What are the recommended dosing regimens of Ativan (lorazepam) for anxiety, insomnia, and acute seizure clusters in adults, and how should the dose be modified for elderly patients, hepatic impairment, or a history of substance use disorder?

Ativan (Lorazepam): Dosing, Indications, and Special Populations

Anxiety Management

For anxiety disorders in adults, lorazepam is typically dosed at 0.02–0.04 mg/kg (maximum 2 mg per dose) as needed, or 0.02–0.06 mg/kg every 2–6 hours for continuous management, with a maximum infusion rate of 10 mg/hr. 1

• In elderly or debilitated patients, start with lower doses and titrate gradually, as this population is significantly more sensitive to benzodiazepine effects 1
• For pre-operative anxiety, lorazepam 2.5 mg orally the evening before surgery, followed by an intramuscular injection 90 minutes before anesthesia (dose adjusted to body weight) provides effective anxiolysis with minimal side effects 2
• Caution: Regular use leads to tolerance, addiction, depression, and cognitive impairment; paradoxical agitation occurs in approximately 10% of elderly patients treated with benzodiazepines 1

Insomnia Treatment

Lorazepam at 2 mg nightly is moderately effective for sleep induction and maintenance initially, but continued use results in tolerance, daytime anxiety, and marked rebound insomnia upon withdrawal. 3

• Peak withdrawal sleep disturbance (occurring on the third night after discontinuation) is several times greater than the peak degree of sleep improvement achieved during active treatment 3
• Benzodiazepines should not be first-line for insomnia management; infrequent, low doses of agents with short half-lives are least problematic 1
• Alternative agents such as ramelteon (for sleep initiation) or trazodone (25–200 mg) are preferred for chronic insomnia, particularly in elderly patients 1

Acute Seizure Clusters

For acute seizure management, lorazepam has been used off-label in the USA, though it is not FDA-approved specifically for seizure clusters. 4

• FDA-approved alternatives for seizure clusters include diazepam rectal gel (≥2 years), midazolam nasal spray (≥12 years), and diazepam nasal spray (≥6 years) 4
• In the European Union, lorazepam is indicated for anxiety rather than seizure management 4

Agitation and Delirium in Critical Care

In ICU settings, lorazepam is dosed at 0.02–0.04 mg/kg (≤2 mg) as needed, or 0.01–0.1 mg/kg/hr continuous infusion (≤10 mg/hr), but carries significant risks including propylene glycol toxicity. 1

• Lorazepam formulations contain propylene glycol as a diluent, which can cause metabolic acidosis and acute kidney injury in critically ill patients 1
• Benzodiazepines should NOT be used as initial treatment for delirium in patients not already taking them 1
• For severe delirium with agitation refractory to high-dose neuroleptics, lorazepam may be added only after therapeutic levels of antipsychotics are established to prevent paradoxical excitation 1

Elderly Patients: Critical Modifications

Elderly patients require substantially lower doses due to increased sensitivity to sedative effects, with starting doses of 0.25–0.5 mg orally (maximum 2 mg in 24 hours). 5

• Avoid benzodiazepines as first-line for agitation in elderly patients with dementia—they increase delirium incidence and duration, cause paradoxical agitation in 10% of cases, and increase fall risk 1, 5
• Lorazepam elimination half-life and duration of clinical effect are increased in patients with renal failure 1
• For elderly patients with insomnia or anxiety in dementia, SSRIs (citalopram 10–40 mg or sertraline 25–200 mg) are preferred first-line agents 1, 5

Hepatic Impairment

Lorazepam clearance is reduced in patients with hepatic dysfunction, requiring dose reduction and extended dosing intervals. 1

• Unlike midazolam and diazepam, lorazepam has no active metabolites that accumulate with renal dysfunction, making it relatively safer in combined hepatic-renal impairment 1
• Lorazepam has been reported to cause drug-induced liver injury, presenting as cholestatic hepatitis with jaundice and pruritus 6
• Monitor liver enzymes if prolonged use is necessary in patients with pre-existing hepatic disease 6

Substance Use Disorder History

Patients with a history of substance use disorders should avoid lorazepam due to high addiction potential; ramelteon is preferred for sleep initiation difficulties as it is not a DEA-scheduled drug. 1

• Regular benzodiazepine use leads to tolerance and addiction, with withdrawal symptoms including rebound anxiety and insomnia 1, 3
• If benzodiazepines must be discontinued in patients with substance use history, taper gradually over 10–14 days to limit withdrawal symptoms 1

Critical Safety Warnings

• Respiratory depression and systemic hypotension occur especially when lorazepam is combined with opioids or other cardiopulmonary depressants 1
• Benzodiazepine-induced cardiopulmonary instability is more likely in critically ill patients with baseline respiratory insufficiency or cardiovascular instability 1
• Memory impairment and confusion can occur even at therapeutic doses 3
• Discontinuing lorazepam after prolonged use results in marked rebound insomnia (peak on night 3) and increased daytime anxiety and tension 3

When NOT to Use Lorazepam

• First-line treatment for agitated delirium in elderly patients (except alcohol or benzodiazepine withdrawal) 5
• Routine management of insomnia or anxiety in dementia patients 1, 5
• As monotherapy for delirium without established antipsychotic coverage 1
• Patients with severe respiratory insufficiency or unstable cardiovascular status without close monitoring 1