Comparison of Ativan (Lorazepam), Diazepam, and Klonopin (Clonazepam)
Lorazepam, diazepam, and clonazepam have distinct pharmacokinetic profiles that make each more suitable for specific clinical scenarios, with lorazepam being preferred for acute anxiety and insomnia due to its intermediate action, diazepam for muscle spasms due to its longer duration, and clonazepam for seizure disorders and panic disorder due to its longer half-life and sustained action.
Key Differences in Pharmacokinetics
Lorazepam (Ativan)
- Onset of action: 1-2 minutes IV; 15-30 minutes oral
- Duration: Intermediate-acting (15-80 minutes IV; 12-24 hours oral)
- Half-life: 10-20 hours
- Dosage range:
Diazepam
- Onset of action: 1-5 minutes IV; 30-60 minutes oral
- Duration: Long-acting (up to 24-48 hours due to active metabolites)
- Half-life: 20-100 hours (including active metabolites)
- Dosage range:
Clonazepam (Klonopin)
- Onset of action: 20-60 minutes oral
- Duration: Long-acting (18-50 hours)
- Half-life: 30-40 hours
- Dosage range:
Clinical Indications
Lorazepam (Ativan)
- Primary indications:
- Acute anxiety
- Short-term insomnia
- Status epilepticus
- Pre-procedure sedation
- Alcohol withdrawal
Diazepam
- Primary indications:
- Anxiety disorders
- Muscle spasms
- Alcohol withdrawal
- Adjunctive therapy for seizures
- Acute stress reactions 5
Clonazepam (Klonopin)
- Primary indications:
- Seizure disorders (especially absence and myoclonic seizures)
- Panic disorder
- Long-term anxiety management
- Certain movement disorders
Clinical Decision Algorithm
When to choose Lorazepam:
- For acute anxiety requiring rapid but not immediate relief
- For insomnia when intermediate duration is desired
- For elderly patients (fewer active metabolites)
- For patients with hepatic impairment
- For status epilepticus requiring IV administration
When to choose Diazepam:
- For muscle spasms
- For alcohol withdrawal
- When longer duration of action is needed
- For episodic anxiety with intermittent dosing 5
- When oral or IV administration options are needed
When to choose Clonazepam:
- For seizure disorders requiring long-term management
- For panic disorder (specifically indicated at lower doses) 4
- When once or twice daily dosing is preferred for compliance
- For patients who develop tolerance to shorter-acting benzodiazepines
Important Considerations and Cautions
All benzodiazepines:
- Risk of tolerance, dependence, and withdrawal with prolonged use
- Respiratory depression, especially when combined with other CNS depressants
- Increased risk of falls and cognitive impairment in elderly
- Paradoxical reactions in approximately 10% of patients 2
- Should be tapered gradually when discontinuing
Specific cautions:
- Lorazepam: May cause more pronounced amnesia
- Diazepam: More likely to cause sedation due to active metabolites
- Clonazepam: May require more careful monitoring for depression
Comparative Efficacy
- In status epilepticus, clonazepam has shown better clinical symptom control compared to lorazepam in some studies 6
- Lorazepam is frequently underdosed in clinical practice 6
- For alcohol abstinence maintenance, benzodiazepines are not first-line therapy 2
Remember that benzodiazepines should generally be prescribed for short-term use (ideally ≤4 weeks) to minimize risks of dependence and tolerance 5. For long-term anxiety management, non-benzodiazepine alternatives should be considered first.