Citalopram - Wikipedia, the free encyclopedia http://en.wikipedia.

org/wiki/Citalopram

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Citalopram - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Citalopram

Citalopram (trade name: Celexa, Cipramil) is an

Citalopram
antidepressant drug of the selective serotonin reuptake
inhibitor (SSRI) class. It has FDA approval to treat major
depression, and is prescribed off-label for a number of
anxiety conditions.

1 History Systematic (IUPAC) name

2 Indications
(RS)-1-[3-(dimethylamino)propyl]-1-
2.1 Approved
2.2 Unapproved, off-label and investigational (4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile
2.3 Availability Identifiers
3 Dosage and administration CAS number 59729-33-8
4 Side effects and drug interactions
ATC code N06AB04 N06AB10
4.1 Suicidality
4.2 Overdosage PubChem CID 2771

5 Stereochemistry DrugBank DB00215

6 Metabolites ChemSpider 2669
7 Genetic factors related to antidepressant efficacy Chemical data
8 References
9 External links Formula C20H21FN2O
Mol. mass 324.392 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 80%
Citalopram (pronounced /saɪˈtælɵpræm/)[1] was originally
hepatic (CYP3A4 & CYP2C19)
created in 1989[2] by the pharmaceutical company Metabolism
Lundbeck. The patent expired in 2003, allowing other Half-life 35 hours
companies to legally produce generic versions. Lundbeck has Excretion Mostly as unmetabolized citalopram,
recently released an updated formulation called escitalopram partly DCT and traces of DDCT in
(also known as Cipralex or Lexapro),[citation needed] which urine
is the S-enantiomer of the racemic citalopram (see b), and
Therapeutic considerations
acquired a new patent for it. In the United States, Forest Labs
manufactures and markets the drug. Pregnancy C(US)
cat.
Legal status ℞ Prescription only
Routes Oral
Approved (what is this?) (verify) (http://en.wikipedia.org
/w/index.php?&diff=cur&oldid=322138290)
Citalopram is approved to treat the symptoms of major
depression.[3]

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Unapproved, off-label and investigational

Citalopram is frequently used off-label to treat anxiety, panic disorder,

ADHD, PMDD, Body dysmorphic disorder and OCD.[4]

Citalopram HBr tablets in 20 mg Citalopram has been found to greatly reduce the symptoms of diabetic
(coral, marked 508) and 40 mg neuropathy[5] and premature ejaculation.[6] There is also evidence that
(white, marked 509), and a US citalopram may be effective in the treatment of post-stroke pathological
Penny. 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]

Availability

Citalopram is sold under the brand-names Celexa (U.S. and Canada, Forest Laboratories, Inc.), Cipramil
(Australia, Brazil, Finland, Germany, Netherlands, Ireland, Norway, Sweden, United Kingdom, New Zealand,
South Africa), Elopram (Italy)[12] Citol, 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), Pramcit (Pakistan), and Celius (Greece), Humorup
(Argentina), Oropram (Iceland, Actavis).

Citalopram is available in 10 mg, 20 mg, and 40 mg tablets, as well as 10 mg/5 mL peppermint flavor oral
solution. The recommended starting dose is 20 mg/day, with a target dose of 40 mg/day. Increased efficacy has
not been proven beyond 40 mg/day, but some prescribers may increase the dose to 60 mg/day or more. The
recommendation is that dose increases do not exceed 20 mg/day increases per week.

Citalopram is generally considered safe and well-tolerated in the therapeutic dose range of 10 to 60 mg/day (a
dose of 60 mg/day is reserved for patients who do not respond to lower doses). A doctor must always monitor a
patient taking an SSRI such as citalopram. 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.[13]

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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.[14]

Common side effects of citalopram include drowsiness, insomnia, nausea, weight changes, frequent urination,
decreased sex drive, anorgasmia, dry mouth,[15] increased sweating, trembling, diarrhea, excessive yawning, and
fatigue. Less common side effects include bruxism, vomiting, cardiac arrhythmia, blood pressure changes,
anxiety, mood swings, headache, and dizziness. Rare side effects include convulsions, hallucinations, and severe
allergic reactions[16]. 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.[17]

Citalopram should not be taken with St John's wort, as the resulting drug interaction could lead to serotonin
syndrome.[18] This may be caused by compounds in the plant extract reducing the efficacy of the hepatic
cytochrome P450 enzymes that process citalopram.[19] 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.[20] One study found that Hypericum extracts had similar effects in
treating moderate depression as citalopram, with fewer side effects.[21]

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.[22]

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.

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.

Suicidality

Citalopram, like other antidepressants, carries a black box warning stating that it may increase suicidal thinking
and behavior in those under age 24. Beyond age 24 there is no increased risk for suicidality.[23]

Overdosage

Acute overdosage, usually intentional, has been observed in a number of instances but the outcome is generally
favorable. Overdosage may result in vomiting, sedation, disturbances in heart rhythm, dizziness, sweating,

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nausea, tremor, and rarely amnesia, confusion, coma, or convulsions.[24] 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.[25][26][27]

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

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).[28] In both cases, the salt forms of the amine makes these otherwise
lipophilic compounds water-soluble.

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

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Citalopram is a P-glycoprotein (Pgp) substrate and is actively transported by that protein from the brain. The
efficacy of citalopram in people possessing a certain version of Pgp (genetic TT-allele) is likely to be diminished.
This suggests that in non-responders to citalopram a switch to an antidepressant which is not a Pgp substrate,
such as fluoxetine (Prozac, Fontex) or mirtazapine (Remeron)—but not to venlafaxine (Effexor), amitriptyline
(Elavil) or paroxetine (Paxil), which are Pgp substrates—may be beneficial.[29]
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29. ^ Uhr M, Tontsch A, Namendorf C, Ripke S, Lucae
S, Ising M, Dose T, Ebinger M, Rosenhagen M, Kohli
M, Kloiber S, Salyakina D, Bettecken T, Specht M,
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Celexa product page on Forest Laboratories web site (http://www.frx.com/products/celexa.aspx)

Cipramil Patient Information Leaflet (http://emc.medicines.org.uk/emc/assets/c/html
/displaydoc.asp?documentid=1070) Cipramil Patient Information Leaflet
U.S. National Library of Medicine: Drug Information Portal - Citalopram (http://druginfo.nlm.nih.gov
/drugportal/dpdirect.jsp?name=Citalopram)
Citalopram Survival Guide (http://www.nomorepanic.co.uk/showthread.php?t=46980) Extensive
information about citalopram use and potential side effects. Updated regularly.
Retrieved from "http://en.wikipedia.org/wiki/Citalopram"
Categories: Selective serotonin reuptake inhibitors | Nitriles | Organofluorides | Isobenzofurans | Amines

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