Citalopram

Citalopram
Systematic (IUPAC) name
(RS)-1-[3-(dimethylamino)propyl]-1-
(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a699001
Pregnancy cat. C(US)
Legal status Prescription only
Routes Oral
Pharmacokinetic data
Bioavailability 80%
peak at 4 hours[1]
Metabolism hepatic (CYP3A4 & CYP2C19)
Half-life 35 hours
Excretion Mostly as unmetabolized citalopram, partly DCT and traces of DDCT in urine
Identifiers
CAS number 59729-33-8 YesY
ATC code N06AB04 N06AB10
PubChem CID 2771
DrugBank DB00215
ChemSpider 2669 YesY
UNII 0DHU5B8D6V YesY
KEGG D07704 YesY
ChEBI CHEBI:3723 YesY
ChEMBL CHEMBL549 YesY
Chemical data
Formula C20H21FN2O 
Mol. mass 324.392 g/mol
SMILES eMolecules & PubChem
 YesY(what is this?)  (verify)

Citalopram (play /sˈtælɵpræm/;[2] brand names: Celexa, Cipramil) is an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) class. It has U.S. Food and Drug Administration (FDA) approval to treat major depression, and is prescribed off-label for a number of anxiety conditions.

Contents

Medical uses

Citalopram HBr tablets in 20 mg (coral, marked 508) and 40 mg (white, marked 509), and a coin(size 19.05mm/0.75").

Citalopram is approved to treat the symptoms of major depression.[3]

Off-label

Citalopram is frequently used off-label to treat anxiety, panic disorder, PMDD, Body dysmorphic disorder and OCD.[4]

Citalopram has been found to greatly reduce the symptoms of diabetic neuropathy[5] and premature ejaculation.[6] There is also evidence that citalopram may be effective in the treatment of post-stroke pathological crying.[7]

While on its own citalopram is less effective than amitriptyline in the prevention of migraines, in refractory cases combination therapy may be more effective.[8]

Citalopram and other SSRIs can be used to treat hot flashes.[9]

A 2009 multisite randomized controlled study found no benefit and some adverse effects in autistic children from citalopram, raising doubts whether SSRIs are effective for treating repetitive behavior in children with autism.[10]

Some research suggests that citalopram interacts with cannabinoid protein-couplings in the rat brain, and this is put forward as a potential cause of some of the drug's antidepressant effect.[11]

Administration

Citalopram is typically taken in one dose, either in the morning or evening. Citalopram can be taken with or without food. The absorption of citalopram does not increase when taken with food,[12] but can help prevent against nausea. Nausea is often caused when the 5HT3 receptors actively absorbs free serotonin, as this receptor is present within the digestive tract.[13] The 5HT3 receptors stimulate vomiting. This side effect, if present, should subside as the body adjusts to the medication.

Citalopram is considered safe and well-tolerated in the therapeutic dose range. Distinct from some other agents in its class, citalopram exhibits linear pharmacokinetics and minimal drug interaction potential, making it a better choice for the elderly or comorbid patients.[14]

Adverse effects

Sexual dysfunction is often a side effect with SSRIs. Specifically, common side effects include difficulty becoming aroused, lack of interest in sex, and anorgasmia (trouble achieving orgasm). Genital anesthesia,[15] loss of or decreased response to sexual stimuli, and ejaculatory anhedonia are also possible. Although usually reversible, these sexual side effects can last for months or years after the drug has been completely withdrawn.[16] This is known as Post SSRI Sexual Dysfunction.

Citalopram theoretically causes side effects by increasing the concentration of serotonin in other parts of the body (e.g., the intestines). Other side effects, such as increased apathy and emotional flattening, may be caused by the decrease in dopamine release that is associated with increased serotonin. Citalopram is also a mild antihistamine, which may be responsible for some of its sedating properties.[17]

Common side effects of citalopram include drowsiness, insomnia, nausea, weight changes, frequent urination, decreased sex drive, anorgasmia, dry mouth,[18] increased sweating, trembling, diarrhea, excessive yawning, and fatigue. Less common side effects include bruxism, vomiting, cardiac arrhythmia, blood pressure changes, dilated pupils, anxiety, mood swings, headache, and dizziness. Rare side effects include convulsions, hallucinations, and severe allergic reactions.[3] If sedation occurs, the dose may be taken at bedtime rather than in the morning.

Citalopram and other SSRIs can induce a mixed state, especially in those with undiagnosed bipolar disorder.[19]

Citalopram should not be taken with St John's wort, tryptophan or 5-HTP as the resulting drug interaction could lead to serotonin syndrome.[20] With St John's wort, this may be caused by compounds in the plant extract reducing the efficacy of the hepatic cytochrome P450 enzymes that process citalopram.[21] It has also been suggested that such compounds, including hypericin, hyperforin and flavonoids, could have SSRI-mimetic effects on the nervous system, although this is still subject to debate.[22] One study found that Hypericum extracts had similar effects in treating moderate depression as citalopram, with fewer side effects.[23] Tryptophan and 5-HTP are precursors to serotonin and can cause a rise in serotonin. When taken with an SSRI, such as citalopram, this can lead to levels of serotonin that can be lethal.

In the US, Federal health regulators are warning doctors not to prescribe high doses of the antidepressant Citalopram, because of the risk of fatal heart complications. The Food and Drug Administration said the drug could interfere with the heart’s electrical activity at doses above 40 milligrams and lead to sudden death.

Citalopram is contraindicated in individuals taking MAOIs, due to potential for serotonin syndrome.

SSRIs, including citalopram, can increase the risk of bleeding, especially when coupled with aspirin, NSAIDs, warfarin, or other anticoagulants.[24]

When taken with Prilosec, the clearance of citalopram may be reduced, leading to higher blood levels of citalopram. Prilosec inhibits the CYP450 2C19 enzyme, one of the two primary enzymes responsible for the metabolism of citalopram. Dosage adjustments may be needed due to this effect.[citation needed]

SSRI discontinuation syndrome has been reported when treatment is stopped. Tapering off citalopram therapy, as opposed to abrupt discontinuation, is recommended in order to diminish the occurrence and severity of discontinuation symptoms. Some doctors may choose to switch a patient to Prozac (Fluoxetine) when discontinuing Citalopram as Prozac has a much longer half-life (i.e. stays in the body longer compared to Citalopram). This may avoid many of the severe withdrawal symptoms associated with Citalopram discontinuation. This can be done either by administering a single 20 mg dose of Prozac or by beginning on a low dosage of Prozac and slowly tapering down. Either of these prescriptions may be written in liquid form to allow a very slow and gradual tapering down in dosage. Alternatively, a patient wishing to stop taking Citalopram may visit a compounding pharmacy where his or her prescription may be re-arranged into progressively smaller dosages.

According to the FDA, Celexa "can cause abnormal changes to the electrical activity of the heart." and can lead to fatal changes in the heart's rhythm. The higher the dose, the greater the risk to the heart.[25]

Suicidality

In the United States, citalopram, like other antidepressants, carries a black box warning stating that it may increase suicidal thinking and behavior in those under age 24.[26]

Overdosage

Overdosage may result in vomiting, sedation, disturbances in heart rhythm, dizziness, sweating, nausea, tremor, and rarely amnesia, confusion, coma, or convulsions.[19] A number of overdose deaths have occurred, sometimes involving other drugs but also with citalopram as the sole agent. Citalopram and N-desmethylcitalopram may be quantitated in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients or to assist in a medicolegal death investigation. Blood or plasma citalopram concentrations are usually in a range of 50-400 μg/L in persons receiving the drug therapeutically, 1000-3000 μg/L in patients who survive acute overdosage and 3–30 mg/L in those who do not survive.[27][28][29] </ref> ref name="emaxhealth">[1], The Food and drug administration states that doses higher than 40 milligrams have been linked to Long QT Syndrome (LQTS) a heart rhythm disorder that can potentially cause fast, chaotic heartbeats that could trigger a sudden fainting spell or seizure. In some cases, the heart beats so erratically for so long that it can cause sudden death.'</ref>

Stereochemistry

Citalopram has one stereocenter, to which a 4-fluorophenyl group and an N,N-dimethyl-3-aminopropyl group bind. Due to this chirality, the molecule exists in (two) enantiomeric forms (mirror images). They are termed S-(+)-citalopram and R-(–)-citalopram.

S-(+)-citalopram R-(–)-citalopram
S-(+)-citalopram R-(–)-citalopram
(S)-(+)-citalopram (R)-(–)-citalopram

Citalopram is sold as a racemic mixture, consisting of 50% (R)-(−)-citalopram and 50% (S)-(+)-citalopram. Only the (S)-(+) enantiomer has the desired antidepressant effect. Lundbeck now markets the (S)-(+) enantiomer, the generic name of which is escitalopram. Whereas citalopram is supplied as the hydrobromide, escitalopram is sold as the oxalate salt (hydrooxalate).[30] In both cases, the salt forms of the amine make these otherwise lipophilic compounds water-soluble.

Metabolites

Citalopram metabolites desmethylcitalopram and didesmethylcitalopram are significantly less energetic and their contribution to the overall action of citalopram is negligible.

History

Citalopram was originally created in 1989[31] by the pharmaceutical company Lundbeck. The patent expired in 2003, allowing other companies to legally produce generic versions. Lundbeck has recently released an updated formulation called escitalopram,[citation needed] which is the S-enantiomer of the racemic citalopram (see b), and acquired a new patent for it. In the United States, Forest Labs manufactures and markets the drug.

Brand names

Citalopram is sold under the brand-names Celexa (U.S. and Canada, Forest Laboratories, Inc.), Citalopram (USA, United Kingdom, Denmark), Citta (Brazil), Cipramil (Australia, Brazil, Finland, Germany, Netherlands, Ireland, Israel, Norway, Sweden, United Kingdom, New Zealand, South Africa, Russia), Elopram (Italy)[32], Citol (Russia), Vodelax (Turkey), Citrol, Seropram, Talam (Europe and Australia), Citabax, Citaxin (Poland), Citalec (Slovakia, Czech Republic), Recital (Israel, Thrima Inc. for Unipharm Ltd.), Zetalo (India), Celapram, Ciazil (Australia, New Zealand), Zentius, Cimal (South America, by Roemmers and Recalcine), Ciprapine (Ireland), Cilift (South Africa), Citox (Mexico), Temperax (Chile, Peru, Argentina), Talohexal (Australia), Citopam (Australia), Akarin (Denmark, Nycomed), Cipram (Turkey, Denmark, H. Lundbeck A/S), Dalsan (Eastern Europe), Pram (Russia), Pramcit (Pakistan), Celius (Greece), Humorup (Argentina), Oropram (Iceland, Actavis), Opra (Russia), and Zylotex (Portugal).

References

  1. ^ http://www.psychiatrictimes.com/medications/citalopram-hydrobromide-tablet
  2. ^ "citalopram". Merriam-Webster, Incorporated. http://medical.merriam-webster.com/medical/citalopram. Retrieved 2008-10-13. 
  3. ^ a b Cerner Multum Inc. Rxlist.com. 2009. http://www.rxlist.com/celexa-drug.htm
  4. ^ Poore, Jerod. Celexa. Crazy Meds. 2010. http://crazymeds.us/celexa.html
  5. ^ Sindrup SH, Bjerre U, Dejgaard A, Brøsen K, Aaes-Jørgensen T, Gram LF (1992). "The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy". Clin. Pharmacol. Ther. 52 (5): 547–52. doi:10.1038/clpt.1992.183. PMID 1424428. 
  6. ^ Atmaca M, Kuloglu M, Tezcan E, Semercioz A (2002). "The efficacy of citalopram in the treatment of premature ejaculation (prem-e): a placebo-controlled study". Int. J. Impot. Res. 14 (6): 502–5. doi:10.1038/sj.ijir.3900918. PMID 12494286. 
  7. ^ Andersen G, Vestergaard K, Riis JO (1993). "Citalopram for post-stroke pathological crying". Lancet 342 (8875): 837–9. doi:10.1016/0140-6736(93)92696-Q. PMID 8104273. 
  8. ^ Rampello L, Alvano A, Chiechio S, et al. (2004). "Evaluation of the prophylactic efficacy of amitriptyline and citalopram, alone or in combination, in patients with comorbidity of depression, migraine, and tension-type headache". Neuropsychobiology 50 (4): 322–8. doi:10.1159/000080960. PMID 15539864. 
  9. ^ Stahl, S. Stahl's Essential Psychopharmacology: The Prescriber's Guide. Cambridge University Press: New York, NY. 2009. pp. 87.
  10. ^ King BH, Hollander E, Sikich L et al. (2009). "Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism". Arch Gen Psychiatry 66 (6): 583–90. doi:10.1001/archgenpsychiatry.2009.30. PMID 19487623. Lay summary – Los Angeles Times (2009-06-02). 
  11. ^ Effects of chronic treatment with citalopram on cannabinoid and opioid receptor-mediated G-protein coupling in discrete rat brain regions. Shirley A. Hesketh, Adrian K. Brennan, David S. Jessop and David P. Finn. Springer Berlin / Heidelberg. Volume 198, Number 1 / May, 2008. ISSN: 0033-3158 (Print) 1432-2072 (Online) http://www.springerlink.com/content/2127100x043n3674/
  12. ^ http://www.drugs.com/celexa.html
  13. ^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. p. 187. ISBN 0-443-07145-4
  14. ^ Keller MB (2000). "Citalopram therapy for depression: a review of 10 years of European experience and data from U.S. clinical trials". The Journal of clinical psychiatry 61 (12): 896–908. doi:10.4088/JCP.v61n1202. PMID 11206593. http://www.biopsychiatry.com/citalopram.html. 
  15. ^ Bolton JM, Sareen J, Reiss JP (2006). "Genital anaesthesia persisting six years after sertraline discontinuation". J Sex Marital Ther 32 (4): 327–30. doi:10.1080/00926230600666410. PMID 16709553. http://www.informaworld.com/openurl?genre=article&doi=10.1080/00926230600666410&magic=pubmed. 
  16. ^ Csoka AB, Bahrick AS, Mehtonen O-P (2008). "Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors (SSRIs)". J Sex Med. 5 (1): 227–33. doi:10.1111/j.1743-6109.2007.00630.x. PMID 18173768. http://www.blackwell-synergy.com/doi/abs/10.1111/j.1743-6109.2007.00630.x. 
  17. ^ Stahl, S. Stahl's Essential Psychopharmacology: The Prescriber's Guide. Cambridge University Press: New York, NY. 2009. pp. 84.
  18. ^ Cerner Multum Inc. Drugs.com. 2009. http://www.drugs.com/celexa.html
  19. ^ a b Stahl, S. Stahl's Essential Psychopharmacology: The Prescriber's Guide. Cambridge University Press: New York, NY. 2009. pp. 85.
  20. ^ Karch, Amy (2006). 2006 Lippincott's Nursing Drug Guide. Philadelphia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo: Lippincott Williams & Wilkins. ISBN 1-58255-436-6. 
  21. ^ http://www.medsafe.govt.nz/Profs/PUarticles/sjw.htm accessed Feb 27 2009
  22. ^ http://www.umm.edu/altmed/articles/st-johns-000276.htm accessed Feb 27 2009
  23. ^ M. Gastpar, et al. (2006). "Comparative Efficacy and Safety of a Once-Daily Dosage of Hypericum Extract STW3-VI and Citalopram in Patients with Moderate Depression: A Double-Blind, Randomised, Multicentre, Placebo-Controlled Study". Pharmacopsychiatry 39 (2): 66–75. doi:10.1055/s-2006-931544. PMID 16555167. http://www.thieme-connect.com/ejournals/abstract/pharmaco/doi/10.1055/s-2006-931544. Retrieved Feb 27 2009. 
  24. ^ Citalopram PI Sheet. 2009. http://www.frx.com/pi/Citalopram_pi.pdf
  25. ^ http://www.webmd.com/heart-disease/news/20110824/fda-warns-of-celexa-heart-risk?ecd=wnl_nal_emw_082411
  26. ^ Citalopraim PI Sheet. 2009. http://www.frx.com/pi/Citalopram_pi.pdf
  27. ^ Personne M, Sjöberg G, Persson H. Citalopram overdose--review of cases treated in Swedish hospitals. J. Tox. Clin. Tox. 35: 237-240, 1997.
  28. ^ Luchini D, Morabito G, Centini F. Case report of a fatal intoxication by citalopram. Am. J. For. Med. Pathol. 26: 352-354, 2005.
  29. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 319-322.
  30. ^ Celexa.com
  31. ^ Dorell K, Cohen MA, Huprikar SS, Gorman JM, Jones M (2005). "Citalopram-induced diplopia". Psychosomatics 46 (1): 91–3. doi:10.1176/appi.psy.46.1.91. PMID 15765832. 
  32. ^ http://www.drugs.com/international/elopram.html

External links


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Look at other dictionaries:

  • Citalopram — Énantiomère R du citalopram (en haut) et S citalopram (en bas) Général Nom IUPAC …   Wikipédia en Français

  • Citalopram — Nombre (IUPAC) sistemático (RS) 1 [3 (dimetilamino)propil] 1 (4 fluorofenil) 1,3 dihidroisobenzofurano 5 carbonitrilo Identificadores …   Wikipedia Español

  • Citalopram — Strukturformel (R) Isomer (oben) und (S) Isomer (unten) 1:1 Gemisch der Stereoisomeren …   Deutsch Wikipedia

  • citalopram — ci·tal·o·pram (sī tălʹō prăm ) n. A drug of the SSRI class that is used primarily to treat depression.   [citalo (from rearrangement of (ph)t(h)al(ene)c(arbon)i(trile), one of its constituents) + pram, antidepressant suff. (propyl + amine).] * *… …   Universalium

  • citalopram — noun A selective serotonin reuptake inhibitor used to treat depression, anxiety, and body dysmorphic disorder …   Wiktionary

  • citalopram — ci·tal·o·pram sī tal ə .pram, si n an antidepressant drug that is administered orally in the form of its hydrobromide C20H21FN2O·HBr and functions as an SSRI see celexa * * * n. an antidepressant drug that acts by prolonging the action of the… …   Medical dictionary

  • citalopram — n. an antidepressant drug that acts by prolonging the action of the neurotransmitter serotonin (5 hydroxytryptamine) in the brain (see SSRI). It is taken by mouth for the treatment of depression and panic disorder; side effects may include… …   The new mediacal dictionary

  • citalopram — A drug used to treat depression. It belongs to the families of drugs called antidepressant agents and selective serotonin reuptake inhibitors (SSRIs). Also called Celexa …   English dictionary of cancer terms

  • citalopram hydrobromide — ci·tal·o·pram hy·dro·bro·mide (si talґo pram) [USP] a selective serotonin reuptake inhibitor (SSRI), chemically unrelated to other SSRI s and consisting of a racemic mixture of two stereoisomers (S and R , the S isomer being pharmaceutically… …   Medical dictionary

  • 59729-33-8 — Citalopram citalopram Général Nom IUPAC (RS) 1 [3 (dimethylamino)propyl] 1 (4 fluorophenyl) 1,3 dihydro[3,4]benzofuran 5 carbonitrile …   Wikipédia en Français


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