Citalopram Guidelines
Mario Davis
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[3-28-2012] The U.S. Food and Drug Administration (FDA) is clarifying dosing and warning recommendations for the antidepressant Celexa (citalopram hydrobromide; also available in generic form). In August 2011, FDA issued a Drug Safety Communication (DSC) stating that citalopram should no longer be used at doses greater than 40 mg per day because it could cause potentially dangerous abnormalities in the electrical activity of the heart.
Citalopram use at any dose is discouraged in patients with certain conditions because of the risk of QT prolongation, but because it may be important for some of those patients to use citalopram, the drug label has been changed to describe the particular caution that needs to be taken when citalopram is used in such patients. The revised drug label also describes lower doses that should be used in patients over 60 years of age.
Changes in the electrical activity of the heart (specifically, prolongation of the QT interval of the electrocardiogram [ECG]) can lead to a risk of an abnormal heart rhythm called Torsade de Pointes, which can be fatal. Patients at particular risk for developing prolongation of the QT interval include those with underlying heart conditions and those who are predisposed to having low levels of potassium and magnesium in the blood.
The citalopram drug label was revised on August 12, 2011 and again on March 27, 2012, to include new warnings about the potential for QT interval prolongation and Torsade de Pointes, as well as new drug dosage and usage recommendations. (See Additional Information for Healthcare Professionals).
FDA has received post-marketing reports of QT interval prolongation and Torsade de Pointes associated with Celexa (citalopram) and its generic equivalents. FDA evaluated the results of thorough QT studies assessing the effects of doses of citalopram and its active S-isomer escitalopram (Lexapro) on the QT interval in adults. Both studies are randomized, double-blind, placebo-controlled, crossover studies. In the citalopram study, 119 subjects received citalopram 20 mg/day and 60 mg/day, moxifloxacin 400 mg/day, and placebo. In the escitalopram study, 113 subjects received escitalopram 10 mg/day and 30 mg/day, moxifloxacin 400 mg/day, and placebo.
The summary of findings is presented in Table 1. As of March 27, 2012, this table has been updated to provide comparative information for escitalopram. Citalopram is a racemic mixture of S- and R-isomers. Escitalopram is the S-isomer of citalopram. The antidepressant activity of citalopram is limited to the S-isomer; therefore, each row of Table 1 shows equally effective doses of citalopram and escitalopram. The maximum recommended dose of escitalopram is 20 mg once daily.
Although the antidepressant effects of the drugs are known to be limited to the S-isomer, the difference between the effects of citalopram racemate and escitalopram on the QT interval presumably means that the QT effects are not specific to the S-isomer.
These studies show that citalopram causes dose-dependent QT interval prolongation that is clinically significant with the 60 mg daily dose. In addition, clinical trials do not show any added effectiveness of citalopram at 60 mg/day compared to 40 mg/day. Therefore, citalopram should not be used at doses above 40 mg per day. Important safety information about the potential for QT interval prolongation and Torsade de Pointes with updated drug dosage and usage recommendations have been added to the citalopram drug label. Given that these findings were not observed with escitalopram, there are no changes planned for escitalopram at this time.
Citalopram, a racemic mixture of R and S citalopram, is a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of major depressive disorder, panic disorder, and obsessive compulsive disorder. Escitalopram is the S enantiomer of citalopram indicated for major depressive episodes, panic disorder with or without agoraphobia, social anxiety disorder (social phobia), generalised anxiety disorder, and obsessive compulsive disorder.
The potential for citalopram and escitalopram to cause QT interval prolongation has been known for some time and is reflected in the product information. However, recent data have further defined this risk and have clarified that their effects on the QT interval are dose dependent. All available data have been subject to a Europe-wide review.
For both citalopram and escitalopram, elderly patients have a higher exposure due to age-related decline in metabolism and elimination. The maximum dose of both medicines has therefore been restricted in patients older than 65 years.
Cases of QT prolongation and ventricular arrhythmia, including Torsade de Pointes (TdP), have been reported via the Yellow Card Scheme with citalopram and escitalopram, mainly in women, those with hypokalaemia, or in those with pre-existing QT prolongation or other cardiac diseases.
Citalopram and escitalopram may have an additive effect to other drugs that prolong the QT interval. Coadministration of citalopram and escitalopram with medicines that prolong the QT interval is therefore contraindicated. These include:
Patients taking concomitant medications known to increase plasma levels of escitalopram and citalopram may require a dose reduction in light of these most recent QT data. Drugs known to increase plasma concentrations of escitalopram and citalopram include some antiretroviral medications, and omeprazole and cimetidine. Details of specific interactions can be found in individual Summaries of Product Characteristics (see the electronic Medicines Compendium).
Citalopram hydrobromide is a selective serotonin reuptake inhibitor. The primary FDA-approved clinical use for citalopram hydrobromide is for treating depression in adults. Off-label uses include alcohol use disorder, coronary arteriosclerosis, obsessive-compulsive disorder, panic disorder, postmenopausal flushing, and premenstrual dysphoric disorder. Citalopram is listed in the WHO model list of essential medicines to treat depressive disorders. Citalopram hydrobromide exerts its antidepressant action by potentiating serotonergic activity in the central nervous system. Multiple studies confirmed that citalopram hydrobromide is a selective serotonin reuptake inhibitor (SSRI) that has minimal effects on norepinephrine and dopamine neuronal reuptake. This activity reviews the indications, mechanism of action, administration, contraindications, monitoring, toxicity associated with citalopram, and the interprofessional team's role in caring for patients with conditions treated with citalopram.
Objectives:
- Identify the FDA-approved and off-label indications for citalopram.Apply evidence-based guidelines and recommendations when selecting citalopram as a treatment option.Assess patients for potential adverse effects associated with citalopram.Collaborate with mental health specialists, pharmacists, and other healthcare team members to optimize citalopram therapy and ensure the best outcomes with minimal adverse events.
Citalopram hydrobromide, the most selective serotonin reuptake inhibitor (SSRI), received FDA approval in 1998.[1] Citalopram is listed in the WHO model list of essential medicines to treat depressive disorders. According to the 2022 NICE (National Institute for Health and Care Excellence) guidelines, SSRIs should be considered the initial choice for pharmacotherapy in patients with depression.[2]
Citalopram hydrobromide exerts its antidepressant action by potentiating serotonergic activity in the central nervous system (CNS). Multiple studies confirm that citalopram hydrobromide, an SSRI, has minimal effects on norepinephrine and dopamine neuronal reuptake.[13] The drug has a low affinity for muscarinic acetylcholine receptors and mild antagonist action on histamine but no significant effect on alpha- or beta-adrenergic receptors or dopamine-1, dopamine-2, gamma-aminobutyric acid, opioid, or benzodiazepine receptors.[14][15] Citalopram is a racemic mixture of both (R)- and (S)-enantiomers, whereas escitalopram consists solely of the (S)-enantiomer.[16]
The neurotrophic hypothesis of depression emphasizes that depression results from reduced brain-derived neurotrophic factor (BDNF), leading to neuronal loss and reduced hippocampal neurogenesis. Antidepressants elevate BDNF levels, counteracting neuronal and cellular loss. Extensive research in both preclinical and clinical depression studies reveals reduced serum BDNF levels in depressed individuals. Antidepressants, including citalopram, raise the expression of BDNF in the hippocampus and preferential cortex.[17]
Citalopram is available in multiple oral dosage forms, including 10 mg, 20 mg, and 40 mg tablets taken once daily, as well as an oral solution with a concentration of 10 mg/5 mL. It is typically administered orally for adult patients younger than 60.
Patients who are at risk of experiencing significant adverse effects or overstimulation with citalopram should be started with the lowest recommended dosage. The dose should be increased gradually in 10-mg increments to optimize therapy. Anecdotal reports propose potential benefits of higher citalopram doses for individuals with OCD. Nevertheless, caution is advised, as dosages surpassing 40 mg daily are not recommended due to the associated risk of QT prolongation.[19][20][21]
Renal impairment: No dose adjustment is necessary for patients with mild-to-moderate renal impairment. Patients with severe renal impairments should be closely monitored for possible adverse reactions.
Pregnancy considerations: Citalopram is an FDA pregnancy category C drug. Citalopram is not an absolute contraindication in pregnancy but is not generally recommended, especially during the first trimester. Clinicians treating women with psychiatric conditions must inform the patient whether these medicines are needed during pregnancy.[22] Some reports associate SSRIs with persistent pulmonary hypertension of the newborn (PPHN).[23][24] Manufacturers report neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring respiratory support, tube feeding, and prolonged hospitalization.
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