What are the implications of Benzodiazepine (BZD) dependence?

From the Guidelines

Benzodiazepine dependence should be managed with a gradual tapering schedule, reducing the dose by 25% every 1-2 weeks, to minimize withdrawal symptoms and ensure safe recovery. This approach is supported by the most recent and highest quality study, which emphasizes the importance of a gradual withdrawal strategy to minimize potential discontinuation effects 1. The Eliminating Medications Through Patient Ownership of End Results (EMPOWER) trial demonstrated success in tapering benzodiazepines in older adults, with 62% of patients expressing interest in benzodiazepine changes and 27% stopping benzodiazepines compared to 5% in the control group 1.

Key Considerations for Tapering Benzodiazepines

• Gradual reduction of the benzodiazepine dose to minimize withdrawal symptoms
• Reduction of the dose by 25% every 1-2 weeks, as suggested by the EMPOWER trial 1
• Consideration of safer alternatives, such as psychological or pharmacological treatments, including cognitive-behavioral therapy, problem-solving, and integrative strategies 1
• Importance of patient education and self-empowerment in the tapering process, as emphasized by the EMPOWER trial 1

Managing Withdrawal Symptoms

• Adjunctive medications, such as propranolol or antidepressants, may be used to manage physical and mood symptoms during tapering 1
• Psychological support through cognitive behavioral therapy is essential throughout the process 1
• Monitoring for potential discontinuation effects, such as rebound anxiety, hallucinations, seizures, and delirium tremens, and adjusting the tapering schedule as needed 1

Coordination of Care

• Communication with mental health professionals managing the patient to discuss the patient's needs, prioritize patient goals, and weigh risks of concurrent benzodiazepine and opioid exposure 1
• Involvement of pharmacists and pain specialists as part of the management team when opioids are co-prescribed with benzodiazepines 1

From the FDA Drug Label

Abuse, Misuse, and Addiction The use of benzodiazepines, including diazepam , exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death Dependence and Withdrawal Reactions To reduce the risk of withdrawal reactions, use a gradual taper to discontinue diazepam or reduce the dosage The continued use of benzodiazepines, including diazepam, may lead to clinically significant physical dependence Abrupt discontinuation or rapid dosage reduction of diazepam after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening

Benzodiazepine dependence is a significant risk associated with the use of diazepam. The continued use of diazepam may lead to clinically significant physical dependence. To minimize this risk, it is essential to:

• Assess each patient's risk for abuse, misuse, and addiction before prescribing diazepam and throughout treatment
• Use the lowest effective dosage and avoid concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction
• Gradually taper the dosage to discontinue diazepam or reduce the dosage to minimize the risk of withdrawal reactions 2, 2, 2

From the Research

Benzodiazepine Dependence

• Benzodiazepine dependence can occur as a result of treatment for anxiety disorders or sleep disturbance, and it is characterized by withdrawal symptoms on stopping treatment, including perceptual disturbances, epileptic seizures, weight loss, insomnia, and autonomic symptoms 3.
• The risk of benzodiazepine dependence is higher if the benzodiazepine has been taken in regular dosage for more than 4 months, higher dosages have been used, the drug is stopped suddenly, or a short-acting benzodiazepine has been taken 3.
• Gradual reduction of dosage is the best way to avoid the withdrawal syndrome, and temporary prescription of other drugs, particularly beta-adrenoceptor blocking drugs, may attenuate withdrawal symptoms 3.

Management of Benzodiazepine Dependence

• The management of benzodiazepine dependence involves either gradual benzodiazepine withdrawal or maintenance treatment, and prescribing interventions, substitution, psychotherapies, and pharmacotherapies can all contribute 4.
• It is helpful to switch to a long-acting benzodiazepine in both withdrawal and maintenance therapy, and the dose should be gradually reduced over weeks to lower the risk of seizures 4.
• Nonpharmacological treatment of the symptoms of withdrawal, such as anxiety or insomnia, is effective, and better outcomes are achieved where the GP discusses and plans strategies well in advance with the patient 5.

Pharmacological Interventions for Benzodiazepine Discontinuation

• Pharmacological interventions, such as valproate, tricyclic antidepressants, pregabalin, captodiame, paroxetine, and flumazenil, may facilitate benzodiazepine tapering and reduce symptoms of anxiety and benzodiazepine withdrawal 6.
• However, the evidence for these interventions is of low or very low quality, and more randomised controlled trials are required to draw firm conclusions regarding pharmacological interventions to facilitate benzodiazepine discontinuation in chronic benzodiazepine users 6.

Risk of Benzodiazepine Dependence

• The risk of benzodiazepine dependence is higher in patients who have been treated with benzodiazepines for at least two months and/or fulfill criteria for benzodiazepine dependence 7.
• Intentional abusers of benzodiazepines usually have other substance abuse problems, and benzodiazepines are usually a secondary drug of abuse-used mainly to augment the high received from another drug or to offset the adverse effects of other drugs 7.