| Systematic (IUPAC) name | |
|---|---|
| (RS)-1-[3-(dimethylamino)propyl]-1- (4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile |
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| 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 |
| ATC code | N06AB04 N06AB10 |
| PubChem | CID 2771 |
| DrugBank | DB00215 |
| ChemSpider | 2669 |
| UNII | 0DHU5B8D6V |
| KEGG | D07704 |
| ChEBI | CHEBI:3723 |
| ChEMBL | CHEMBL549 |
| Chemical data | |
| Formula | C20H21FN2O |
| Mol. mass | 324.392 g/mol |
| SMILES | eMolecules & PubChem |
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Citalopram ( /saɪˈtælɵpræm/;[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 |
Citalopram is approved to treat the symptoms of major depression.[3]
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]
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]
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.
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]
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 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][30]
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).[31] In both cases, the salt forms of the amine make these otherwise lipophilic compounds water-soluble.
Citalopram metabolites desmethylcitalopram and didesmethylcitalopram are significantly less energetic and their contribution to the overall action of citalopram is negligible.
Citalopram was originally created in 1989[32] 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, 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.
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,Belgium, Finland, Germany, Netherlands, Ireland, Israel, Norway, Sweden, United Kingdom, New Zealand, South Africa, Russia), Elopram (Italy)[33], 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).
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