Citalopram (citalopram hydrobromide)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Citalopram hydrobromide, a selective serotonin-reuptake inhibitor (SSRI), is an antidepressant.
The mechanism of action of citalopram is unclear, but is thought to be related to its potentiation of serotonergic effects in the CNS resulting from the inhibition of CNS neuronal uptake of serotonin (5-hydroxytryptamine (5-HT)). As a selective serotonin-reuptake inhibitor (SSRI), citalopram has minimal effects on norepinephrine and dopamine reuptake. Citalopram has no or very low affinity for serotonergic receptor subtypes (5-HT1A and 5-HT2A receptors), dopamine D1 and D2, alpha1- or alpha2-adrenergic, beta-adrenergic, histaminergic (H1), GABA, muscarinic cholinergic, or benzodiazepine receptors.
Citalopram is a racemic (50:50) mixture of the R- and S-enantiomers. The inhibition of serotonin (5-HT) reuptake is primarily due to the S-enantiomer.
Following a single 40-mg oral dose of citalopram as a tablet, the manufacturer states that peak plasma concentrations occur at about 4 hours. Following a single 30-mg oral dose of citalopram as a capsule, peak plasma concentrations occur at about 3.5 hours. The absolute bioavailability of citalopram is approximately 80% relative to an IV dose.
Food does not substantially affect the absorption of citalopram. The single- and multiple-dose pharmacokinetics of citalopram are linear and dose-proportional in a dosage range of 10-40 mg daily. With once-daily dosing, steady-state plasma concentrations are achieved within approximately 1 week.
At steady state, the extent of accumulation of citalopram in plasma, based on the half-life, is expected to be about 2.5 times higher than the plasma concentrations observed after a single dose of the drug. The binding of citalopram, demethylcitalopram, and didemethylcitalopram to human plasma proteins in vitro is about 80%. Citalopram is distributed into breastmilk in humans.
Citalopram is metabolized to demethylcitalopram, didemethylcitalopram, citalopram-N-oxide, and a deaminated propionic acid derivative. In vitro studies have indicated that cytochrome P-450 (CYP) 3A4 and 2C19 isoenzymes are the principal enzymes involved in the N-demethylation of citalopram to demethylcitalopram. Genetic variations in CYP2C19 can influence the metabolism of citalopram (see Pharmacogenomic Considerations under Dosage and Administration).
In humans, unchanged citalopram is the predominant compound in plasma. At steady state, the concentrations of demethylcitalopram and didemethylcitalopram in plasma are approximately one-half and one-tenth, respectively, that of the parent drug. In vitro studies have demonstrated that citalopram is at least 8 times more potent than its metabolites in the inhibition of serotonin reuptake.
Thus, citalopram's metabolites are unlikely to contribute to the antidepressant and other clinical actions of the drug. The elimination half-life of citalopram averages approximately 35 hours in adults with normal renal and hepatic function.
In healthy individuals >=60 years of age, the AUC and half-life of citalopram were increased by an average of approximately 30% and 50%, respectively, in a single-dose study and by an average of approximately 23% and 30%, respectively, in a multiple-dose study. The effect of gender on the pharmacokinetics of citalopram has not been fully elucidated to date. The manufacturer states that in 3 pharmacokinetic studies, the AUC of citalopram in women was 1.5-2 times higher than that found in men; however, this difference was not observed in 5 other pharmacokinetic studies performed with the drug.
In clinical studies, no differences in steady-state plasma citalopram concentrations were observed between men and women. In addition, there were no gender differences in the pharmacokinetics of the principal metabolites of citalopram, demethylcitalopram and didemethylcitalopram. Therefore, the manufacturer states that no adjustment of citalopram dosage on the basis of gender is necessary.
Oral citalopram clearance is reduced by 17% in patients with mild to moderate renal impairment. No dosage adjustment of citalopram is warranted in these patients. The effect of severe renal impairment on the pharmacokinetics of citalopram has not been fully evaluated to date.
Oral citalopram clearance is reduced by 37% and the elimination half-life is doubled in patients with hepatic impairment. The maximum recommended dosage of citalopram should be reduced in hepatic impairment.
USES: This medication is used to treat depression. Citalopram belongs to a class of drugs known as selective serotonin reuptake inhibitors (SSRIs). It works by helping to restore the balance of a certain natural substance (serotonin) in the brain.
Generic name: citalopram hydrobromide
Pronunciation: (sye-TAL-oh-pram)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Citalopram
Indications
The following indications are listed for Citalopram:
- Major Depressive Disorder
Also known as: Major Unipolar Illness, Unipolar Mood Disorder.
Dosing
Dosage of citalopram hydrobromide is expressed in terms of citalopram.
The manufacturers state that at least 2 weeks must elapse between discontinuance of a monoamine oxidase (MAO) inhibitor and initiation of citalopram therapy and that at least 2 weeks must elapse between discontinuance of citalopram and initiation of MAO inhibitor therapy.
Because withdrawal effects may occur with discontinuance of citalopram or other selective serotonin-reuptake inhibitors (SSRIs), abrupt discontinuance of these drugs should be avoided whenever possible. When citalopram therapy is discontinued, the dosage should be reduced gradually whenever possible.
Citalopram hydrobromide is administered orally.
Citalopram usually is administered once daily in the morning or evening with or without food.
Citalopram hydrobromide tablets and capsules should be stored at a temperature of 20-25degreesC but may be exposed to temperatures ranging from 15-30degreesC.
Citalopram hydrobromide oral solution should be stored at 20-25degreesC but may be exposed to temperatures ranging from 15-30degreesC.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
In vitro studies indicate that cytochrome P-450 (CYP) 3A4 and CYP2C19 are the principal isoenzymes involved in the metabolism of citalopram.
In vitro enzyme inhibition data did not reveal an inhibitory effect of citalopram on CYP isoenzyme 3A4, 2C9, or 2E1 but did suggest that it is a weak inhibitor of 1A2, 2D6, and 2C19.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Current or recent (i.e., within 2 weeks) therapy with a monoamine oxidase (MAO) inhibitor, including IV methylene blue or linezolid, because of an increased risk of serotonin syndrome.
*Concurrent pimozide therapy because of risk of QT-interval prolongation.
*Known hypersensitivity to citalopram or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effect reported in >=5% of adult males and twice as often as in those receiving placebo is ejaculation disorder, primarily ejaculation delay.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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The manufacturer of citalopram states that the safety and efficacy of citalopram in pediatric patients have not been established. Two placebo-controlled trials involving 407 children and adolescents with major depressive disorder have been conducted with citalopram; the results of these trials were not sufficient to support use of the drug in pediatric patients with this condition.
Antidepressants such as citalopram have been shown to increase the risk of suicidal thoughts and behaviors in pediatric patients. Decreased appetite and weight loss have been observed in pediatric patients receiving SSRIs.
A pregnancy registry is available that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers can register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/.
Published observational data have shown that exposure to SSRIs, particularly during the month before delivery, is associated with a <2-fold increased risk of postpartum hemorrhage.
Available epidemiologic data and postmarketing reports from citalopram use during pregnancy have not established a drug-associated risk of major birth defects or miscarriage. Published data indicate that citalopram levels in cord blood and amniotic fluid are similar to those observed in maternal blood. Exposure to SSRIs during pregnancy increases the risk of persistent pulmonary hypertension of the newborn (PPHN) and/or poor neonatal adaptation; however, there are also risks associated with untreated depression during pregnancy.
Animal reproductive data have shown adverse embryo/fetal effects at doses that caused maternal toxicity.
Some neonates exposed to citalopram and other SSRIs late in the third trimester of pregnancy have developed complications that have sometimes been severe and required prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Clinical findings reported to date in the neonates have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These clinical features appear to be consistent with either a direct toxic effect of the SSRI or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture was consistent with serotonin syndrome.
Infants exposed to SSRIs in late pregnancy may have an increased risk of PPHN. PPHN is associated with significant morbidity and mortality and occurs in an estimated 1-2 infants per 1000 births in the general population.
In a prospective longitudinal study of 201 women with a history of major depressive disorder, those who discontinued their antidepressant medication during pregnancy were more likely to have a relapse of depression than women who continued to receive their antidepressant therapy while pregnant. Consider the risk of untreated depression when discontinuing or changing antidepressant therapy during pregnancy and postpartum.
Citalopram has been reported in human milk at relative infant doses ranging from 0.7-9.4% of the maternal weight adjusted dosage with a milk/plasma ratio that ranged from 0.78-4.3. Some infants exposed to citalopram through breastmilk developed irritability, restlessness, excessive somnolence, decreased feeding, and weight loss. The effects of citalopram on milk production are not known.
Women should be advised to notify their clinician if they plan to breast-feed. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for citalopram and any potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition. Breast-fed infants should be monitored for adverse effects such as irritability, restlessness, excessive somnolence, decreased feeding, and weight loss.
In geriatric patients >60 years of age, the maximum recommended citalopram dosage is 20 mg once daily. The manufacturer of the capsules states that citalopram capsules are not recommended in geriatric patients because the capsules are available only in a 30-mg strength and dosage adjustments are not possible.
Pharmacokinetic studies have revealed higher AUC values and longer elimination half-lives in geriatric patients >=60 years of age compared with younger individuals. Therefore, a maximum citalopram dosage of 20 mg once daily is recommended for geriatric patients >=60 years of age. The manufacturer of the capsules states that citalopram capsules are not recommended in geriatric patients because the capsules are only available in a 30-mg strength and dosage adjustments are not possible.
In pooled data analyses, a reduced risk of suicidality was observed in adults >=65 years of age on antidepressant therapy compared with placebo.
Geriatric patients may be more likely than younger patients to develop clinically significant citalopram-induced hyponatremia.
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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