What are the effects of long-term use of Lorazepam (Ativan, benzodiazepine)?

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From the Guidelines

Long-term use of lorazepam is generally not recommended beyond 2-4 weeks due to significant risks, including physical dependence, tolerance, and withdrawal symptoms, as well as potential adverse effects such as cognitive impairment, memory problems, and increased risk of falls. Lorazepam, a benzodiazepine medication commonly prescribed for anxiety and insomnia, can lead to these issues when used for extended periods. According to the American College of Physicians guideline on the management of chronic insomnia disorder in adults 1, there is insufficient evidence to evaluate the balance of the benefits and harms of long-term use of pharmacologic treatments, including lorazepam, in adults with chronic insomnia disorder.

Risks Associated with Long-Term Use

  • Physical dependence and tolerance
  • Withdrawal symptoms when stopped
  • Cognitive impairment and memory problems
  • Increased risk of falls, especially in older adults
  • Paradoxical reactions like increased anxiety or agitation

Recommendations for Use

If you've been taking lorazepam long-term, do not stop abruptly as this can trigger severe withdrawal symptoms, including seizures. Instead, work with your healthcare provider to develop a gradual tapering schedule, typically reducing the dose by 10-25% every 1-2 weeks. Alternative treatments for anxiety or insomnia should be considered, including:

  • Cognitive behavioral therapy
  • SSRIs for anxiety disorders
  • Non-benzodiazepine sleep medications

Importance of Gradual Tapering

Gradual tapering is crucial to minimize the risk of withdrawal symptoms and seizures. The FDA recommends that patients with insomnia that does not remit within 7 to 10 days of treatment should be further evaluated 1. Additionally, observational studies have shown that hypnotic drugs, including benzodiazepines like lorazepam, may be associated with infrequent but serious adverse effects, such as dementia, serious injury, and fractures 1.

From the FDA Drug Label

The continued use of benzodiazepines, including lorazepam may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Lorazepam oral concentrate can cause physical dependence and withdrawal reactions. Do not suddenly stop taking lorazepam oral concentrate Stopping lorazepam oral concentrate suddenly can cause serious and life-threatening side effects, including, unusual movements, responses or expressions, seizures, sudden and severe mental or nervous system changes, depression, seeing or hearing things that others do not see or hear, an extreme increase in activity or talking, losing touch with reality, and suicidal thoughts or actions Physical dependence is not the same as drug addiction.

The effects of long-term use of Lorazepam include:

  • Physical dependence: The risk of physical dependence increases with longer treatment duration and higher daily dose.
  • Withdrawal reactions: Stopping lorazepam suddenly can cause serious and life-threatening side effects.
  • Dependence and addiction: The use of benzodiazepines, including lorazepam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death 2, 2. It is not known if lorazepam oral concentrate is safe and effective for use for longer than 4 months 2.

From the Research

Effects of Long-Term Use of Lorazepam

The long-term use of lorazepam, a benzodiazepine, can have several effects on individuals, including:

  • Tolerance, dependence, and withdrawal effects, which can become major disadvantages 3
  • Adverse effects on cognitive performance, particularly memory, in elderly long-term users 4
  • Psychomotor impairment, especially in the elderly 3
  • Paradoxical excitement in some cases 3

Clinical Characteristics of Long-Term Users

Studies have shown that long-term users of lorazepam tend to:

  • Use low therapeutic doses of medication 5
  • Maintain their initial daily dose over time or decrease it 5
  • Shift their use of medication from an as-prescribed to an as-needed pattern 5
  • Have clinically important past and current psychiatric histories, including anxiety disorders and personality disorders 5

Pharmacokinetics and Safety

The pharmacokinetics of extended-release lorazepam have been characterized in phase 1 clinical studies, showing:

  • Steady-state bioequivalence with immediate-release lorazepam 6
  • Bioequivalence whether taken with or without food, administered intact or sprinkled onto food, or administered as intact 1 × 4- versus 4 × 1-mg capsules 6
  • No serious safety concerns were found in healthy adults 6

Clinical Pharmacology

Lorazepam has been shown to:

  • Produce anterograde amnesia reliably and for a relatively long duration 7
  • Have a duration of action that dictates it not be used in the outpatient setting or in patients with expected hospital stays less than 72 hours 7
  • Have most side effects associated with central nervous system depression, which are dose-related and fairly predictable 7

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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