HOME WEB NEWS IMAGES CLASSIFIEDS YELLOW PAGESPOLLS - SURVEYS WIKI COUNTRIES PHOTOS US UK INDIA
Cities Stocks Weather Movies Coupons Travel Blogs Health Horoscope Maps ASIA EUROPE Classifieds Yellow Pages
 1
|
| |
| |
| Clonazepam | |
| Systematic (IUPAC) name | |
| 6-(2-chlorophenyl)-9-nitro-2,5-diazabicyclo[5.4.0]undeca-5,8,10,12-tetraen-3-one | |
| Identifiers | |
| CAS number | |
| ATC code | N03 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C15H10ClN3O3 |
| Mol. mass | 315.715 |
| Pharmacokinetic data | |
| Bioavailability | 90% |
| Metabolism | Hepatic CYP3A4 |
| Half life | 18–50 hours |
| Excretion | Renal |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status | |
| Routes | Oral, I.M., I.V, sublingual |
Clonazepam (marketed by Roche under the trade-names Klonopin in the United States and Rivotril or Rivatril in Europe, South America, Canada, India, and Australia) is a drug which is a benzodiazepine derivative. It is a highly potent anticonvulsant and anxiolytic.Cowen PJ; Green AR, Nutt DJ (Mar 1981). "Ethyl beta-carboline carboxylate lowers seizure threshold and antagonizes flurazepam-induced sedation in rats". Nature 290 (5801): 54-5. PMID 6259533. Clonazepam, also known as 5-(2-chlorphenyl)-1, 3-dihydro-7-nitro-2H-1, 4benzodiazepin-2-one, or as 6-(2-chlorophenyl)-9-nitro-2, 5-diazabicyclo[5.4.0]undeca-5, 8,10,12-tetraen-3-one (IUPAC name), is structurally related to nitrazepam.Pinder RM; Brogden RN, Speight TM, Avery GS (Nov 1976). "Clonazepam: a review of its pharmacological properties and therapeutic efficacy in epilepsy". Drugs 12 (5): 321-61. PMID 976134.
Contents |
Clonazepam is a chlorinated derivative of nitrazepam.Dreifuss FE; Penry JK, Rose SW, Kupferberg HJ, Dyken P, Sato S (Mar 1975). "Serum clonazepam concentrations in children with absence seizures". Neurology 25 (3): 255-8. PMID 1089913. Clonazepam is classed as a nitrobenzodiazepine along with nitrazepam and flunitrazepam.Robertson MD; Drummer OH (May 1995). "Postmortem drug metabolism by bacteria". J Forensic Sci 40 (3): 382-6. PMID 7782744. Aromatic nitro-containing compounds such as clonazepam produce superoxide free radicals during cellular metabolism by endothelial cells. The nitro anion radical produced during clonazepam metabolism rapidly reacts with oxygen to form the free radical superoxide.Rosen GM; Turner MJ 3rd (Feb 1988). "Synthesis of spin traps specific for hydroxyl radical". J Med Chem. 31 (2): 428-32. PMID 2828624. Rosen GM; Demos HA, Rauckman EJ (Aug 1984). "Not all aromatic nitro compounds form free radicals". Toxicol Lett. 22 (2): 145-52. PMID 6089382. Benzodiazepines, including clonazepam, bind to glial cell membranes with high affinity.Tardy M; Costa MF, Rolland B, Fages C, Gonnard P. (Apr 1981). "Benzodiazepine receptors on primary cultures of mouse astrocytes". J Neurochem 36 (4): 1587-9. PMID 6267195. Gallager DW; Mallorga P, Oertel W, Henneberry R, Tallman J (Feb 1981). "{3H}Diazepam binding in mammalian central nervous system: a pharmacological characterization". J Neurosci 1 (2): 218-25. PMID 6267221.
Clonazepam decreases levels of acetylcholinePetkov V; Georgiev VP, Getova D, Petkov VV (1982). "Effects of some benzodiazepines on the acetylcholine release in the anterior horn of the lateral cerebral ventricle of the cat". Acta Physiol Pharmacol Bulg 8 (3): 59-66. PMID 6133407. and decreases prolactin release.Grandison L (1982). "Suppression of prolactin secretion by benzodiazepines in vivo". Neuroendocrinology 34 (5): 369-73. PMID 6979001. Clonazepam is chemically related to quinazolines and is a hapten.Earley JV; Fryer RI, Ning RY (Jul 1979). "Quinazolines and 1,4-benzodiazepines. LXXXIX: Haptens useful in benzodiazepine immunoassay development". J Pharm Sci 68 (7): 845-50. PMID 458601. Clonazepam induces melanogenesis in melanoma cells via binding to high affinity sites and modulating cell differentiation.Matthew E; Laskin JD, Zimmerman EA, Weinstein IB, Hsu KC, Engelhardt DL (Jun 1981). "Benzodiazepines have high-affinity binding sites and induce melanogenesis in B16/C3 melanoma cells". Proc Natl Acad Sci U S A 78 (6): 3935-9. PMID 6267610.
One milligram of clonazepam is approximately equivalent to twenty milligrams of diazepam.Benzodiazepine Comparison Chart,B Jenson,2003 Because of its powerful anxiolytic properties, it is said to be among the class of "highly potent" benzodiazepines. Although benzodiazepines are valuable in the treatment of anxiety disorders, they carry a high potential for physical and psychological dependence with profound withdrawal symptoms, especially if discontinued abruptly or over rapidly in certain individuals. Caution is advised when taking this or any benzodiazepine medication longer than a few weeks.
Clonazepam appears to also have a secondary effect on the neurotransmitter serotonin.Lerner AG, Gelkopf M, Skladman I, Rudinski D, Nachshon H, Bleich A (2003). "Clonazepam treatment of lysergic acid diethylamide-induced hallucinogen persisting perception disorder with anxiety features". Int Clin Psychopharmacol 18 (2): 101–5. doi:10.1097/01.yic.0000053665.88477.46. PMID 12598822. It has shown itself to be highly effective as a short-term (3 weeks) adjunct to SSRI treatment in obsessive-compulsive disorder and clinical depression in reducing SSRI side effects with the combination being superior to SSRI treatment alone in a study funded by the manufacturers of clonazepam, Hoffman LaRoche Inc.Smith WT, Londborg PD, Glaudin V, Painter JR (1998). "Short-term augmentation of fluoxetine with clonazepam in the treatment of depression: a double-blind study". Am J Psychiatry 155 (10): 1339–45. PMID 9766764. Similar results have been found with some other anxiety disorders, but the role of the serotonergic effects enhancing the action of the SSRI treatment remains unclear in these cases due to clonazepam\'s primary anxiolytic mechanism of action.
Like other benzodiazepines, clonazepam acts on benzodiazepine receptors which enhance the binding of GABA to the GABAA receptor which results in inhibitory effects on the central nervous system.Skerritt JH; Johnston GA (6 May 1983). "Enhancement of GABA binding by benzodiazepines and related anxiolytics". Eur J Pharmacol 89 (3-4): 193-8. PMID 6135616. Benzodiazepines, however, do not have any effect on the levels of GABA in the brain.Varotto M; Roman G, Battistin L (30 Apr 1981). "[Pharmacological influences on the brain level and transport of GABA. I) Effect of various antipileptic drugs on brain levels of GABA]". Boll Soc Ital Biol Sper 57 (8): 904-8. PMID 7272065.
The anticonvulsant properties of clonazepam and other benzodiazepines may be in part or entirely due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors. Sustained repetitive firing seems to be limited by benzodiazepines effect of slowing recovery of sodium channels from inactivation.McLean MJ; Macdonald RL (Feb 1988). "Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture". J Pharmacol Exp Ther 244 (2): 789-95. PMID 2450203. Benzodiazepine drugs including clonazepam increase the inhibitory processes in the cerebral cortex.Zakusov VV; Ostrovskaya RU, Kozhechkin SN, Markovich VV, Molodavkin GM, Voronina TA (Oct 1977). "Further evidence for GABA-ergic mechanisms in the action of benzodiazepines" 229 (2): 313-26. PMID 23084.
Peak blood concentrations of 6.5–13.5 ng/mL were usually reached within 1–2 hours following a single 2 mg oral dose of micronized clonazepam in healthy adults. In some individuals, however, peak blood concentrations were reached at 4–8 hours.Monograph - Clonazepam -- Pharmacokinetics. Medscape (January 2006). Retrieved on 2007-12-30.
Clonazepam passes rapidly into the central nervous system with levels in the brain corresponding with levels of unbound clonazepam in the blood serum.Parry GJ (1976). "An animal model for the study of drugs in the central nervous system". Proc Aust Assoc Neurol 13: 83-8. PMID 1029011. Clonazepam plasma levels are very unreliable amongst patients. Plasma levels of clonazepam can vary as much as 10 fold between different patients.Gerna M; Morselli PL (21). "A simple and sensitive gas chromatographic method for the determination of clonazepam in human plasma". J Chromatogr 116 (2): 445-50. PMID 1245581.
Clonazepam is largely bound to plasma proteins.Tokola RA; Neuvonen PJ (1983). "Pharmacokinetics of antiepileptic drugs". Acta neurologica Scandinavica. Supplementum 97: 17-27. PMID 6143468. Clonazepam is broken down and metabolised to a benzophenone compound.Cano JP; Guintrand J, Aubert C, Viala A (Feb 1977). "Determination of flunitrazepam, desmethylflunitrazepam and clonazepam in plasma by gas liquid chromatography with an internal standard". Arzneimittelforschung 27 (2): 338-42. PMID 16619. The metabolites of clonazepam include 7-aminoclonazepam, 7-acetaminoclonazepam, 2-amino-2\'-chloro-5-nitrobenzophenone and 2,5-diamino-2\'-chlorobenzophenone and 3-hydroxy clonazepam.Ebel S; Schütz H (27). "[Studies on the detection of clonazepam and its main metabolites considering in particular thin-layer chromatography discrimination of nitrazepam and its major metabolic products (author\'s transl)]". Arzneimittelforschung 27 (2): 325-37. PMID 577149. Edelbroek PM; De Wolff FA (Oct 1978). "Improved micromethod for determination of underivatized clonazepam in serum by gas chromatography". Clinical chemistry 24 (10): 1774-7. PMID 699288.
Tolerance
In humans tolerance to the anticonvulsant effects of clonazepam occurs frequently.Loiseau P (1983). "[Benzodiazepines in the treatment of epilepsy]". Encephale 9 (4 Suppl 2): 287B-292B. PMID 6373234. Chronic use of benzodiazepines leads to the development of tolerance with a decrease of benzodiazepine binding sites. The degree of tolerance is more pronounced with clonazepam than with chlordiazepoxide.Crawley JN; Marangos PJ, Stivers J, Goodwin FK (Jan 1982). "Chronic clonazepam administration induces benzodiazepine receptor subsensitivity". Neuropharmacology 21 (1): 85-9. PMID 6278355. Short term therapy is generally more effective than long term therapy with clonazepam for the treatment of epilepsy.Bacia T; Purska-Rowińska E, Okuszko S (1980). "Clonazepam in the treatment of drug-resistant epilepsy: a clinical short and long term follow-up study". Monogr Neural Sci 5: 153-9. PMID 7033770. Many studies have found that tolerance develops to the anticonvulsant properties of clonazepam with chronic use, which limits its long term effectiveness as an anticonvulsant.Browne TR (May 1976). "Clonazepam. A review of a new anticonvulsant drug". Arch Neurol 33 (5): 326-32. PMID 817697.
Withdrawal
Sudden withdrawal from clonazepam may result in withdrawal symptoms including anxiety, irritability and potentially the life threatening condition status epilepticus. Antiepileptic drugs, benzodiazepines such as clonazepam in particular, should be reduced slowly and gradually when discontinuing the drug to reduce withdrawal effects.Bruni J (7 Apr 1979). "Recent advances in drug therapy for epilepsy". Can Med Assoc J 120 (7): 817-24. PMID 371777.
Abrupt or over-rapid withdrawal from clonazepam may result in the development of the benzodiazepine withdrawal syndrome with psychotic attacks characterised by dysphoric manifestations, irritability, aggressiveness, anxiety, and hallucinations.Sironi VA; Franzini A, Ravagnati L, Marossero F (Aug 1979). "Interictal acute psychoses in temporal lobe epilepsy during withdrawal of anticonvulsant therapy". J Neurol Neurosurg Psychiatry 42 (8): 724-30. PMID 490178.
Clonazepam is sometimes used for refractory epilepsies; however, long-term prophylactic treatment of epilepsy has considerable limitations, most notably the loss of antiepileptic effects due to tolerance, which renders the drug useless with long-term use, and also side effects such as sedation, which is why clonazepam and benzodiazepines as a class should generally only be prescribed for the acute management of epilepsies.Isojärvi, JI; Tokola RA (Dec 1998). "Benzodiazepines in the treatment of epilepsy in people with intellectual disability". J Intellect Disabil Res 42 (1): 80-92. PMID 10030438. Clonazepam is less effective and potent as an anticonvulsant in bringing infantile seizures under control compared with nitrazepam in the treatment of West syndrome, which is an age-dependent epilepsy affecting the very young. However, as with other epilepies treated with benzodiazepines, long-term therapy becomes ineffective with prolonged therapy, and the side effects of hypotonia and drowsiness are troublesome with clonazepam therapy; other antiepileptic agents are therefore recommended for long-term therapy, possibly Corticotropin (ACTH) or vigabatrin. Clonazepam is therefore not recommended for widespread use in the management of seizures related to West syndrome.Djurić, M; Marjanović B, Zamurović D (May-Jun 2001). "[West syndrome--new therapeutic approach]". Srp Arh Celok Lek 129 (1): 72-7. PMID 15637997. Also with long-term use, abrupt or overrapid withdrawal from clonazepam can precipitate withdrawal-related seizures if tolerance and physical dependence have developed.
Clonazepam has been used in the management of seizure disorders in children and also for infantile spasms. However, usefulness of clonazepam is limited due to its deleterious effect on neurological function, especially its negative effect on cognition. Clobazam, a 1,5-benzodiazepine, has shown to be less neurotoxic than 1,4-benzodiazepines such as clonazepam.Farrell K (1986). "Benzodiazepines in the treatment of children with epilepsy". Epilepsia 1: 45-5. PMID 3743524. Munn R; Farrell K (Nov-Dec 1993). "Open study of clobazam in refractory epilepsy". Pediatr Neurol 9 (6): 465-9. PMID 7605555.
Clonazepam may be prescribed for:
In the treatment of acute epilepsy via intravenous administration approximately 72.5 per cent of patients show improved EEG patterns, 17.5 per cent show no improvement and for 10 per cent of patients clonazepam has a paradoxical effect and worsens EEG readings.Perlwitz R; Grimmberger E, Schmidtsdorf R (Jun 1980). "[Immediate effect of intravenous clonazepam on the EEG]". Psychiatr Neurol Med Psychol (Leipz) 32 (6): 338-44. PMID 7403357.
Clonazepam is rarely used as a treatment for insomnia. It has not been marketed for the treatment of insomnia mainly because its long half life makes it unsuitable for this application.
Clonazepam was approved in the United States as a generic drug in 1997 and is now manufactured and marketed by several companies.
Clonazepam is available in the U.S. as tablets (0.5, 1.0, and 2 mg) and orally disintegrating tablets (wafers) (0.125, 0.25, 0.5, 1.0, and 2 mg). In other countries, clonazepam is usually available as tablets (0.5 and 2 mg), orally disintegrating tablets (0.25, 0.5, 1 and 2 mg) oral solution (drops, 2.5 mg/mL), as well as solution for injection or intravenous infusion, containing 1 mg clonazepam per ampoule (e.g. Rivotril® inj.).
Like all benzodiazepines, clonazepam is a benzodiazepine receptor agonist. Long-term use (more than 2–4 weeks) can lead to a number of problems, including muscle weakness and fatigue, tolerance, physical dependence and withdrawal syndromes upon discontinuation. The benzodiazepine withdrawal syndrome, which may appear during reduction or withdrawal of clonazepam treatment, can be reduced in intensity with gradual reduction of dosage.
Many individuals treated on a long-term basis develop a form of dependence known as "low-dose dependence", as was shown in one double-blind, placebo-controlled study of 34 therapeutic low-dose benzodiazepine users—physiological dependence was demonstrated via flumazenil-precipitated withdrawal.Bernik MA; Gorenstein C, Vieira Filho AH (1998). "Stressful reactions and panic attacks induced by flumazenil in chronic benzodiazepine users". Journal of psychopharmacology (Oxford, England) 12 (2): 146-50. PMID 9694026.
Use of alcohol or other CNS depressants while taking clonazepam greatly intensifies the effects (and side effects) of the drug. Side effects of the drug itself are generally benign, but sudden withdrawal after long-term use can cause severe, even fatal, symptoms.
Caution in the Elderly. Increased risk of impairments, falls and drug accumulation.[citation needed]
Caution in children. Clonazepam is not recommended for use in those under 18. Use in very young children may be especially hazardous. Clonazepam was implicated along with the drugs diphenylhydantoin and nitrazepam in the death of a 7 and a half month old girl. She developed inclusions consisting of lamellar profiles, situated in membrane-bound cytosomes which were found mainly in astrocytes, but also in neurones and in axons of peripheral nerves before dying. Lipofuscin bodies were also found to be increased in number.Figols J; Cervós-Navarro J, Wolman M (Jan 1986). "Encephalopathy with astrocytic residual bodies. Report of a case and review of the literature". Histol Histopathol 1 (1): 59-67. PMID 2980102.
Caution using high dosages of clonazepam. Doses higher than 0.5 - 1 mg per day is associated with significant sedation.Hollister LE (1975). "Dose-ranging studies of clonazepam in man". Psychopharmacol Commun 1 (1): 89-92. PMID 1223993.
Clonazepam may aggravate hepatic porphyria.Bonkowsky HL; Sinclair PR, Emery S, Sinclair JF (Jun 1980). "Seizure management in acute hepatic porphyria: risks of valproate and clonazepam". Neurology 30 (6): 588-92. PMID 6770287. Reynolds NC Jr; Miska RM (Apr 1981). "Safety of anticonvulsants in hepatic porphyrias". Neurology 31 (4): 480-4. PMID 7194443.
Caution in schizophrenia. Clonazepam has been found to be not effective in the management of schizophrenia and has been found to increase the risk of violent behavior.Karson CN; Weinberger DR, Bigelow L, Wyatt RJ (Dec 1982). "Clonazepam treatment of chronic schizophrenia: negative results in a double-blind, placebo-controlled trial". Am J Psychiatry 139 (12): 1627-8. PMID 6756174.
Clonazepam decreases the levels of carbamazepine,Lander CM; Eadie MJ, Tyrer JH (1975). "Interactions between anticonvulsants". Proc Aust Assoc Neurol 12: 111-6. PMID 2912. and likewise be reduced in its levels by carbamazepine.Lai AA, Levy RH; Cutler RE (Sep 1978). "Time-course of interaction between carbamazepine and clonazepam in normal man". Clinical pharmacology and therapeutics 24 (3): 316-23. PMID 688725. Clonazepam may affect levels of phenytoin (diphenylhydantoin) by decreasing, or increasing.Windorfer A Jr; Sauer W (1977). "Drug interactions during anticonvulsant therapy in childhood: diphenylhydantoin, primidone, phenobarbitone, clonazepam, nitrazepam, carbamazepin and dipropylacetate". Neuropadiatrie 8: 29-41. PMID 321985. Windorfer A; Weinmann HM, Stünkel S (Mar 1977). "[Laboratory controls in long-term treatment with anticonvulsive drugs (author\'s transl)]". Monatsschr Kinderheilkd 125 (3): 122-8. PMID 323695. In turn Phenytoin may lower clonazepam plasma levels, by increasing the speed of clonazepam clearance by approximately 50% and decreasing its half life by 31 per cent.Khoo KC; Mendels J, Rothbart M, Garland WA, Colburn WA, Min BH, Lucek R, Carbone JJ, Boxenbaum HG, Kaplan SA (Sep 1980). "Influence of phenytoin and phenobarbital on the disposition of a single oral dose of clonazepam". Clin Pharmacol Ther 28 (3): 368-75. PMID 7408397. Clonazepam increases the levels of primidone,Windorfer A Jr; Sauer W (1977). "Drug interactions during anticonvulsant therapy in childhood: diphenylhydantoin, primidone, phenobarbitone, clonazepam, nitrazepam, carbamazepin and dipropylacetate". Neuropadiatrie 8: 29-41. PMID 321985. and phenobarbital.Bendarzewska-Nawrocka B; Pietruszewska E, Stepień L, Bidziński J, Bacia T (Jan-Feb 1980). "[Relationship between blood serum luminal and diphenylhydantoin level and the results of treatment and other clinical data in drug-resistant epilepsy]". Neurol Neurochir Pol 14 (1): 39-45. PMID 7374896. Cannabidiol a drug with anticonvulsant properties, reduces the anticonvulsant protency of clonazepam.Consroe P; Wolkin A (Apr 1977). "Cannabidiol--antiepileptic drug comparisons and interactions in experimentally induced seizures in rats". J Pharmacol Exp Ther 201 (1): 26-32. PMID 850145.
Benzodiazepines including clonazepam may inhibit the glucuronidation of morphine leading to increased levels of and prolongation of the effects of morphine. Clonazepam may inhibit morphine metabolism more than any other benzodiazepine.Pacifici GM; Gustafsson LL, Säwe J, Rane A (Apr 1986). "Metabolic interaction between morphine and various benzodiazepines". Acta Pharmacol Toxicol (Copenh) 58 (4): 249-52. PMID 2872767.
Clonazepam, like many other benzodiazepines, may impair one\'s ability to drive or operate heavy machinery. The central nervous system depressing effects of the drug can be augmented by alcohol consumption. Benzodiazepines have been shown to cause both psychological and physical dependence. Patients physically dependent on clonazepam should be slowly titrated off under the supervision of a qualified healthcare professional to avoid withdrawal or rebound symptoms.
10–15% of individuals treated with clonazepam on a long-term basis (in excess of 30 days of continuous use) develop a protracted withdrawal syndrome. Protracted withdrawal lasts for months, years, or a lifetime after clonazepam is discontinued. Protracted withdrawal results from structural brain damage, which is often irreversible.Ashton C (March 1995). "Protracted Withdrawal from Benzodiazepines: The Post-Withdrawal Syndrome". Psychiatric Annals, U.K 25 (3): 174-179. Common protracted withdrawal symptoms include:Protracted Withdrawal from Benzodiazepines: The Post-Withdrawal Syndrome,C Ashton,1995
However, in 1993 the New England Journal of Medicine reported there is no reliable evidence to support the existence of a persistent benzodiazepine withdrawal syndrome, and this alleged syndrome has been described only in anecdotal reports, with patients typically reporting "withdrawal" symptoms not present during or before benzodiazepine treatment that persist for many months or years after treatment is stopped. Experimental neuropharmacologic studies document that all the side effects of benzodiazepines, whether behavioral or neurochemical, disappear within several days or weeks after the drug is eliminated. The weight of evidence indicates that any new symptoms that persist for more than two months after the last dose of a benzodiazepine either are part of the premorbid condition or have appeared by coincidence or as a consequence of the natural history of the underlying illness. Shader RI, Greenblatt DJ (1993). "Use of benzodiazepines in anxiety disorders". N. Engl. J. Med. 328 (19): 1398–405. PMID 8292115.
There is some medical evidence of various malformations e.g. cardiac or facial deformations when used in early pregnancy, however the data is not conclusive. The data is also inconclusive whether benzodiazepines such as clonazepam cause developmental deficits or decreases in IQ when taken during pregnancy. Clonazepam when used late in pregnancy may result in the development of a severe benzodiazepine withdrawal syndrome in the neonate and also floppy infant syndrome. Withdrawal symptoms from benzodiazepines in the neonate may include hypotonia, and reluctance to suck, to apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. These symptoms may persist for hours or months after birth.McElhatton PR (Nov-Dec 1994). "The effects of benzodiazepine use during pregnancy and lactation". Reprod Toxicol 8 (6): 461-75. PMID 7881198.
An individual who has consumed too much clonazepam will display one or more of the following symptoms:
Coma may be cyclic with the individual alternating from a comatose state to a hyperalert state of consciousness, as occurred in a 4-year-old boy who suffered an overdose of clonazepam.Welch TR; Rumack BH, Hammond K (1977). "Clonazepam overdose resulting in cyclic coma". Clin Toxicol 10 (4): 433-6. PMID 862377.
Unless combined with other drugs, deep coma or other manifestations of severe central nervous system depression are rare, and the mortality rate associated with poisoning is very low. As with other benzodiazepines, overdose symptoms of clonazepam may be reversed with flumazenil (Romazicon). In epileptic patients medicated with benzodiazepines, including clonazepam, flumazenil should not be given, however, even in a benzodiazepine overdose, since it may precipitate status epilepticus. Instead, intubation, controlled or supported ventilation and circulatory support within intensive care is indicated in epileptics overdosed by benzodiazepines. Flumazenil should only be considered as a last resort and administered very slowly, fractionally, after an evaluation by a neurologist, specialised in epilepsy, possibly under continuous EEG-monitoring in order to record possible early signs of a seizure.
Relatively few cases of addiction arise from legitimate use of benzodiazepines.O\'brien CP (2005). "Benzodiazepine use, abuse, and dependence". J Clin Psychiatry 66 Suppl 2: 28–33. PMID 15762817. Despite its classification as a high-potency benzodiazepine, clonazepam is not commonly encountered on the black market. Its unique pharmacological profile seems to provide effective anxiolysis without inducing a significant euphoria, unlike the much more commonly abused alprazolam.
When clonazepam is obtained by drug users, it is commonly used as a secondary drug to increase the pleasure resulting from a primary drug, or to lessen or prevent some of the primary drug\'s negative side effects.[citation needed] It is important to note, however, that addiction and physical dependence are distinct conditions.
This article is licensed under the GNU Free Documentation License. It uses material from Wikipedia
