What are the effects of chronic use of lorazepam (Ativan)?

Chronic Use of Lorazepam: Significant Risks and Clinical Considerations

Chronic lorazepam use leads to tolerance, physical dependence, cognitive impairment, and increased risk of falls, particularly in older adults, and should be avoided for long-term management whenever possible. 1

Critical Safety Warnings

The FDA mandates boxed warnings for lorazepam regarding three major risks with chronic use 2:

• Physical dependence and withdrawal: Continued use leads to clinically significant physical dependence, with risks increasing with longer treatment duration and higher daily doses 2
• Abuse, misuse, and addiction: Chronic use exposes patients to risks of addiction, which can lead to overdose or death 2
• Life-threatening withdrawal reactions: Abrupt discontinuation after chronic use may precipitate acute withdrawal reactions including seizures, severe mental status changes, delirium, and potentially death 2

Cognitive and Neurological Effects

Chronic benzodiazepine use, including lorazepam, causes persistent cognitive dysfunction that does not fully resolve even after discontinuation. 3

• Impaired cognitive domains: Long-term use impairs visuospatial ability, processing speed, verbal learning, and memory function 3
• Incomplete recovery: Meta-analyses demonstrate that while cognitive function improves after benzodiazepine withdrawal, patients do not return to the performance levels of benzodiazepine-free controls 3
• Acute effects persist in chronic users: Even elderly patients on long-term lorazepam therapy (≥3 months) continue to experience significantly poorer recall and slowed psychomotor performance following each dose 4
• Depression and cognitive impairment: Regular use can lead to depression and cognitive impairment beyond the acute dosing effects 1

Risks in Older Adults

Lorazepam poses particularly severe risks in elderly populations and should be tapered or avoided according to Beers Criteria. 1

Specific geriatric complications include 1:

• Falls and injuries: Sedation, cognitive impairment, and unsafe mobility leading to injurious falls
• Motor skill impairment: Decreased coordination and balance
• Habituation: Development of tolerance requiring dose escalation
• Withdrawal syndromes: Including severe sleep disruption when attempting discontinuation
• Paradoxical reactions: Approximately 10% of patients experience paradoxical agitation, anxiety, excitation, hostility, or aggression 1, 2

Adverse Effects Profile

Common adverse reactions with chronic use include 2:

• Sedation (15.9% incidence) - most frequent adverse effect
• Dizziness (6.9%)
• Weakness (4.2%)
• Unsteadiness (3.4%) - increases with age
• Respiratory depression: Can worsen sleep apnea and obstructive pulmonary disease 2
• Ataxia and extrapyramidal symptoms 2

Clinical Patterns in Long-Term Users

Research on chronic therapeutic users reveals important patterns 5:

• Most patients maintain or decrease their initial dose over time (mean lorazepam dose: 2.7 mg/day) 5
• Patients shift from scheduled to as-needed dosing patterns 5
• 47% have concurrent anxiety disorders, most commonly generalized anxiety 5
• 45% have diagnosable personality disorders, most commonly obsessive-compulsive personality disorder 5
• Many chronic users represent appropriate maintenance therapy for chronic psychiatric conditions rather than addiction 5

Special Populations and Contraindications

In patients with liver disease, lorazepam requires careful dose adjustment despite being an intermediate-acting benzodiazepine. 1

• Contrary to widespread belief, metabolism of all benzodiazepines, including lorazepam, is affected by hepatic insufficiency 1
• In cirrhotic patients, over 70% may not require pharmacological treatment for alcohol withdrawal, challenging routine benzodiazepine use 1
• When used in decompensated liver disease, prioritize symptom-adapted dosing with the lowest effective dose 1

Appropriate Clinical Uses

Lorazepam has limited appropriate indications 1:

• Short-term management of insomnia, anxiety, and agitation (not chronic use) 1
• Alcohol or benzodiazepine withdrawal: Treatment of choice as monotherapy 1
• Crisis intervention: Severe agitation in delirium when patient poses risk to self or others (0.25-0.5 mg in elderly/frail patients) 1
• Infrequent, low doses of short half-life agents are least problematic 1

Deprescribing Recommendations

The EMPOWER approach and Beers Criteria recommend tapering lorazepam whenever possible, with consideration of safer alternatives. 1

For anxiety and sleep 1:

• Implement gradual taper technique to avoid life-threatening withdrawal 2
• Consider cognitive behavioral therapy as safer alternative 1
• Use non-pharmacological interventions and adjuncts 1
• Reassess need for medication regularly, especially when perceived lack of benefit 1

Critical pitfall: Never abruptly discontinue lorazepam after chronic use - withdrawal can cause seizures, severe mental status changes, and death. 2 Always use gradual dose reduction over weeks to months depending on duration of use and dose.