Clonazepam (Klonopin®)

Clonazepam in Brief
  • Generic name: Clonazepam
  • Brand names: Klonopin®
  • Therapeutic class: Anticonvulsant
  • Pharmacologic class: Benzodiazepine
  • FDA Approved: 1975
  • Pregnancy Category: D
  • Originally discovered: Hoffmann-La Roche, NJ, USA USA

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

FDA approved uses

  • Panic disorder
  • Lennox-Gastaut syndrome
  • Akinetic (atonic) seizure
  • Myoclonic seizure
  • Acute mania (adjunctive)
  • Acute psychosis (adjunctive)


Off-label uses & Therapeutic perspectives

  • Absence (petit mal) seizures
  • Restless leg syndrome 3 - clonazepam is the best studied benzodiazepine in restless legs syndrome.
  • Periodic limb movements in sleep2
  • REM sleep behaviour disorder 4
  • Bipolar disorder
  • Anxiety disorders 6
  • Social phobia 5
  • Tardive dyskinesia 7
  • Essential tremor 8
  • Burning mouth syndrome 9
  • Status epilepticus 10
  • Neurocardiogenic syncope 11
  • Tinnitus12
  • Sleep problems - beneficial especially in insomnia co-morbid with depression or restless legs syndrome
  • Burning mouth syndrome 11

Clonazepam for Insomnia & Sleep disturbances

Clonazepam is a potent anxiolytic with sedating propertiers due to its effects on GABA, the primary inhibitory neurotransmitter throughout the brain.

Many people with anxiety disorders experience insomnia as a consequence of the anxiety. So taking clonazepam to treat anxiety may also benefit sleep problems.

The main problem with clonazepam when it is used as a sleep aid is its very long half-life. As a result, when clonazepam is taken at bedtime, it causes next morning sedation, motor incoordination, and confusion.

It is better to use benzodiazepines with short half-lives for sleep problems. Short-acting benzodiazepines can help to fall asleep and stay asleep during the night without next morning hangover-like effects.

Nevertheless it looks like many patients successfully use clonazepam as a sleep aid.

Addition of clonazepam to fluoxetine in patients with major depression may improve sleep and promote greater improvement in depression symptoms13, 14.

Recent study has shown that clonazepam improves sleeping problems associated with major depression15.

Clonazepam Advantages

  • Low risk of tolerance development than with some other benzodiazepines16.
  • Half-life is considerably long and the drug can be dosed once or twice a day.
  • High therapeutic index.
  • Rapidity of action.
  • Clonazepam has broad anti-seizure properties and is one of the most potent antiepileptic drugs. It has some protective effect against all types of seizures.
  • Not toxic. Virtually no systemic or serious side effects.
  • One of the most popular benzodiazepines for anxiety.
  • Useful adjunct to SSRIs and SNRIs in the treatment of numerous anxiety disorders.
  • May have less abuse potential than some other benzodiazepines.
  • No significant clinical drug interactions have been reported.
  • Clonazepam can be quite effective in combination with SSRIs or SNRIs antidepressants18, 19 for treatment-resistant depression, protracted depression, and can accelerate the response to antidepressants.

Clonazepam Disadvantages

  • May cause respiratory depression, especially when taken with CNS depressants in overdose.
  • Scheduled IV status.
  • Sedative and behavioral side effects, including sedation, drowsiness, hypersalivation, lack of concentration and incoordination, ataxia, somnolence, depression.
  • Potentiates the effects of other sedatives including alcohol.
  • Potential for habituation, dependence, and abuse.

Mechanism of action

Clonazepam is a benzodiazepine that has anxiolytic, sedative, and anticonvulsant properties. It also has antitussive activity17.

Clonazepam exerts its anxiolytic and antiseizure effects by potentiating the inhibitory effects of gamma aminobutyric acid (GABA) on neuronal excitation via synaptic GABA-A receptor complexes.

Clonazepam has more selective anticonvulsant activity than most other benzodiazepines1.

Time to clear out of the system

The plasma half- life is approximately 30 to 40 hours.


Clonazepam, a high-potency long-acting benzodiazepine, was synthesized by Leo Sternbach. Clonazepam is a chlorinated derivative of nitrazepam. The drug was originally brought to market in 1975.

Further reading


  • 1. Brunton LL, Chabner BA, Knollman BC, editors. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12th Ed. McGraw-Hill, New York, p. 460
  • 2. Edinger JD, Fins AI, Sullivan RJ, Marsh GR, Dailey DS, Young M. Comparison of cognitive-behavioral therapy and clonazepam for treating periodic limb movement disorder. Sleep. 1996 Jun;19(5):442-4. PubMed
  • 3. Joy MS. Clonazepam: benzodiazepine therapy for the restless legs syndrome. ANNA J. 1997 Dec;24(6):686-9. PubMed
  • 4. Aurora RN, Zak RS, Maganti RK, et al. Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med. 2010 Feb 15;6(1):85-95. PubMed
  • 5. Reiter SR, Pollack MH, Rosenbaum JF, Cohen LS. Clonazepam for the treatment of social phobia. J Clin Psychiatry. 1990 Nov;51(11):470-2. PubMed
  • 6. Wang SM, Kim JB, Sakong JK, et al. The Efficacy and Safety of Clonazepam in Patients with Anxiety Disorder Taking Newer Antidepressants. Clin Psychopharmacol Neurosci. 2016 May 31;14(2):177-83. PubMed
  • 7. Sharma H. Treatment of Tardive Dyskinesia by tetrabenazine, clonazepam and vitamin E. Indian J Psychiatry. 2009 Apr;51(2):162-3. PubMed
  • 8. Pandurangi AA, Nayak RB, Bhogale GS, Patil NM, Chate SS, Chattopadhaya S. Clonazepam in the treatment of essential palatal tremors. Indian J Pharmacol. 2012 Jul-Aug;44(4):528-30. PubMed
  • 9. Jurisic Kvesic A, Zavoreo I, Basic Kes V, et al. The effectiveness of acupuncture versus clonazepam in patients with burning mouth syndrome. Acupunct Med. 2015 Aug;33(4):289-92. PubMed
  • 10. Shangguan Y, Liao H, Wang X. Clonazepam in the treatment of status epilepticus. Expert Rev Neurother. 2015;15(7):733-40. PubMed
  • 11. Márquez MF, Urias-Medina K, Gómez-Flores J, et al. Comparison of metoprolol vs clonazepam as a first treatment choice among patients with neurocardiogenic syncope. Gac Med Mex. 2008 Nov-Dec;144(6):503-7.
  • 12. Han SS, Nam EC, Won JY, Lee KU, Chun W, Choi HK, Levine RA. Clonazepam quiets tinnitus: a randomised crossover study with Ginkgo biloba. J Neurol Neurosurg Psychiatry. 2012 Aug;83(8):821-7 PubMed
  • 13. Londborg PD, Smith WT, Glaudin V, Painter JR. Short-term cotherapy with clonazepam and fluoxetine: anxiety, sleep disturbance and core symptoms of depression. J Affect Disord. 2000 Dec;61(1-2):73-9. PubMed
  • 14. Smith W, Londborg P, Glaudin V, Painter J. Is extended clonazepam cotherapy of fluoxetine effective for outpatients with major depression? J Affect Disord. 2002;70(3):251–259
  • 15. Mowla A, Ahmadzadeh L, Razeghian Jahromi L, Dastgheib SA. Comparing Gabapentin with Clonazepam for Residual Sleeping Problems following Antidepressant Therapy in Patients with Major Depressive Disorder: A Randomized Clinical Trial. Clin Drug Investig. 2015 Aug;35(8):513-7. PubMed
  • 16. Rosenberg HC, Tietz EI, Chiu TH. Tolerance to anticonvulsant effects in amygdala-kindled rats. Epilepsia. 1989 May-Jun;30(3):276-85. PubMed
  • 17. Wang SC, Chou DT, Wallenstein MC. Studies on the potency of various antitussive agents. Agents Actions. 1977 Sep;7(3):337-40.
  • 18. Morishita S. Clonazepam as a therapeutic adjunct to improve the management of depression. Hum Psychopharmacol. 2009 Apr;24(3):191-8. PubMed
  • 19. Dunlop BW, Davis PG. Combination treatment with benzodiazepines and SSRIs for comorbid anxiety and depression. Prim Care Companion J Clin Psychiatry. 2008;10(3):222-8. PubMed
  • 20. Amos K, Yeoh SC, Farah CS. Combined topical and systemic clonazepam therapy for the management of burning mouth syndrome: a retrospective pilot study. J Orofac Pain. 2011 Spring;25(2):125-30. PubMed

Published: December 02, 2016
Last updated: December 07, 2017

Interesting facts
Klonopin facts
  • The first benzo, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955.

More Facts
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