What are alternative medications to lorazepam (Ativan) for a patient with anxiety or insomnia?

Alternative Medications to Lorazepam

For anxiety disorders, buspirone is the preferred alternative to lorazepam, offering similar efficacy without sedation, cognitive impairment, or dependence risk. 1, 2

Primary Alternatives by Clinical Indication

For Generalized Anxiety Disorder

• Buspirone (15-30 mg/day) is equally effective as lorazepam in reducing anxiety symptoms on standardized rating scales, but with significantly fewer sedative side effects (16% vs 65% experiencing drowsiness/lethargy/fatigue). 1, 2
• Buspirone lacks the hypnotic, anticonvulsant, and muscle relaxant properties of benzodiazepines, making it "anxioselective" and safer for daytime use. 2
• Important caveat: Buspirone has a 1-2 week lag time before anxiolytic effects begin, requiring patient counseling about delayed onset to maintain compliance. 2
• Unlike lorazepam, buspirone does not impair psychomotor or cognitive function and has no additive effects with alcohol, with limited potential for abuse and dependence. 2

For Insomnia

• Temazepam (7.5-30 mg at bedtime, start 7.5 mg in elderly) is the preferred benzodiazepine alternative for sleep-maintenance insomnia, with intermediate duration of action (6-8 hours) and no active metabolites. 3, 4
• Triazolam (0.125-0.25 mg) or zaleplon (5-10 mg at bedtime) are recommended for sleep-onset insomnia due to their short half-lives (<8 hours). 3
• Critical first-line approach: Cognitive behavioral therapy for insomnia (CBT-I) should be the initial intervention before any pharmacotherapy. 3

For Acute Agitation/Delirium

• Midazolam is preferred when immediate effect is required, with rapid onset (1-2 minutes IV) and short duration (15-80 minutes), making it ideal for acute situations. 3, 4
• The combination of a benzodiazepine plus an antipsychotic is frequently recommended for acutely agitated patients. 3

For Chemotherapy-Related Nausea/Vomiting

• Ondansetron (16 mg orally) plus dexamethasone (20 mg orally) is the guideline-recommended regimen for grade 3 emesis potential, replacing lorazepam as primary therapy. 5
• Granisetron (1 mg orally) plus dexamethasone (20 mg orally) is recommended for grade 4 emesis potential. 5
• Lorazepam (1 mg orally) is relegated to PRN adjunctive use only, not first-line therapy. 5

For Dyspnea in Advanced Cancer

• Morphine (2.5-5 mg orally every 4 hours in opioid-naïve patients) is first-line therapy for dyspnea palliation, with benzodiazepines reserved for non-response or insufficient response to opioids. 5
• Midazolam (2.5-5 mg subcutaneously every 4 hours or 10-30 mg/24 hours subcutaneously) is preferred over lorazepam when a benzodiazepine is needed for dyspnea. 5

Special Population Considerations

Elderly Patients

• All alternatives require dose reduction to 50% of standard adult doses in elderly patients due to increased sensitivity, fall risk, cognitive decline risk, and paradoxical agitation (occurring in ~10% of patients). 6, 3
• Agents with shorter half-lives and no active metabolites (lorazepam, oxazepam, temazepam) are preferred over long-acting agents like diazepam when benzodiazepines cannot be avoided. 3
• Avoid benzodiazepines entirely in elderly patients when possible; buspirone is the safest anxiolytic alternative. 3

Hepatic Impairment

• Lorazepam, oxazepam, and temazepam undergo glucuronidation (not hepatic oxidation), making them safer in liver disease compared to diazepam. 3, 4
• Buspirone is effective in mixed anxiety/depression and does not accumulate like long-acting benzodiazepines. 2

Renal Impairment

• Benzodiazepines have increased elimination half-life and prolonged clinical effects in renal failure, requiring dose reduction. 6

Critical Safety Warnings

Propylene Glycol Toxicity

• Parenteral lorazepam formulations contain propylene glycol, which can cause metabolic acidosis and acute kidney injury at IV doses as low as 1 mg/kg/day. 6
• An osmol gap >10-12 mOsm/L may identify significant propylene glycol accumulation. 6

Contraindications to All Benzodiazepines

• Severe pulmonary insufficiency, severe liver disease, and myasthenia gravis are absolute contraindications (except in moribund patients). 5
• Never combine benzodiazepines with opioids due to dangerous synergistic respiratory depression. 3, 4
• Extreme caution with concomitant high-dose olanzapine due to reported fatalities. 6

Duration of Use

• All benzodiazepines and alternatives should be used for the shortest duration possible, ideally no more than 2-4 weeks maximum, to minimize dependence, tolerance, and withdrawal risks. 3, 4
• Regular lorazepam use leads to tolerance, addiction, depression, and cognitive impairment. 6

Common Pitfalls to Avoid

• Do not use lorazepam chronically for insomnia: Studies show rebound insomnia on withdrawal is several times worse than the initial sleep improvement, with marked increases in daytime anxiety and tension. 7, 8
• Do not prescribe benzodiazepines without considering CBT-I first for insomnia patients. 3
• Do not use long-acting benzodiazepines (flurazepam, diazepam) in elderly patients due to accumulation of active metabolites causing prolonged sedation and delirium. 3, 4
• Do not abruptly discontinue benzodiazepines: Use gradual taper to prevent withdrawal symptoms including rebound insomnia, anxiety, tremor, and rarely seizures or psychosis. 6, 3