Citalopram (brand name: Celexa , Cipramil and others) is an antidepressant drug of selective serotonin reuptake inhibitor class (SSRI). It has the approval of the US Food and Drug Administration to treat severe depression, which it received in 1998, and is prescribed for other conditions. In Australia, Britain, Germany, Portugal, Poland, and most European countries, it is licensed for episodes of depression and panic disorder with or without agoraphobia. In Spain and Denmark it is also used for obsessive-compulsive disorder.
Video Citalopram
Medical use
Depression
At the National Institute for Health and Clinical Excellence, the ranking of 10 antidepressants for the effectiveness and cost-effectiveness of citalopram is the fifth effectiveness (after mirtazapine, escitalopram, venlafaxine, and sertraline) and fourth in cost-effectiveness. The ranking results are based on a meta-analysis by Andrea Cipriani. In another analysis by Cipriani, citalopram was found to be more efficacious than paroxetine and reboxetine, and more acceptable than tricyclics, reboxetine, and venlafaxine, but less efficacious than escitalopram.
Evidence of the effectiveness of citalopram for treating depression in children is uncertain.
Panic disorder
Citalopram is licensed in the UK and other European countries for panic disorder, with or without agoraphobia. The dose is 10 mg/day for a week, increasing to 20-30 mg/day, with a maximum of 40 mg/day.
Off-label
Citalopram is often used off-label to treat anxiety, panic disorder, dysthymia, premenstrual dysphoric disorder, body dysmorphic disorder, and obsessive-compulsive disorder.
It has been shown to be effective in 85% of patients with generalized anxiety disorder, including some who fail with other SSRIs. It is also just as effective as fluvoxamine and paroxetine in obsessive-compulsive disorder. Some data show the effectiveness of intravenous citalopram infusions in resistant OCD. Citalopram is well tolerated and as effective as moclobemide in social anxiety disorders. There is research showing that citalopram can be useful in reducing aggressive and impulsive behavior. It appears to be superior to placebo for behavioral disorders associated with dementia. It has also been used successfully for hypersexuality in early Alzheimer's disease.
A meta-analysis, including studies with fluoxetine, paroxetine, sertraline, escitalopram, and citalopram versus placebo, showed SSRIs were effective in reducing the symptoms of premenstrual syndrome, whether taken continuously or only in the luteal phase. Citalopram has resulted in a modest reduction in intake of alcoholic beverages and an increase in drink-free days in alcohol studies, possibly by reducing the desire or reducing the reward.
Citalopram has been found to reduce the symptoms of diabetic neuropathy.
While citalopram alone is less effective than amitriptyline in migraine prevention, in refractory cases, combination therapy may be more effective.
Citalopram and other SSRIs can be used to treat hot flashes.
A randomized, controlled multisite study of 2009 found no benefit and some adverse effects on autistic children from citalopram, raising doubts as to whether SSRIs are effective for treating repetitive behavior in children with autism.
Several studies have shown that citalopram interacts with the binding of cannabinoid proteins in the brains of rats, and this is suggested as a potential cause of some of the antidepressant effects of the drug.
Administration
Citalopram is usually 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, but doing so can help prevent nausea. Nausea is often caused when 5HT3 active receptors absorb free serotonin, because these receptors are present in the gastrointestinal tract. 5HT3 receptors stimulate vomiting. These side effects, if present, will subside as the body adjusts to the medication.
Citalopram is considered safe and well tolerated in the therapeutic dose range. Unlike some other agents in its class, it shows linear pharmacokinetics and minimal drug interaction potential, making it a better choice for elderly or comorbid patients.
Maps Citalopram
Adverse effects
Sexual dysfunction is often a side effect with SSRIs. In particular, common side effects include difficulty getting aroused, lack of interest in sex, and anorgasmia (difficulty reaching orgasm). However, one study showed, when remission of major depressive disorder was achieved, the quality of life and sexual satisfaction were reported to be higher despite sexual side effects.
Citalopram theoretically causes side effects by increasing serotonin concentrations in other parts of the body (eg, intestines). Other side effects, such as apathy elevation and emotional flattening, may be caused by a decrease in dopamine release associated with increased serotonin. Citalopram is also a mild antihistamine, which may be responsible for some of its tranquilizing properties.
Common side effects of citalopram include drowsiness, insomnia, nausea, weight changes (usually weight), increased appetite, clear dreams, frequent urination, decreased sex drive, anorgasmia, dry mouth, increased sweating, tremor, diarrhea , excessive yawning, heavy tinnitus, and fatigue. Less common side effects include bruxism, vomiting, cardiac arrhythmia, changes in blood pressure, dilated pupils, anxiety, mood swings, headaches, and dizziness. Rare side effects include seizures, hallucinations, severe allergic reactions and photosensitivity. If sedation occurs, the dose may be taken at bedtime rather than in the morning. Some data suggest that citalopram can cause nightmares.
Withdrawal symptoms may occur when the drug suddenly stops, such as paresthesias, sleep problems (sleeplessness and intense dreams), dizziness, anxiety or anxiety, nausea, vomiting, tremors, confusion, sweating, headaches, diarrhea, palpitations, emotional changes, irritation, and eye or vision problems. Treatment with citalopram should be gradually reduced when treatment is complete.
Citalopram and other SSRIs can induce a mixed state, especially in those with undiagnosed bipolar disorder.
Sexual Dysfunction Post SSRI
Some people experience persistent sexual side effects after they stop using SSRIs. This is known as Post-SSRI Sexual Dysfunction (PSSD). Common symptoms in this case include genital anesthesia, erectile dysfunction, anhedonia, decreased libido, premature ejaculation, vaginal lubrication problems, and female nipple discomfort. The prevalence of PSSD is unknown, and no treatment is established.
Abnormal heart rhythms
In August 2011, the FDA announced, "Citalopram leads to the extension of the dose-dependent QT interval.Citalopram should no longer be prescribed at doses greater than 40 mg per day". Further clarification issued in March 2012 limits the maximum dose to 20 mg for a subgroup of patients, including those over 60 years and those who use cytochrome P450 2C19.7 inhibitors.
Endocrine effect
As with other SSRIs, citalopram may cause elevated serum prolactin levels. Citalopram had no significant effect on insulin sensitivity in women of reproductive age and no change in glycemic control was seen in other trials.
Exposure in pregnancy
Exposure to antidepressants (including citalopram) during pregnancy is associated with shorter duration of pregnancy (by three days), an increased risk of preterm delivery (55%), low birth weight (75 g), and lower Apgar score (by & lt; 0.4 points). Exposure to antidepressants is not associated with an increased risk of spontaneous abortion. It is uncertain whether there is an increased prevalence of septal defects in children whose mothers are prescribed SSRIs early in pregnancy.
Interactions
Citalopram should not be taken with St. John's wort, tryptophan or 5-HTP as the resulting drug interactions can cause serotonin syndrome. With St. John's Wort, this may be caused by compounds in plant extracts reducing the efficacy of cytochrome P450 liver enzymes that process citalopram. It has also been suggested that such compounds, including hypericin, hyperforin and flavonoids, can have SSRI-mimetic effects on the nervous system, although this is debatable. One study found that Hypericum extract had the same effect in treating moderate depression as citalopram, with fewer side effects.
Tryptophan and 5-HTP are precursors to serotonin and may cause increased serotonin. When taken with SSRIs, such as citalopram, this can cause a lethal serotonin level. This may also occur when SSRIs are taken with CFS (serotonin release agents) as in the case of MDMA. It is possible that SSRIs may reduce the associated effect due to CFS, since SSRIs stop Serotonin reuptake by blocking the SERT. This will allow less serotonin in and out of the transporter, thereby reducing the likelihood of neurotoxic effects. However, these concerns are debatable because the precise pharmacodynamic effects of citalopram and MDMA have not been fully identified.
SSRIs, including citalopram, can increase the risk of bleeding, especially when combined with aspirin, NSAIDs, warfarin, or other anticoagulants. Citalopram is contraindicated in individuals who use MAOI, because of the potential for serotonin syndrome.
Taking citalopram with omeprazole can lead to higher levels of blood citalopram. This is a potentially harmful interaction, so dose adjustments may be required or alternatives may be prescribed.
SSRI termination syndrome has been reported when treatment is stopped. These include sensory, gastrointestinal symptoms, dizziness, lethargy, and sleep disorders, as well as psychological symptoms such as anxiety/agitation, irritability, and poor concentration. Sensations such as electric shock are typical for SSRI termination. Tapered citalopram therapy, as opposed to sudden termination, is recommended to reduce the incidence and severity of symptoms of cessation. Some doctors choose to divert patients to Prozac (fluoxetine) when stopping citalopram because fluoxetine has a longer half-life (ie remains in the body longer than citalopram). This can avoid many of the severe withdrawal symptoms associated with citalopram termination. This can be done by administering a single dose of 20 mg of fluoxetine or by starting with a low dose of fluoxetine and slowly decreasing. One of these recipes can be written in liquid form to allow for a very slow and gradual dose reduction. Alternatively, a patient who wishes to stop taking citalopram can visit a compounding pharmacy where recipes can be rearranged into smaller doses.
Overdose
Overdose can cause vomiting, sedation, heart rhythm disturbances, dizziness, sweating, nausea, tremor, and rarely amnesia, confusion, coma, or seizures. Overdose death has occurred, sometimes involving other drugs, but also with citalopram as a single agent. Citalopram and N-desmethylcitalopram can be quantified in blood or plasma to confirm the diagnosis of poisoning in hospitalized patients or to assist in investigation of medicolegal death. Blood or plasma citalopram concentrations are usually in the range of 50-400 g/l in people receiving therapeutic drugs, 1000-3000 g/l in patients who survive an acute overdose and 3-30 mg/l in those who do not persist. This is the most dangerous of SSRIs in an overdose.
Suicidality
In the United States, citalopram carries a box warning that states can improve suicidal thinking and behavior in those under the age of 24.
Stereochemistry
Citalopram has one stereocenter, where the 4-fluoro phenyl group and the Nd-N-nimin-3-aminopropyl group bond bind N, N . As a result of this chirality, molecules exist in (two) enantiomer forms (mirror images). They are called S - () - citalopram and R - (-) - citalopram.
Citalopram is sold as a racemic mixture, comprising 50% ( R ) - (-) - citalopram and 50% ( S ) - () - citalopram. Only ( S ) - () enantiomer has the desired antidepressant effect. Lundbeck is now marketing ( S ) - () enantiomer, its generic name is escitalopram. While citalopram is given as hydrobromide, escitalopram is sold as oxalate salt (hydrooxalate). In both cases, the salt form of the amine makes this lipophilic compound soluble in water.
Metabolism
Citalopram is metabolized in the liver mostly by CYP2C19, but also by CYP3A4 and CYP2D6. Desmethylcitalopram and desmethylcitalopram metabolites are significantly less energetic and their contribution to overall citalopram action is negligible. The half-life of citalopram is about 35 hours. About 80% is cleansed by the liver and 20% by the kidneys. The elimination process is slower in the elderly and in patients with liver or kidney failure. With a once daily dose, a stable plasma concentration is achieved in about a week. Potential inhibitors of CYP2C19 and 3A4 may decrease citalopram clearance. Exposure to tobacco smoke was found to inhibit biotransformation of citalopram in animals, suggesting that the rate of citalopram elimination decreased after exposure to tobacco smoke. After intragastric administration, the half-life of the citalopram racemic mixture increased by approximately 287%.
Pharmacology
History
Citalopram was first synthesized in 1972 by scientists at the Lundbeck pharmaceutical company and was first marketed in 1989 in Denmark. It was first marketed in the US in 1998. The patent expired in 2003, allowing other companies to legally produce generic versions. Lundbeck has released escitalopram and obtained a new patent for it. In the United States, Forest Labs manufactures and markets drugs.
Brand name
Citalopram is sold under the following brand names:
The European Commission is fine
On June 19, 2013, the European Commission imposed a fine of EUR93.8 million on Danish pharmaceutical company Lundbeck, plus a total of EUR52.2 million in some generic pharmaceutical manufacturers. This in response to Lundbeck entering into an agreement with the company to postpone the sale of their generic citalopram after Lundbeck's patent on the drug has ended, thereby reducing competition in violation of European antitrust laws.
See also
- Mepyramine
- Pheniramine
- Escitalopram
References
External links
- Celexa product page on Forest Laboratories website
- Cipramil Patient Information Sheet
- US. National Library of Medicine: Drug Information Portal - Citalopram
- Citalopram in PubMed Health
Source of the article : Wikipedia
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