What are the recommendations for long-term low-dose benzodiazepine (BZD) use?

Long-Term Low-Dose Benzodiazepine Use: Risks and Recommendations

Long-term low-dose benzodiazepine use is generally not recommended due to risks of dependence, cognitive impairment, and withdrawal symptoms, even at therapeutic doses. 1

Risks Associated with Long-Term Use

• Regular use of benzodiazepines can lead to tolerance, addiction, depression, and cognitive impairment, even at low doses 1
• Approximately 10% of patients may experience paradoxical agitation with benzodiazepine treatment 1
• Long-term benzodiazepine use is associated with cognitive dysfunction in multiple domains, including visuospatial ability, speed of processing, and verbal learning 2
• Even after discontinuation of benzodiazepines, cognitive function may not return to levels matching benzodiazepine-free controls 2
• Physical dependence can develop with therapeutic doses, manifesting as withdrawal symptoms upon abrupt discontinuation 3
• Long-term use (>6 months) even at low therapeutic doses can produce a prolonged, subacute withdrawal syndrome when discontinued 4

Types of Dependence

• It's important to distinguish between addiction and normal physical dependence on benzodiazepines 3:
  • Physical dependence: A predictable adaptation of the body to the presence of benzodiazepines, can occur with therapeutic doses 3
  • Addiction: Intentional abuse, usually seen in patients with other substance abuse problems 3
• Low-dose dependency without dose escalation is common in older patients using benzodiazepines long-term 5

Recommendations for Use

• Benzodiazepines should generally be limited to:
  • Single doses for acute stress reactions 6
  • Very short courses (1-7 days) 6
  • Short courses (2-4 weeks) 6
  • Only rarely for longer-term treatment 6
• If prescribed for insomnia:
  • Limit prescriptions to occasional or intermittent use 6
  • Courses should not exceed 2 weeks 6
  • Administration on an empty stomach is advised to maximize effectiveness 1

Medication Selection

• For short-term insomnia treatment, benzodiazepines with medium duration of action such as temazepam are suitable 6
• For anxiety, diazepam is often the drug of choice for short-term use 6
• Benzodiazepines not specifically approved for insomnia (e.g., lorazepam, clonazepam) might be considered if the duration of action is appropriate for the patient's presentation 1
• Short-acting benzodiazepines with shorter half-lives are generally preferred to minimize risk of adverse effects 1

Special Populations

• In elderly patients, those with advanced liver disease, or debilitating conditions:
  • Lower starting doses are recommended (e.g., 0.25 mg for alprazolam) 7
  • Increased sensitivity to benzodiazepine effects is common 7
  • Higher risk of falls and cognitive impairment 1
• Benzodiazepines are not recommended during pregnancy or nursing 1
• Caution is advised if signs/symptoms of depression, compromised respiratory function, or hepatic heart failure are present 1

Discontinuation

• Abrupt discontinuation should always be avoided due to risk of withdrawal symptoms 7
• Recommended tapering schedule:
  • Reduce dose by no more than 0.5 mg every 3 days 7
  • Some patients may require an even more gradual discontinuation 7
  • If significant withdrawal symptoms develop, reinstate previous dosing schedule and stabilize before attempting a slower taper 7
• Withdrawal symptoms may include heightened sensory perception, impaired concentration, dysosmia, clouded sensorium, paresthesias, muscle cramps, muscle twitching, diarrhea, blurred vision, decreased appetite, and weight loss 7

Alternative Approaches

• For chronic insomnia, cognitive behavioral therapy for insomnia (CBT-I) should be considered as first-line treatment 1
• For anxiety, benzodiazepines should generally be used in conjunction with other measures like psychological treatments or antidepressants 6
• For insomnia, consider non-benzodiazepine options such as:
  • Melatonin receptor agonists (e.g., ramelteon) 1
  • Low-dose doxepin (3-6 mg) 1
  • Non-benzodiazepine BZRAs (e.g., zolpidem, zaleplon, eszopiclone) at lowest effective doses for shortest duration 1

Monitoring

• Regular reassessment of continued need for benzodiazepines is essential 7
• For patients receiving doses greater than 4 mg/day, periodic reassessment and consideration of dosage reduction is advised 7
• Monitor for signs of cognitive impairment, especially in elderly patients 1, 2
• Be alert for development of tolerance or dependence 3