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.
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Comparison chart:
Clonazepam |
Diazepam | |
| 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
References
- 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: http://emedicine.medscape.com/article/1187334-overview
- 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
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