Citalopram - Drug Monograph

Introduction

Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant approved by the FDA in 1998. It is widely prescribed for the treatment of major depressive disorder and various anxiety disorders. As one of the most selective SSRIs, citalopram exerts its therapeutic effects primarily through serotonin reuptake inhibition with minimal effects on other neurotransmitter systems.

Mechanism of Action

Citalopram exerts its antidepressant effects through potent and selective inhibition of serotonin reuptake in the presynaptic neuron. The drug binds to the serotonin transporter (SERT) protein, preventing the reuptake of serotonin into presynaptic neurons. This action increases serotonin concentration in the synaptic cleft, enhancing serotonergic neurotransmission.

The drug has negligible affinity for adrenergic (α₁, α₂, β), dopaminergic, histaminergic, muscarinic, and serotonin receptors (5-HT₁ₐ, 5-HT₂). Its high selectivity contributes to a favorable side effect profile compared to older antidepressant classes.

Indications

• Major depressive disorder (MDD)
• Off-label uses:
• Generalized anxiety disorder (GAD)
• Panic disorder
• Obsessive-compulsive disorder (OCD)
• Post-traumatic stress disorder (PTSD)
• Premenstrual dysphoric disorder (PMDD)
• Social anxiety disorder

Dosage and Administration

• 20 mg once daily, preferably in morning or evening
• May increase to 40 mg daily after at least one week
• Maximum recommended dose: 40 mg/day

• Geriatric patients: Maximum 20 mg/day due to reduced clearance
• Hepatic impairment: Maximum 20 mg/day
• Renal impairment: No dosage adjustment needed for mild-moderate impairment; use caution in severe impairment
• CYP2C19 poor metabolizers: Maximum 20 mg/day

• May be taken with or without food
• Tablets should be swallowed whole
• Therapeutic effects typically appear within 1-4 weeks

Pharmacokinetics

• Well absorbed orally
• Absolute bioavailability: 80%
• Time to peak concentration: 2-4 hours
• Food does not significantly affect absorption

• Volume of distribution: 12-17 L/kg
• Protein binding: Approximately 80%
• Crosses blood-brain barrier and placenta

• Primarily hepatic via CYP3A4 and CYP2C19
• Demethylated to active metabolite desmethylcitalopram
• Desmethylcitalopram has 50% of parent drug's potency

• Half-life: 35 hours (citalopram); 65 hours (desmethylcitalopram)
• Excretion: Primarily renal (20% as unchanged drug)
• Steady state achieved within approximately one week

Contraindications

• Hypersensitivity to citalopram or any component of the formulation
• Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation
• Concurrent use with pimozide
• Known congenital long QT syndrome

Warnings and Precautions

• Increased risk of suicidal thinking and behavior in children, adolescents, and young adults (ages 18-24) during initial treatment

• Dose-dependent QTc prolongation
• Avoid doses >40 mg/day
• Use caution in patients with risk factors for QT prolongation

• Risk particularly when used with other serotonergic drugs
• Requires immediate medical attention if suspected

• Taper gradually when discontinuing treatment
• Abrupt discontinuation may cause dizziness, nausea, irritability

• Bleeding risk (especially with concomitant NSAIDs, aspirin, warfarin)
• Hyponatremia (particularly in elderly)
• Activation of mania/hypomania in bipolar disorder
• Seizure risk (0.3% incidence)

Drug Interactions

• MAOIs: Risk of serotonin syndrome (contraindicated)
• Pimozide: Increased QTc prolongation (contraindicated)
• Other QTc-prolonging agents: Additive effects (quinidine, procainamide, amiodarone)
• Strong CYP2C19 inhibitors: Fluconazole, omeprazole (reduce citalopram dose)
• Serotonergic drugs: Tramadol, triptans, linezolid (increased serotonin syndrome risk)

• Warfarin: Increased anticoagulant effect
• NSAIDs/aspirin: Increased bleeding risk
• Cimetidine: Increased citalopram levels
• Metoprolol: Increased beta-blocker effects

Adverse Effects

• Nausea (21%)
• Dry mouth (20%)
• Somnolence (18%)
• Insomnia (15%)
• Increased sweating (11%)

• Fatigue
• Diarrhea
• Dyspepsia
• Anxiety
• Tremor
• Anorexia
• Ejaculation disorder
• Impotence

• QTc prolongation
• Serotonin syndrome
• Suicidal ideation
• Seizures
• Hyponatremia
• Abnormal bleeding
• Mania/hypomania

Monitoring Parameters

• Comprehensive metabolic panel (including sodium)
• ECG (in patients with cardiac risk factors)
• Pregnancy test if appropriate
• Suicide risk assessment
• Mood assessment scales (PHQ-9, GAD-7)

• Therapeutic response (weeks 4-8)
• Adverse effects (especially first 2 weeks)
• Serum sodium (in elderly and patients on diuretics)
• Bleeding signs/symptoms
• Mood changes, especially worsening depression or suicidal thoughts
• ECG if symptoms suggest arrhythmia or with dose increases

• Weight changes
• Periodic reassessment of continued need
• Withdrawal symptoms upon discontinuation

Patient Education

• Therapeutic effects may take 2-4 weeks to appear
• Do not stop abruptly; taper under medical supervision
• Take at same time each day
• Report any worsening depression, suicidal thoughts, or unusual behavior changes
• Avoid alcohol during treatment
• Use caution when driving or operating machinery until effects are known
• Report signs of serotonin syndrome (agitation, hallucinations, fever, tachycardia)
• Inform all healthcare providers about citalopram use, especially before surgery
• Use effective contraception; discuss pregnancy plans with provider
• Notify provider of any new medications, including OTC products

• Store at room temperature
• Keep in original container
• Dispose of unused medication properly

References

1. FDA Prescribing Information: Celexa (citalopram) [2023] 2. Stahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 4th ed. Cambridge University Press; 2013. 3. Hirsch M, Birnbaum RJ. Citalopram: A comprehensive review. UpToDate [2023] 4. Kelly K, Posternak M, Alpert JE. Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues Clin Neurosci. 2008;10(4):409-418. 5. Zivin K, Pfeiffer PN, Bohnert AS, et al. Evaluation of the FDA warning against prescribing citalopram at doses exceeding 40 mg. Am J Psychiatry. 2013;170(6):642-650. 6. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd ed. 2010. 7. Howland RH. A critical evaluation of the cardiac toxicity of citalopram: part 1. J Psychosoc Nurs Ment Health Serv. 2011;49(11):13-16. 8. Sánchez C, Reines EH, Montgomery SA. A comparative review of escitalopram, paroxetine, and sertraline: are they all alike? Int Clin Psychopharmacol. 2014;29(4):185-196.