What is the recommended dosage of benzodiazepines (BZDs), such as alprazolam (Xanax) or clonazepam (Klonopin), for anxiety and insomnia?

Benzodiazepine Dosing for Anxiety and Insomnia

For anxiety and insomnia, start with the lowest effective dose: alprazolam 0.25 mg 2-3 times daily (or 0.5 mg for acute crisis) in elderly/debilitated patients, or 0.5-1.0 mg three times daily in younger adults, with short-acting agents like lorazepam, oxazepam, or temazepam preferred for infrequent use to minimize tolerance and cognitive impairment. 1, 2

Initial Dosing Strategy

For Elderly or Debilitated Patients

• Start with alprazolam 0.25 mg orally 2-3 times daily for anxiety disorders 2
• For acute anxiety crisis, may use 0.25-0.5 mg orally 3 times daily, beginning the night before anticipated stressor 1
• The FDA mandates this lower starting dose due to heightened sensitivity to benzodiazepine effects in elderly populations 2

For Younger, Healthy Adults

• Alprazolam 0.5 mg three times daily is the typical starting dose for anxiety 3
• Maximum recommended dose is 4 mg/day in divided doses 2, 4
• Distribute doses evenly throughout waking hours (three or four times daily schedule) to minimize interdose symptoms 2

For Insomnia Specifically

• Use short-to-medium acting agents: temazepam, loprazolam, lormetazepam, or triazolam 1, 5
• Dosage varies by specific agent, but infrequent, low doses of agents with short half-life are least problematic 1
• Prescriptions should be limited to a few days, occasional use, or courses not exceeding 2 weeks 5

Critical Dosing Principles

Duration of Treatment

• Limit courses to 4 weeks maximum to prevent tolerance and dependence 5
• For panic disorder, therapy should continue until substantial reduction in attacks is achieved, but periodic reassessment for dose reduction is advised for patients on >4 mg/day 2
• After extended freedom from symptoms, attempt carefully supervised tapered discontinuation 2

Dose Distribution

• Alprazolam achieves peak levels in 0.7-2.1 hours with a half-life of 12-15 hours, requiring multiple daily doses 3
• For panic disorder specifically, maximum 2 mg/day of any high-potency benzodiazepine when given for more than 1 week is recommended 4

Discontinuation Protocol

Never abruptly discontinue benzodiazepines due to severe withdrawal risk 2, 6

FDA-Approved Taper Schedule

• Decrease daily dosage by no more than 0.5 mg every 3 days 2
• Some patients require even slower reduction 2
• If significant withdrawal symptoms develop, reinstitute previous dosing schedule and attempt slower taper only after stabilization 2
• In controlled studies, patients on >4 mg/day successfully tapered to 50% of maintenance dose without loss of clinical benefit 2

Withdrawal Syndrome Timeline

• Rebound anxiety and insomnia occur within 1-4 days of discontinuation, depending on drug half-life 6
• Full withdrawal syndrome typically lasts 10-14 days 6
• Withdrawal is particularly difficult with alprazolam and may be associated with serious rebound symptoms 7

Major Safety Warnings

High-Risk Populations

• Elderly patients experience higher plasma concentrations due to reduced clearance 8
• Major risks include psychomotor impairment, falls, cognitive impairment, and paradoxical agitation (occurs in ~10% of patients) 1, 8
• Regular use leads to tolerance, addiction, depression, and cognitive impairment 1

Specific Contraindications and Cautions

• Avoid in patients with obstructive sleep apnea (clonazepam 0.5-1.0 mg can worsen apnea) 1
• Use with caution in patients with liver disease 1
• Never combine with other CNS depressants or alcohol due to additive psychomotor impairment 8
• Risk of confusion and falls at higher doses (clonazepam 2.0 mg), with potential for subdural hematoma 1

Alternative Benzodiazepines by Indication

For Anxiety

• Diazepam is usually the drug of choice for anxiety, given in single doses or very short courses (1-7 days) or short courses (2-4 weeks) 5
• Lorazepam and oxazepam are alternatives with no active metabolites 1

For Panic Disorder

• Alprazolam and clonazepam have similar positive effects in controlled trials 7
• Clonazepam permits less frequent dosing due to longer half-life, though ~20% experience unacceptable sedation 7
• Diazepam and lorazepam have also been effective 7

For REM Sleep Behavior Disorder

• Clonazepam 0.25-2.0 mg 30 minutes before bedtime (doses up to 4.0 mg reported) 1
• Women may require higher dosing (1.4 ± 0.4 mg) than men (0.68 ± 0.4 mg) 1

Clinical Pitfalls to Avoid

• High-potency, short-acting agents like triazolam carry greater risks of adverse effects 5
• Alprazolam is not recommended in the UK for long-term use despite widespread U.S. use 5
• Discontinuation of alprazolam is particularly difficult compared to other benzodiazepines 7
• Dose escalation and tolerance are rare but can occur, particularly with longer treatment duration 1
• Memory impairment and discontinuation syndrome are common clinical issues with all benzodiazepines 4