Celexa - Drug Monograph

Introduction

Celexa (citalopram hydrobromide) is a selective serotonin reuptake inhibitor (SSRI) antidepressant approved by the FDA in 1998. It is primarily indicated for the treatment of major depressive disorder (MDD) in adults. As one of the most commonly prescribed antidepressants, Celexa works by increasing serotonin availability in the central nervous system, which helps regulate mood, emotion, and behavior.

Mechanism of Action

Citalopram exerts its therapeutic effects through potent inhibition of serotonin reuptake at the presynaptic neuronal membrane. It selectively blocks the serotonin transporter (SERT), increasing synaptic concentrations of serotonin in the central nervous system. This enhanced serotonergic activity is believed to mediate its antidepressant effects. Citalopram has minimal affinity for other neurotransmitter receptors including adrenergic, dopaminergic, histaminergic, and muscarinic receptors, contributing to its favorable side effect profile compared to older antidepressants.

Indications

• FDA-approved:

- Major depressive disorder (MDD) in adults

• Off-label uses (supported by clinical evidence):

- Generalized anxiety disorder (GAD) - Panic disorder - Social anxiety disorder - Obsessive-compulsive disorder (OCD) - Post-traumatic stress disorder (PTSD) - Premenstrual dysphoric disorder (PMDD)

Dosage and Administration

• Initial dose: 20 mg once daily
• May increase to 40 mg once daily after at least one week
• Maximum recommended dose: 40 mg/day

• Hepatic impairment: Maximum 20 mg/day
• Elderly patients (≥60 years): Maximum 20 mg/day
• CYP2C19 poor metabolizers: Maximum 20 mg/day
• Renal impairment: No dosage adjustment necessary for mild to moderate impairment; use caution in severe impairment

• Administer once daily, morning or evening, with or without food
• Tablets should be swallowed whole with water
• Available as 10 mg, 20 mg, and 40 mg tablets

Pharmacokinetics

Contraindications

• Hypersensitivity to citalopram or any component of the formulation
• Use of monoamine oxidase inhibitors (MAOIs) concurrently or within 14 days of discontinuing Celexa
• Use of pimozide
• Congenital long QT syndrome or known QT interval prolongation

Warnings and Precautions

• Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults (ages 18-24) with major depressive disorder and other psychiatric disorders

• QT prolongation and torsade de pointes: Dose-dependent effect; maximum recommended dose is 40 mg/day
• Serotonin syndrome: Risk particularly when used with other serotonergic drugs
• Discontinuation syndrome: Abrupt discontinuation may cause withdrawal symptoms
• Activation of mania/hypomania: Screen patients for bipolar disorder
• Abnormal bleeding: Increased risk of bleeding events, especially with concomitant NSAIDs, aspirin, or other drugs affecting coagulation
• Hyponatremia: May occur due to SIADH, particularly in elderly patients
• Angle-closure glaucoma: May occur in patients with anatomically narrow angles

Drug Interactions

• MAOIs: Risk of serotonin syndrome (contraindicated)
• Other serotonergic drugs: Increased risk of serotonin syndrome (tramadol, triptans, other SSRIs/SNRIs, etc.)
• Drugs that prolong QT interval: Additive effects (antiarrhythmics, antipsychotics, antibiotics)
• CYP2C19 inhibitors: May increase citalopram levels (omeprazole, fluconazole, etc.)
• CYP3A4 inhibitors: May increase citalopram levels (ketoconazole, clarithromycin, etc.)

• Warfarin: May increase anticoagulant effect
• CNS depressants: Additive sedative effects
• Drugs metabolized by CYP2D6: Citalopram may inhibit metabolism of these drugs

Adverse Effects

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

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

• Suicidal ideation/behavior
• Serotonin syndrome
• QT prolongation
• Seizures
• Hyponatremia
• Abnormal bleeding
• Mania/hypomania
• Angle-closure glaucoma

Monitoring Parameters

• Mental status and suicidal ideation, especially during initiation and dose adjustments
• ECG monitoring in patients with cardiac risk factors or those receiving high doses
• Serum sodium levels in elderly patients and those on diuretics
• Bleeding parameters in patients on anticoagulant therapy
• Mood changes indicating possible manic episodes
• Height and weight in pediatric patients
• Clinical response and side effects at 4-8 week intervals

Patient Education

• Take medication exactly as prescribed; do not adjust dose without medical supervision
• Therapeutic effects may take 4-8 weeks to become apparent
• Do not abruptly discontinue medication due to risk of withdrawal symptoms
• Report any worsening depression, suicidal thoughts, or unusual behavior changes immediately
• Be aware of potential side effects and report concerning symptoms
• Avoid alcohol during treatment
• Inform all healthcare providers about Celexa use before starting new medications
• Use caution when driving or operating machinery until effects are known
• Notify physician if pregnancy is planned or suspected

References

1. FDA Prescribing Information: Celexa (citalopram hydrobromide) 2. Sánchez C, et al. Psychopharmacology (Berl). 2004;174(2):163-76 3. Kennedy SH, et al. J Clin Psychiatry. 2009;70 Suppl 4:1-46 4. Zivin K, et al. Am J Psychiatry. 2013;170(5):542-50 5. Howland RH. J Psychosoc Nurs Ment Health Serv. 2011;49(6):13-6 6. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 2010 7. Drugs@FDA: FDA Approved Drug Products 8. Micromedex Solutions: Citalopram Drug Information 9. Clinical Pharmacology [database online]: Citalopram 10. UpToDate: Citalopram: Drug Information