. Factors that increase blackout risk include:

• Taking higher doses than prescribed
• Combining substances
• Having liver impairment that slows drug metabolism
• Being elderly
• Having low body weight Patients should be advised to take these medications exactly as prescribed, never combine them with alcohol, and immediately report any memory lapses to their healthcare provider, as blackouts can lead to dangerous situations where patients engage in activities they cannot later recall 1. It is also important to note that sudden cessation of these medicines can lead to physical and psychological withdrawal symptoms, and if there is a decision to stop, patients treated long-term with any of these medicine classes studied should be offered careful tapering and support 1. A commonly used tapering schedule that has been used safely and with moderate success is a reduction of the benzodiazepine dose by 25% every 1–2 weeks 1. Clinicians should communicate with mental health professionals managing the patient to discuss the patient’s needs, prioritize patient goals, weigh risks of concurrent benzodiazepine and opioid exposure, and coordinate care 1.

From the FDA Drug Label

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. The use of benzodiazepines, including lorazepam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Taking benzodiazepines with opioid medicines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, breathing problems (respiratory depression), coma and death

The causes of "blacking out" episodes in patients taking drugs, such as benzodiazepines (e.g. alprazolam) or opioids, include:

• Concomitant use of benzodiazepines and opioids, which may result in profound sedation, respiratory depression, coma, and death 2
• Abuse, misuse, and addiction to benzodiazepines, which can lead to overdose or death 2
• Concomitant use of other medications, alcohol, and/or illicit substances with benzodiazepines, which is associated with an increased frequency of serious adverse outcomes 2
• Severe drowsiness, breathing problems (respiratory depression), coma and death caused by taking benzodiazepines with opioid medicines, alcohol, or other central nervous system depressants (including street drugs) 2

From the Research

Causes of "Blacking Out" Episodes

The causes of "blacking out" episodes in patients taking drugs, such as benzodiazepines or opioids, can be complex and multifaceted. Some possible factors include:

• Benzodiazepine withdrawal: Withdrawal from benzodiazepines can cause seizures, which may lead to "blacking out" episodes 3, 4.
• Overdose: Concurrent use of benzodiazepines and opioids can increase the risk of overdose, which may result in "blacking out" episodes 5.
• Substance use disorders: Patients with substance use disorders may be more likely to experience "blacking out" episodes due to the interactions between different substances 6, 7.
• Polydrug abuse: The use of multiple substances, including benzodiazepines and opioids, can increase the risk of "blacking out" episodes 7.
• High-dose or long-term use: High-dose or long-term use of benzodiazepines or opioids can increase the risk of "blacking out" episodes 3, 4.

Risk Factors

Several risk factors can increase the likelihood of "blacking out" episodes in patients taking benzodiazepines or opioids, including:

• Concurrent use of multiple substances: The use of multiple substances, including benzodiazepines, opioids, and non-benzodiazepine sedative-hypnotics, can increase the risk of "blacking out" episodes 5.
• Higher opioid dosage strengths: Higher opioid dosage strengths can increase the risk of "blacking out" episodes 5.
• Elderly age: Elderly patients (age ≥ 65 years) may be more likely to experience "blacking out" episodes due to the interactions between benzodiazepines and opioids 5.
• History of previous overdose: Patients with a history of previous overdose may be more likely to experience "blacking out" episodes 5.
• Substance use disorder: Patients with substance use disorders may be more likely to experience "blacking out" episodes due to the interactions between different substances 6, 7.