What are the recommended lorazepam (generic) doses for an adult without hepatic or renal impairment for anxiety and insomnia, how should dosing be adjusted for patients aged 65 years or older, and what are the contraindications, tapering recommendations, and alternative therapies?

Lorazepam Dosing and Management in Adults

Standard Dosing for Anxiety

For adults without hepatic or renal impairment, lorazepam should be initiated at 2–3 mg/day divided into 2–3 doses (typically 1 mg twice or three times daily), with the usual therapeutic range being 2–6 mg/day and a maximum of 10 mg/day. 1

• The largest dose should be taken at bedtime to minimize daytime sedation 1
• Dosage increases should be gradual, with evening doses increased before daytime doses 1
• For episodic or situational anxiety, lorazepam's shorter duration of action (half-life 8–15 hours) makes it preferable to longer-acting benzodiazepines like diazepam 2, 3

Standard Dosing for Insomnia

For insomnia due to anxiety or transient situational stress, a single dose of 2–4 mg at bedtime is recommended. 1

• Lorazepam may be considered when the duration of action is appropriate for the patient's sleep complaint, though cognitive behavioral therapy for insomnia (CBT-I) should be the initial intervention 3
• Short-acting benzodiazepines like lorazepam are more appropriate for sleep-onset insomnia, while intermediate-acting agents like temazepam are preferred for sleep-maintenance insomnia 3
• Critical caveat: A study found that lorazepam 1.5 mg at bedtime caused rebound anxiety and confusion the following morning, and withdrawal after 7 nights produced marked rebound insomnia on the third night—several times worse than the initial sleep improvement 4, 5

Dosing Adjustments for Patients ≥65 Years

Elderly or debilitated patients require an initial dosage of 1–2 mg/day in divided doses (typically 0.5 mg twice daily), adjusted as needed and tolerated, with a strict maximum of 2 mg/24 hours. 1, 6

• Start with half the standard adult dose for all elderly patients 3
• Elderly patients are significantly more sensitive to benzodiazepine effects, with substantially higher risks of falls, cognitive decline, delirium, and paradoxical agitation (occurring in approximately 10% of elderly patients) 7, 6
• Benzodiazepine clearance decreases with age, and the elimination half-life of lorazepam is increased in patients with renal failure 7
• The American Geriatrics Society Beers Criteria strongly advise against benzodiazepine use in patients aged ≥65 years due to cognitive impairment, increased delirium risk, and falls 7

Contraindications

Absolute contraindications to lorazepam include:

• Severe pulmonary insufficiency 6
• Severe liver disease (though reduced doses of 0.25 mg 2–3 times daily may be used in advanced liver disease with extreme caution) 6
• Myasthenia gravis (except in moribund patients) 6
• Acute narrow-angle glaucoma 1
• Known hypersensitivity to benzodiazepines 1

Relative contraindications and high-risk situations:

• Concomitant use with opioids or other CNS depressants due to dangerous synergistic respiratory depression 3
• Pregnancy and nursing 3
• Patients with depression, respiratory compromise, or hepatic/cardiac disease require extreme caution 3
• History of substance abuse due to high dependence risk 3

Tapering Recommendations

To reduce the risk of withdrawal reactions, lorazepam must be discontinued using a gradual taper rather than abrupt cessation. 1

• If withdrawal reactions develop (rebound insomnia, anxiety, tremor, rarely seizures or psychosis), pause the taper or increase back to the previous dose level, then decrease more slowly 1, 3
• Benzodiazepines should be used for the shortest duration possible, ideally no more than 2–4 weeks maximum 3, 2
• Withdrawal symptoms peak around the third night after discontinuation and can be several times worse than the original symptoms 4
• Long-term use is only justified when symptomatic relief and improved functioning clearly outweigh the risk of dependence 2

Alternative Therapies

For anxiety:

• Cognitive behavioral therapy (CBT) is the preferred first-line treatment before any pharmacologic intervention 3
• SSRIs (sertraline 25–50 mg/day or citalopram 10 mg/day) are the safest first-line pharmacologic options for chronic anxiety, with better tolerability and no dependence risk compared to benzodiazepines 8
• Environmental modifications, structured routines, and behavioral interventions should be attempted first 8

For insomnia:

• Cognitive behavioral therapy for insomnia (CBT-I) should be the initial intervention, not benzodiazepines 3
• Non-benzodiazepine hypnotics (zolpidem, zaleplon) may be considered, though they carry similar risks 7
• Sedating antidepressants (trazodone 25 mg/day, mirtazapine) are alternatives for refractory insomnia, particularly in patients with comorbid depression 7

Critical Safety Warnings

Propylene glycol toxicity: Parenteral lorazepam formulations contain propylene glycol, which can cause metabolic acidosis and acute kidney injury at total daily IV doses as low as 1 mg/kg 7, 6

Hepatotoxicity: Rare cases of drug-induced liver injury have been reported with lorazepam, requiring monitoring for jaundice, pruritus, or elevated liver enzymes 9

Dependence and tolerance: Regular use leads to tolerance, addiction, depression, and cognitive impairment 8, 3

Paradoxical reactions: Approximately 10% of patients, particularly elderly, experience paradoxical agitation rather than sedation 8, 6

Common Prescribing Pitfalls

• Do not prescribe lorazepam for chronic insomnia or anxiety beyond 2–4 weeks without compelling justification, as risks outweigh benefits 3, 6
• Do not combine with opioids or other CNS depressants due to fatal respiratory depression risk 3
• Do not use as first-line therapy in elderly patients (≥65 years) due to Beers Criteria warnings 7
• Do not abruptly discontinue after regular use, as withdrawal can be severe and dangerous 1, 4
• Do not exceed 2 mg/24 hours in elderly patients regardless of indication 1, 6