Clonazepam (Klonopin®) versus Diazepam (Valium®)

Based on "Essential Psychopharmacology"
written by Stephen M. Stahl, MD, PhD

Difference between Clonazepam and Diazepam

Both clonazepam and diazepam are long-acting benzodiazepines. Two benzodiazepines differ in their effects on GABA-A receptors, route of metabolism, and elimination half-life.


Comparison chart:

Brand name/Year of initial approval Klonopin®, 1975 Valium®, 1963
Formulations Oral tablets, oral disintegrating wafers Oral tablets, oral solution, intramuscular, injectable solution, rectal gel
Legal status Schedule IV
Controlled substance
Drug class Benzodiazepine, long acting
FDA-approved Indications • Panic disorder
• Lennox-Gastaut syndrome
• Akinetic seizure
• Myoclonic seizure
• Acute mania
• Acute psychosis
• Anxiety disorder
• Symptoms of anxiety
• Alcohol withdrawal
• Skeletal muscle spasms and spasticity
• Adjunctively in convulsive disorders
• Anxiety relief prior to cardioversion
Off-label uses • Insomnia5
• Restless legs syndrome6 • Anesthetic premedication7
Mechanism of action • Prominent anticonvulsant activity
• Anxiolytic, sedative, muscle-relaxant effects
Benzodiazepines work by facilitation of the action of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS.

Clonazepam has higher affinity for the GABA-A receptor site than diazepam2. Clonazepam is 10–20 times more potent than diazepam.
Clonazepam has more selective anticonvulsant activity8. • I.V. diazepam produces analgesia
• Decreases gastric acid secretion during the night and prevents stress ulcers
Half-life 30-40 hours 20-50 hours (mean half-life 48 hours)
Oral bioavailability 90% ~100%
Metabolism, Elimination Clonazepam is metabolized in the liver by CYP3A4. The drug is metabolized principally by reduction of the nitro group to produce inactive 7-amino derivatives. Less than 1% of the drug is excreted unchanged in the urine. Metabolized by CYP2C19 and CYP3A4 to an active metabolite desmethyldiazepam.
Diazepam and its metabolites are excreted mainly in the urine, principally as their glucuronide conjugates.
Contraindications • History of sensitivity to benzodiazepines
• Hypersensitivity to diazepam
• Children under 6 months of age
• Myasthenia gravis
• Severe respiratory insufficiency
• Sleep apnea
• Acute narrow angle glaucoma
• Significant liver disease
Warnings & precautions • Abuse, physical dependence, tolerance
• Impairment of cognitive and motor skills9
• Abnormal thinking or behavioral changes
Side effects • Drowsiness
• Sedation
• Somnolence
• Ataxia
• Fatigue
• Depression
• Incoordination
• Hypersalivation
• Hypotension
Drug interactions • Increased depressive effects when taken with other CNS depressants or alcohol
Pregnancy category D
Onset of effect Rapid onset of action, 1-5 min. Both benzodiazepines are highly lipid-soluble and penetrate rapidly into the brain.
Advantages • Broad anti-seizure properties
• One of the most useful benzodiazepines for preventing recurrent seizures1
• Has a role in long-term treatment of epilepsy
• The first choice for emergency management of convulsions, e.g. status epilepticus, tetanus, eclampsia, convulsant drug poisoning, ongoing acute seizures.
• Various dosage formulations allow more flexibility of administration
Disadvantages   • Rapid development of tolerance to the antiepileptic effect3. Not useful as an oral anticonvulsant.
Both drugs are quickly redistributed to lipid stores. This may cause recurrence of seizures, and necessitate co-administration of a long-acting anticonvulsant.

In contrast to diazepam, which is used mainly for treatment of acute seizures, clonazepam is also useful for long-term treatment of refractory, chronic epilepsy.

Experimental epilepsy

Clonazepam is superior to diazepam in suppressing focal seizures and focal spiking4.

Further reading


  • 1. C.P. Panayiotopoulos The Epilepsies: Seizures, Syndromes and Management. Ch.14 Pharmacopoeia of Prophylactic Antiepileptic Drugs. Oxford , U.K. , 2005
  • 2. Juan G. Ochoa, Selim R. Benbadis. Antiepileptic Drugs. Available at:
  • 3. Rosenberg HC, Tietz EI, Chiu TH. Tolerance to anticonvulsant effects of diazepam, clonazepam, and clobazam in amygdala-kindled rats. Epilepsia. 1989 May-Jun;30(3):276-85. PubMed
  • 4. van Duijn H. Superiority of clonazepam over diazepam in experimental epilepsy. Epilepsia. 1973 Jun;14(2):195-202.
  • 5. Sastre Hernández MS, Hentschel HD, Fichte K. Comparative efficacy of lormetazepam (Noctamid) and diazepam (Valium) in 100 out-patients with insomnia. J Int Med Res. 1981;9(3):199-202. PubMed
  • 6. Montagna P, Sassoli de Bianchi L, Zucconi M, Cirignotta F, Lugaresi E. Clonazepam and vibration in restless legs syndrome. Acta Neurol Scand. 1984 Jun;69(6):428-30.
  • 7. Dionne RA, Goldstein DS, Wirdzek PR. Effects of diazepam premedication and epinephrine-containing local anesthetic on cardiovascular and plasma catecholamine responses to oral surgery. Anesth Analg. 1984 Jul;63(7):640-6.
  • 8. Voronina TA, von Littrow K. Comparative experimental characteristics of clonazepam and diazepam. Farmakol Toksikol. 1980 May-Jun;43(3):296-9. PubMed
  • 9. Gagnon MA, Langlois Y, Boghen DR, Verdy M. Effects of halazepam and diazepam on the motor coordination of geriatric subjects. Eur J Clin Pharmacol. 1977 Jul 19;11(6):443-8.

Published: December 02, 2016
Last updated: May 15, 2017


More Comparisons
Home | Contact Us | Cookies Policy

This website is certified by Health On the Net Foundation. Click to verify. This site complies with the HONcode standard for trustworthy health information: verify here

Copyright © 2007-2019 All rights reserved.
All information is for educational purposes only.