What are the effects of Benzodiazepine (BZD) agonists?

From the Guidelines

Benzodiazepine agonists should be avoided due to their widely known harms and adverse effects, including risk for dependency, falls, and cognitive impairment, which substantially outweigh their benefits in treating chronic insomnia disorder. The effects of Benzodiazepine (BZD) agonists are sedative, hypnotic, anxiolytic, anticonvulsant, and muscle relaxant, resulting from their enhancement of the neurotransmitter gamma-aminobutylic acid (GABA) at the GABA-A receptor 1. Common benzodiazepines include diazepam (Valium), alprazolam (Xanax), lorazepam (Ativan), and clonazepam (Klonopin), which are primarily used to treat anxiety disorders, insomnia, seizures, alcohol withdrawal, and as pre-anesthetic medications.

Key points to consider when evaluating the effects of BZD agonists include:

• Their potential to improve sleep efficiency, sleep onset latency, sleep quality, total sleep time, and wake after sleep onset compared with placebo 1
• The risks associated with their use, such as dependency, diversion, falls, and cognitive impairment in older patients, hypoventilation in patients with respiratory conditions, and neuromuscular diseases 1
• The recommendation against their use for treatment of chronic insomnia disorder due to the substantial outweighing of benefits by harms 1
• The importance of administering nonbenzodiazepine BZRAs at the lowest effective dose and for the shortest possible duration, with counseling on potential risks, if prescribed as an alternative 1

In clinical practice, it is crucial to weigh the potential benefits of BZD agonists against their well-documented risks and to consider alternative treatments that may offer a more favorable risk-benefit profile, especially for chronic conditions like insomnia. The most recent and highest quality evidence supports a cautious approach to the use of BZD agonists, emphasizing the need for careful patient selection, dosing, and monitoring to mitigate adverse effects 1.

From the FDA Drug Label

Abuse and misuse of benzodiazepines may lead to addiction Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death The following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo The following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death

The effects of Benzodiazepine (BZD) agonists include:

• Addiction: Abuse and misuse of benzodiazepines may lead to addiction
• Adverse reactions: Such as abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo
• Severe adverse reactions: Including delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death
• Respiratory depression: Associated with an increased frequency of serious adverse outcomes, including overdose, or death, especially when used with other CNS depressants such as opioids and alcohol 2, 3
• Physical dependence: Benzodiazepines may produce physical dependence from continued therapy, and abrupt discontinuation or rapid dosage reduction may precipitate acute withdrawal reactions, including seizures 2, 3
• Tolerance: Tolerance to benzodiazepines may develop from continued therapy 2, 3, 4

From the Research

Effects of Benzodiazepine (BZD) Agonists

• Benzodiazepines have been found to be effective in the short-term management of panic disorder, with studies showing that alprazolam, clonazepam, diazepam, and lorazepam can have positive effects on anxiety and panic attacks 5.
• However, the use of benzodiazepines is also associated with a variety of adverse effects, including intoxication, dependence, rebound, withdrawal, hostility, and affective disturbances 5, 6.
• Long-term use of benzodiazepines can lead to protracted and severe symptoms, even years after discontinuation, including anxiety, insomnia, nervousness, digestive problems, and uncontrollable anger 7.
• The benefits of benzodiazepine treatment may outweigh the risks for patients with panic disorder, but the risks and benefits of treatment should be carefully considered and patients should be informed about the potential for difficult withdrawal 5, 8.

Adverse Effects and Risks

• Benzodiazepines can cause a range of adverse effects, including sedation, cognitive impairment, and increased risk of falls and fractures 6, 8.
• The use of benzodiazepines can also lead to dependence and addiction, particularly with long-term use 6, 7.
• As-needed use of benzodiazepines may be associated with increased patient preference for benzodiazepines over placebo, continued use, and greater impairment on cognitive factors associated with positive long-term anxiety management 9.

Alternatives and Discontinuation

• Alternatives to benzodiazepines, such as psychotherapy, relaxation techniques, and serotonergic agents, may be effective for managing anxiety and insomnia 6, 8.
• Deprescribing benzodiazepines, or tapering slowly, can be an effective way to reduce the risks associated with long-term use, and may improve cessation rates compared to usual care 8.
• Patients should be involved in developing a tapering plan and offered behavioral advice to help manage withdrawal symptoms and reduce the risk of relapse 8.