From the Guidelines
Benzodiazepines should be used for the shortest possible duration, ideally not exceeding 2-4 weeks, to minimize the risk of physical dependence, as recommended by the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guidelines 1. The general consensus is that benzodiazepines (benzos) may be safely given for about 2-4 weeks before physical dependence typically develops. After this period, patients are at increasing risk of developing tolerance, dependence, and withdrawal symptoms upon discontinuation. Common benzodiazepines include diazepam (Valium), alprazolam (Xanax), lorazepam (Ativan), and clonazepam (Klonopin). When prescribing these medications, it's essential to use the lowest effective dose for the shortest duration possible, as advised by the guidelines 1. If treatment beyond 2-4 weeks is necessary, careful monitoring and periodic reassessment of the need for continued therapy should be implemented. Physical dependence occurs because benzos enhance the effect of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. With prolonged use, the brain adapts to this enhanced inhibition by reducing natural GABA activity and increasing excitatory neurotransmission, leading to tolerance and dependence. When discontinuing benzodiazepines after extended use, a gradual tapering schedule is essential to minimize withdrawal symptoms, which can include anxiety, insomnia, irritability, and in severe cases, seizures. Some key points to consider when prescribing benzodiazepines include:
- Using the lowest effective dose for the shortest possible duration
- Careful monitoring and periodic reassessment of the need for continued therapy
- Counseling patients on the potential risks of benzodiazepine use, including physical dependence and withdrawal symptoms
- Avoiding the use of benzodiazepines in older adults and patients with respiratory conditions, sleep apnea, or neuromuscular diseases, due to the increased risk of adverse effects 1.
From the FDA Drug Label
The risk of dependence may increase with dose and duration of treatment The continued use of benzodiazepines, including clonazepam, may lead to clinically significant physical dependence Abrupt discontinuation or rapid dosage reduction of clonazepam after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening
The general consensus is that benzodiazepines may lead to physical dependence with prolonged use. However, the exact duration before physical dependence develops is not explicitly stated in the provided drug labels.
- Key factors that increase the risk of dependence include:
From the Research
Benzodiazepine Dependence
The general consensus is that benzodiazepines may be given for a short period before physical dependence develops. According to 4, benzodiazepine dependence could be prevented by adherence to recommendations for short-term prescribing, typically 2-4 weeks.
Factors Influencing Dependence
Several factors can influence the development of physical dependence on benzodiazepines, including:
- Dose and duration of use 5
- Frequency of dose interval 5
- Mode of discontinuation 5
- Pharmacologic characteristics of the benzodiazepine 5
- Personality and previous or concurrent use of cross-dependent drugs and/or alcohol 5
Guidelines for Prescribing Benzodiazepines
Guidelines for the clinical use of benzodiazepines recommend careful consideration of the potential for dependence and withdrawal 6. Principles of benzodiazepine selection are outlined for various psychiatric indications and diverse populations, including the elderly and drug and alcohol abusers 6.
Risks of Long-Term Use
Long-term use of benzodiazepines can result in physical dependence, tolerance, and withdrawal reactions 7, 8. The risk of dependence and withdrawal is higher with short- and intermediate-beta half-life compounds than with long-acting agents 6.
Management of Benzodiazepine Withdrawal
Management of benzodiazepine withdrawal typically involves gradual dosage tapering and psychological support when necessary 4. Cognitive behavioral therapy has shown the most benefit in terms of behavioral treatments for benzodiazepine discontinuation 7.