Citalopram

Source: Wikipedia, the free encyclopedia.
This article is about the
racemic form of the drug. For its (S)-enantiomer, see Escitalopram
.

Citalopram
(R)-(−)-citalopram (top),
(S)-(+)-citalopram (bottom)
Clinical data
Pronunciation/saɪˈtæləˌpræm, sɪ-/;[1]
Trade namesCelexa, Cipramil, others[2]
AHFS/Drugs.comMonograph
MedlinePlusa699001
License data
Pregnancy
category
Dependence
liability		Low
Addiction
liability		Low
Routes of
administration		oral, intravenous[4][5][6]
Drug classSelective serotonin reuptake inhibitor (SSRI)[7]
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability80%
peak at 4 hours[7]
Protein binding<80%[10]
MetabolismLiver (CYP3A4 and CYP2C19)
MetabolitesDesmethylcitalopram (DCT) and didesmethylcitalopram (DDCT)
Elimination half-life35 hours
ExcretionMostly as unmetabolized citalopram, partly DCT, and traces of DDCT in urine
Identifiers
  • (RS)-1-[3-(Dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile
JSmol)
ChiralityRacemic mixture
SMILES
  • Fc1ccc(cc1)C3(OCc2cc(C#N)ccc23)CCCN(C)C
  • InChI=1S/C20H21FN2O/c1-23(2)11-3-10-20(17-5-7-18(21)8-6-17)19-9-4-15(13-22)12-16(19)14-24-20/h4-9,12H,3,10-11,14H2,1-2H3 checkY
  • Key:WSEQXVZVJXJVFP-UHFFFAOYSA-N checkY
  (verify)

Citalopram, sold under the brand name Celexa among others, is an

intravenously (injected into a vein) to initiate treatment, before switching to the oral route of administration for continuation of treatment.[4] It has also been used intravenously in other parts of the world in some other circumstances.[5][6]

Common side effects include nausea, trouble sleeping, sexual problems, shakiness, feeling tired, and sweating.

MAO inhibitor.[7] There are concerns that use during pregnancy may harm the fetus.[3]

Citalopram was approved for medical use in the United States in 1998.

generic medication.[12] In 2022, it was the 40th most commonly prescribed medication in the United States, with more than 15 million prescriptions.[13][14]

Medical uses

United States one-cent coin
(size 19.05 mm/0.75 in)

Depression

In the United States, citalopram is approved to treat

National Institute for Health and Clinical Excellence ranking of ten antidepressants for efficacy and cost-effectiveness, citalopram is fifth in effectiveness (after mirtazapine, escitalopram, venlafaxine, and sertraline) and fourth in cost-effectiveness.[18]

Evidence for the effectiveness of citalopram for treating depression in children is uncertain.[19][20]

Panic disorder

Citalopram is licensed in the UK[21] and other European countries[22] for panic disorder, with or without agoraphobia.

Other

Citalopram may be used off-label to treat anxiety, and dysthymia,[23] premenstrual dysphoric disorder, body dysmorphic disorder, and obsessive–compulsive disorder.[24]

It appears to be as effective as fluvoxamine and paroxetine in obsessive–compulsive disorder.[25] Some data suggest the effectiveness of intravenous infusion of citalopram in resistant OCD.[5] Citalopram is well tolerated and as effective as moclobemide in social anxiety disorder.[26] There are studies suggesting that citalopram can be useful in reducing aggressive and impulsive behavior.[27][28] It appears to be superior to placebo for behavioural disturbances associated with dementia.[29] It has also been used successfully for hypersexuality in early Alzheimer's disease.[30]

A meta-analysis, including studies with fluoxetine, paroxetine, sertraline, escitalopram, and citalopram versus placebo, showed SSRIs to be effective in reducing symptoms of premenstrual syndrome, whether taken continuously or just in the luteal phase.[31] For alcoholism, citalopram has produced a modest reduction alcohol intake and increase in drink-free days in studies of alcoholics, possibly by decreasing desire or reducing the reward.[32]

While on its own citalopram is less effective than

refractory cases, combination therapy may be more effective.[33]

Citalopram and other SSRIs can be used to treat

hot flashes.[34]
: 107 

A 2009 multisite randomized controlled study found no benefit and some adverse effects in autistic children from citalopram, raising doubts about whether SSRIs are effective for treating repetitive behavior in children with autism.[35]

Some research suggests 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 effects.[36]

Administration

Citalopram is typically taken in one dose, either in the morning or evening. It can be taken with or without food. Its absorption does not increase when taken with food,[37][10] but doing so can help prevent nausea. Nausea is often caused when the 5-HT3 receptors actively absorb free serotonin, as this receptor is present within the digestive tract.[38]

Adverse effects

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 associated with increased serotonin. Citalopram is also a mild antihistamine, which may be responsible for some of its sedating properties.[34]: 104 

Other common side effects of citalopram include

hallucinations, severe allergic reactions and photosensitivity.[37] If sedation occurs, the dose may be taken at bedtime rather than in the morning. Some data suggest citalopram may cause nightmares.[39] Citalopram is associated with a higher risk of arrhythmia than other SSRIs.[40][41]

Citalopram and other SSRIs can induce a

mixed state, especially in those with undiagnosed bipolar disorder.[34]
: 105  According to an article published in 2020, one of the other rare side effects of Citalopram could be triggering visual snow syndrome; which does not resolve after the discontinuation of the medicine.[42]

Sexual dysfunction

Sexual dysfunction is often a side effect of SSRIs.[43] Some people experience persistent sexual side effects when taking SSRIs or after discontinuing them.[44] Symptoms of medication-induced sexual dysfunction from antidepressants include difficulty with orgasm, erection, or ejaculation.[44] Other symptoms may be genital anesthesia, anhedonia, decreased libido, vaginal lubrication issues, and nipple insensitivity in women. Rates are unknown, and there is no established treatment.[45]

Abnormal heart rhythm

In August 2011, the FDA announced, "Citalopram causes dose-dependent QT interval prolongation. Citalopram should no longer be prescribed at doses greater than 40 mg per day".[46] A further clarification, issued in March 2012, restricted the maximum dose to 20 mg for subgroups of patients, including those older than 60 years and those taking an inhibitor of cytochrome P450 2C19.7.[47]

Endocrine effects

As with other SSRIs, citalopram can cause an increase in serum prolactin level.[48] Citalopram has no significant effect on insulin sensitivity in women of reproductive age[49] and no changes in glycaemic control were seen in another trial.[50]

Exposure in pregnancy

Antidepressant exposure (including citalopram) during pregnancy is associated with shorter duration of gestation (by three days), increased risk of preterm delivery (by 55%), lower birth weight (by 75 g), and lower Apgar scores (by <0.4 points). Antidepressant exposure is not associated with an increased risk of spontaneous abortion.[51] It is uncertain whether there is an increased prevalence of septal heart defects among children whose mothers were prescribed an SSRI in early pregnancy.[52][53]

Overdose

Overdosage may result in vomiting, sedation, disturbances in heart rhythm, dizziness, sweating, nausea, tremors, and rarely amnesia, confusion, coma, or convulsions.[34]: 105  Overdose deaths have occurred, sometimes involving other drugs, but also with citalopram as the sole agent. Citalopram and N-desmethylcitalopram may be quantified 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.[46][54][55] It is the most dangerous of SSRIs in overdose.[56]

Suicidality

In the United States, citalopram carries a boxed warning stating it may increase suicidal thinking and behavior in those under age 24.[37]

Discontinuation syndrome

paraesthesiae, sleeping problems (difficulty sleeping and intense dreams), feeling dizzy, agitated or anxious, nausea, vomiting, tremors, confusion, sweating, headache, diarrhea, palpitations, changes in emotions, irritability, and eye or eyesight problems. Treatment with citalopram should be reduced gradually when treatment is finished.[59]

Interactions

Serotonin syndrome

Citalopram should not be taken with

neurotoxic effects. However, these concerns are still disputed as the exact pharmacodynamic effects of citalopram and MDMA have yet to be fully identified.[citation needed] Citalopram is contraindicated in individuals taking MAOIs, owing to a potential for serotonin syndrome
.

Other interactions

SSRIs, including citalopram, can increase the risk of bleeding, especially when coupled with

anticoagulants.[37] Taking citalopram with omeprazole may cause higher blood levels of citalopram. This is a potentially dangerous interaction, so dosage adjustments may be needed or alternatives may be prescribed.[63][64][10]

Pharmacokinetics

Citalopram is considered safe and well tolerated in the

therapeutic dose range. Distinct from some other agents in its class, it exhibits linear pharmacokinetics and minimal drug interaction potential, making it a better choice for the elderly or comorbid patients.[65]

Stereochemistry

Citalopram has one stereocenter, to which a 4-fluoro phenyl group and an N, N-dimethyl-3-aminopropyl group bind. As a result of 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

lipophilic
compounds water-soluble.

Metabolism

Citalopram is metabolized in the liver mostly by CYP2C19, but also by CYP3A4 and CYP2D6. Metabolites desmethylcitalopram and didesmethylcitalopram are significantly less energetic and their contribution to the overall action of citalopram is negligible. The half-life of citalopram is about 35 hours. Approximately 80% is cleared by the liver and 20% by the kidneys.[67] The elimination process is slower in the elderly and in patients with liver or kidney failure. With once-daily dosing, steady plasma concentrations are achieved in about a week. Potent inhibitors of CYP2C19 and 3A4 might decrease citalopram clearance.[10] Tobacco smoke exposure was found to inhibit the biotransformation of citalopram in animals, suggesting that the elimination rate of citalopram is decreased after tobacco smoke exposure. After intragastric administration, the half-life of the

racemic mixture of citalopram was increased by about 287%.[68]

Metabolism of citalopram in humans.[69][70][71]
Binding profile[72]
Receptor Ki (nM)
SERT 1.6
NET 6190
5-HT2C 617
α1

1211

M1 1430
H1 283

History

Citalopram was first synthesized in 1972 by chemist Klaus Bøgesø[73] and his research group at the pharmaceutical company Lundbeck and was first marketed in 1989 in Denmark. It was first marketed in the US in 1998.[74] The original patent expired in 2003, allowing other companies to legally produce and market generic versions.

Society and culture

Brand names

Citalopram is sold under these brand names:

  • Akarin (Denmark, Nycomed)
  • C Pram S (India)
  • Celapram (Australia,[75] New Zealand),
  • Celexa (U.S. and Canada, Forest Laboratories, Inc.)
  • Celica (Australia)[75]
  • Ciazil (Australia,[75] New Zealand)
  • Cilate (South Africa)
  • Cilift (South Africa)
  • Cimal (South America, by Roemmers and Recalcine)
  • Cipralex (Europe, South Africa)
  • Cipram (Denmark, Turkey, H. Lundbeck A/S)
  • Cipramil (Australia,[75] Brazil, Belgium, Chile, Finland, Germany, Netherlands, Iceland, Ireland, Israel, New Zealand, Norway, Russia, South Africa, Sweden, United Kingdom)
  • Cipraned, Cinapen (Greece)
  • Ciprapine (Ireland)
  • Ciprotan (Ireland)
  • Citabax, Citaxin (Poland)
  • Cital (Poland)
  • Citalec (Czech Republic, Slovakia)
  • Citalex (Iran, Serbia)
  • Citalo (Australia,[75] Egypt, Pakistan)
  • Citalopram (Canada, Denmark, Finland, Germany, Ireland, The Netherlands, New Zealand, Spain, Sweden, Switzerland, United Kingdom, U.S.)
  • Citol (Russia, Turkey)
  • Citox (Mexico)
  • Citrol (Europe and Australia)[75]
  • Citta (Brazil)
  • Dalsan (Eastern Europe)
  • Denyl (Brazil)
  • Depram (Egypt)[76][77]
  • Elopram (Italy)
  • Estar (Pakistan)
  • Humorup (Argentina)
  • Humorap (Peru, Bolivia)
  • Lopraxer (Greece)[78]
  • Oropram (Iceland, Actavis),
  • Opra (Russia)
  • Pram (Russia)
  • Pramcit (Pakistan)
  • Procimax (Brazil)
  • Recital (Israel, Thrima Inc. for Unipharm Ltd.)
  • Sepram (Finland)
  • Seropram (various European countries, including the Czech Republic)
  • Szetalo (India)
  • Talam (Europe and Australia)[75]
  • Temperax (Argentina, Chile, Peru)
  • Vodelax (Turkey)
  • Zentius (South America, by Roemmers and Recalcine)
  • Zetalo (India)
  • Cipratal (Kuwait, GCC)
  • Zylotex (Portugal)[2]


European Commission fine

On 19 June 2013, the

antitrust law.[79]

Other uses

Citalopram is also a

Schistosomula have high mortality when treated with citalopram.[80]

See also

References

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