What is the medication profile for citalopram (Selective Serotonin Reuptake Inhibitor - SSRI)?

Medication Profile for Citalopram (SSRI)

Citalopram is a highly selective serotonin reuptake inhibitor (SSRI) that is effective for treating major depressive disorder with a generally favorable side effect profile compared to older antidepressants. 1

Mechanism of Action

• Citalopram works by potentiating serotonergic activity in the central nervous system through inhibition of neuronal reuptake of serotonin (5-HT) 1
• It is a racemic mixture (50/50), with the (S)-enantiomer primarily responsible for the inhibition of 5-HT reuptake 1
• Citalopram is highly selective for serotonin reuptake with minimal effects on norepinephrine and dopamine neuronal reuptake 1
• The drug has minimal affinity for other neurotransmitter receptors (5-HT1A, 5-HT2A, dopamine D1 and D2, adrenergic, histamine H1, GABA, muscarinic cholinergic, and benzodiazepine receptors) 1

Pharmacokinetics

• Peak blood levels occur approximately 4 hours after oral administration 1
• Absolute bioavailability is about 80%, and absorption is not affected by food 1
• The mean terminal half-life is approximately 35 hours 1
• Steady-state plasma concentrations are achieved within approximately one week of once-daily dosing 1
• Metabolism is primarily hepatic via CYP3A4 and CYP2C19 enzymes 1
• Citalopram is metabolized to demethylcitalopram (DCT), didemethylcitalopram (DDCT), citalopram-N-oxide, and a deaminated propionic acid derivative 1
• The metabolites are significantly less potent than the parent compound in inhibiting serotonin reuptake 1

Clinical Efficacy

• Citalopram is effective for the treatment of major depressive disorder (MDD) 2
• In clinical trials, citalopram doses of 40 mg/day and 60 mg/day showed significantly greater improvement than placebo on all efficacy measures 3
• Lower doses (10 mg/day and 20 mg/day) also showed consistent improvement relative to placebo 3
• Citalopram has similar efficacy to other SSRIs for the treatment of MDD 2
• Meta-analyses comparing citalopram with escitalopram showed slightly better efficacy for escitalopram (relative benefit 1.14,95% CI 1.04 to 1.26), though the clinical significance of this difference is questionable 2
• Citalopram appears more effective than paroxetine (OR 0.65,95% CI 0.44 to 0.96) and reboxetine (OR 0.63,95% CI 0.43 to 0.91) in achieving acute response 4

Quality of Life Impact

• Evidence from fair-quality efficacy trials shows no significant differences among second-generation antidepressants, including citalopram, in improving quality of life or functional capacity 2
• Citalopram, like other SSRIs, improves health-related quality of life including work, social and physical functioning, concentration and memory 2

Dosing

• The recommended starting dose is typically 20 mg once daily 1
• Dose can be increased to 40 mg daily after at least one week if clinically indicated 1
• For patients over 60 years of age, the maximum recommended dose is 20 mg/day due to the risk of QT prolongation 1
• For adolescents with depression, the recommended starting dose is 10 mg daily, which can be increased in 10 mg increments to an effective dose of 20 mg, with a maximum dosage of 60 mg 2

Adverse Effects

• Most common adverse effects include nausea, dry mouth, somnolence, insomnia, and increased sweating 3
• Approximately 15% of patients discontinue treatment due to adverse events 3
• Citalopram has a more favorable side effect profile than tricyclic antidepressants, with fewer anticholinergic effects 5
• Sexual dysfunction is a common side effect of citalopram and other SSRIs 2
• Risk of QT prolongation exists, particularly at doses exceeding 40 mg/day in adults or 20 mg/day in patients over 60 years 1
• Gastrointestinal bleeding risk is increased (OR = 1.2 to 1.5), especially with concurrent use of antiplatelet or nonsteroidal anti-inflammatory drugs 2
• Risk of hyponatremia (0.5% to 12% in older adults) is higher with SSRIs compared to other drug classes 2

Special Populations

Elderly Patients

• Citalopram AUC and half-life are increased in subjects ≥ 60 years of age by 23-30% and 30-50%, respectively 1
• Maximum recommended dose for patients over 60 years is 20 mg/day due to increased risk of QT prolongation 1
• Citalopram is considered one of the preferred agents for older patients with depression 2

Pregnancy and Breastfeeding

• Citalopram transfers in low concentrations into breast milk 2
• Paroxetine and sertraline are more commonly prescribed during breastfeeding than citalopram 2

Drug Interactions

• Concomitant administration with monoamine oxidase inhibitors (MAOIs) is contraindicated due to risk of serotonin syndrome 2
• Citalopram may interact with drugs that prolong the QT interval 2
• Citalopram may have a lower propensity for drug interactions compared to other SSRIs due to less effect on CYP450 isoenzymes 2
• Risk of serotonin syndrome when combined with other serotonergic medications 2
• Increased bleeding risk when used with antiplatelet drugs or NSAIDs 2

Treatment Duration

• Treatment for a first episode of major depression should last at least 4 months 2
• Patients with recurrent depression may benefit from prolonged treatment 2
• Continuation of antidepressant therapy reduces the risk for relapse 2

Monitoring

• Regular assessment of therapeutic response and adverse effects beginning within 1-2 weeks of initiation of therapy is recommended 2
• Monitor for emergence of suicidality, especially during the initial few months of treatment or at times of dose changes 2
• For patients who do not have an adequate response within 6-8 weeks, treatment modification should be considered 2

Clinical Pearls

• Citalopram has a more favorable tolerability profile than tricyclic antidepressants 5
• Withdrawal symptoms can occur with abrupt discontinuation; therefore, gradual tapering is recommended 2
• Antidepressants are most effective in patients with severe depression 2
• Approximately 38% of patients do not achieve treatment response during 6-12 weeks of treatment with second-generation antidepressants, and 54% do not achieve remission 2