When should lorazepam (Ativan) not be used for alcohol withdrawal in patients with a history of paradoxical reactions to benzodiazepines (BZDs), severe respiratory depression, pregnancy, breastfeeding, elderly patients, substance abuse, severe liver disease, or a history of seizures?

When Lorazepam Should Not Be Used for Alcohol Withdrawal

Lorazepam should be avoided in alcohol withdrawal when patients have severe hepatic insufficiency/encephalopathy, severe respiratory compromise (COPD, sleep apnea), paradoxical reactions to benzodiazepines, or when intramuscular administration is the only route available. 1, 2, 3

Absolute Contraindications

Severe Hepatic Disease with Encephalopathy

• The FDA label explicitly states that lorazepam may worsen hepatic encephalopathy and should be used with caution in patients with severe hepatic insufficiency and/or encephalopathy. 2
• While lorazepam undergoes glucuronidation (theoretically safer in liver disease), clinical guidelines emphasize that benzodiazepines as a class should be used with extreme caution in severe liver disease. 1
• When hepatic dysfunction is suspected, switching to lorazepam from long-acting agents may be considered, but this applies to mild-moderate liver disease, not severe hepatic insufficiency with encephalopathy. 4

Severe Respiratory Depression

• Lorazepam is contraindicated in patients with severe pulmonary insufficiency. 1
• The FDA label mandates caution in patients with compromised respiratory function including COPD and sleep apnea syndrome. 2
• Lower doses (0.25-0.5 mg) must be used if administration is unavoidable in patients with COPD, but severe respiratory compromise remains a relative contraindication. 1

Paradoxical Reactions

• If paradoxical reactions occur (agitation, anxiety, insomnia rather than sedation), lorazepam should be discontinued immediately. 2
• Paradoxical reactions are more likely in children and elderly patients. 2
• A documented case report from 2023 describes paradoxical excitation with intravenous lorazepam during alcohol withdrawal treatment, emphasizing the importance of recognizing and discontinuing the agent. 5
• The FDA label states that lorazepam may cause paradoxical agitation, and the ESMO guidelines note this as a known adverse effect. 1

Intramuscular Route Only Available

• When intramuscular administration is the only option, lorazepam should NOT be used—midazolam should be used instead for rapid symptom control. 3
• Lorazepam's lipophilicity results in slow and erratic absorption via the intramuscular route. 3
• The subcutaneous injection of lorazepam may cause local irritation. 1

Relative Contraindications Requiring Extreme Caution

Elderly and Debilitated Patients

• Elderly patients are more susceptible to sedative effects and should have initial doses not exceeding 2 mg, with frequent monitoring and careful dose adjustment. 2
• Use lower doses (0.25-0.5 mg) in older or frail patients, especially when co-administered with antipsychotics. 1
• Increased risk of falls is a significant concern in elderly patients receiving lorazepam. 1

Myasthenia Gravis

• Benzodiazepines including lorazepam should be used with caution in patients with myasthenia gravis (unless the patient is imminently dying). 1

Pregnancy and Breastfeeding

• The FDA label warns that lorazepam may harm the unborn baby, and patients should not breastfeed while taking lorazepam as it passes into breast milk. 2

History of Substance Abuse

• The FDA label emphasizes that lorazepam carries risks of abuse, misuse, and addiction even at recommended doses, particularly in patients with a history of drug or alcohol abuse. 2
• Benzodiazepines should not be continued beyond 10-14 days due to abuse potential. 4

Depression with Suicidal Ideation

• In patients with depression, benzodiazepines should not be used without adequate antidepressant therapy due to suicide risk. 2

Critical Clinical Context: When Lorazepam May Actually Be Preferred

Despite these contraindications, it's important to note that lorazepam is specifically recommended over long-acting benzodiazepines when hepatic dysfunction is suspected (mild-moderate, not severe with encephalopathy), as it undergoes glucuronidation rather than hepatic oxidation. 4, 6, 7

A 2009 randomized trial demonstrated that lorazepam (8 mg/day) was as effective as chlordiazepoxide (80 mg/day) in treating uncomplicated alcohol withdrawal, with similar safety profiles. 6

However, a 2017 comprehensive review argues that diazepam should be preferred over lorazepam for most alcohol withdrawal cases due to its faster time to peak effect, longer half-life providing smoother self-tapering withdrawal, and lower incidence of breakthrough symptoms. 3

Common Pitfalls to Avoid

• Do not assume lorazepam is automatically safer in all liver disease—severe hepatic insufficiency with encephalopathy remains a contraindication. 1, 2
• Do not combine lorazepam with high-dose olanzapine—fatalities have been reported with concurrent use due to oversedation and respiratory depression. 1
• Do not use lorazepam as monotherapy beyond 10-14 days—physical dependence and withdrawal reactions can occur. 2
• Do not administer intramuscularly—absorption is unreliable. 3