Citalopram Hydrobromide

Approved Indication:

• Major Depressive Disorder (MDD) in adults.

Clinically Accepted Off-label Uses:

• Generalized Anxiety Disorder (GAD)
• Panic Disorder, with or without agoraphobia
• Obsessive-Compulsive Disorder (OCD)
• Post-Traumatic Stress Disorder (PTSD)
• Premenstrual Dysphoric Disorder (PMDD)
• Social Anxiety Disorder (Social Phobia)
• Dysthymia (Persistent Depressive Disorder)

Adults (Major Depressive Disorder):

• Initial dose: 20 mg once daily.
• Maintenance dose: May increase to a maximum of 40 mg once daily after 1 week if needed.
• Dose adjustments: Use the lowest effective dose.

Elderly (≥60 years):

• Maximum dose: 20 mg/day due to increased QT prolongation risk.

Hepatic Impairment:

• Recommended dose: 20 mg/day maximum.

Renal Impairment:

• Mild to moderate impairment: No dosage adjustment usually required.
• Severe impairment: Use with caution; limited data available.

Pediatric Use:

• Not FDA-approved for patients <18 years; safety and efficacy not established.

Administration Route:

• Oral. May be taken with or without food.

Duration of Therapy:

• Acute treatment: Minimum 6–8 weeks.
• Maintenance: Continuation for several months or longer based on clinical response.

Citalopram is a selective serotonin reuptake inhibitor (SSRI) that exerts its antidepressant effect by inhibiting the presynaptic reuptake of serotonin (5-HT) in the central nervous system. This increases the availability of serotonin in the synaptic cleft, enhancing serotonergic neurotransmission in the brain. Citalopram has minimal effects on norepinephrine and dopamine reuptake and negligible affinity for muscarinic, histaminergic, and adrenergic receptors, which contributes to its relatively favorable side effect profile.

• Absorption: Well-absorbed orally with peak plasma concentrations reached in 2–4 hours.
• Bioavailability: Approximately 80%.
• Distribution: Volume of distribution ~12 L/kg; highly protein-bound (50–80%).
• Metabolism: Primarily metabolized in the liver via CYP3A4, CYP2C19, and to a lesser extent CYP2D6.
• Metabolites: Active metabolite includes desmethylcitalopram, though less potent.
• Elimination Half-life: Approximately 35 hours.
• Excretion: Excreted via urine (~12–23%) and feces (~10%) primarily as metabolites.

Pregnancy:

• FDA Category C (old classification): Risk cannot be ruled out. Animal studies have shown adverse effects; human data limited.
• Clinical note: Use only if clearly needed. Third-trimester use may lead to neonatal serotonin syndrome or withdrawal symptoms.

Lactation:

• Citalopram is excreted in breast milk in low concentrations.
• Risk to infants is low, but monitor for sedation, poor feeding, and irritability. Consider benefit-risk assessment when breastfeeding.

• Primary Class: Antidepressant
• Subclass: Selective Serotonin Reuptake Inhibitor (SSRI)
• Generation: Second-generation antidepressant

• Hypersensitivity to citalopram or any excipients
• Concomitant use of MAOIs (including linezolid or IV methylene blue)
• Concurrent use with pimozide
• QT interval prolongation or congenital long QT syndrome
• Uncorrected hypokalemia or hypomagnesemia

• Suicidality Risk: Increased risk of suicidal thoughts and behaviors, especially in adolescents and young adults.
• QT Prolongation: Dose-dependent risk; avoid doses >40 mg/day. Perform ECG monitoring in high-risk patients.
• Serotonin Syndrome: Risk increases with serotonergic drugs. Discontinue immediately if symptoms arise.
• Hyponatremia/SIADH: Particularly in elderly patients.
• Seizures: Use cautiously in individuals with seizure history.
• Bleeding Risk: Increased when combined with NSAIDs, aspirin, or anticoagulants.
• Angle-Closure Glaucoma: May precipitate in susceptible individuals.

Common (≥1%):

• Central Nervous System: Insomnia, drowsiness, dizziness, fatigue, anxiety
• Gastrointestinal: Nausea, dry mouth, constipation, diarrhea
• Sexual: Decreased libido, delayed ejaculation, anorgasmia
• General: Increased sweating, tremor

Less Common/Serious:

• QT prolongation, Torsades de Pointes
• Serotonin syndrome
• Hyponatremia
• Seizures
• Hepatic enzyme elevation
• Suicidal ideation (especially <25 years)

Major Interactions:

• MAOIs: Risk of serotonin syndrome; contraindicated.
• NSAIDs, aspirin, anticoagulants: Increased risk of bleeding.
• Pimozide, other QT-prolonging agents: Additive risk; avoid concurrent use.
• Linezolid, methylene blue: Risk of serotonin syndrome.

CYP450 Interactions:

• Metabolized primarily by CYP2C19 and CYP3A4
• CYP2C19 poor metabolizers: Higher plasma levels; dose adjustment may be required.
• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): Can increase citalopram levels.

Food & Alcohol:

• Food has no significant effect on absorption.
• Alcohol is not recommended; may worsen CNS depression.

• Dose restrictions revised by FDA (no more than 40 mg/day, or 20 mg/day in elderly) due to QT prolongation risk.
• 2022 updates in clinical practice emphasize careful ECG monitoring and electrolyte correction before starting in cardiac risk patients.
• Updated NICE guidance (UK): Recommends citalopram as a first-line antidepressant for moderate depression, with ECG monitoring when indicated.

• Temperature: Store at 20°C to 25°C (68°F to 77°F).
• Allowable excursions: 15°C to 30°C (59°F to 86°F).
• Humidity: Keep container tightly closed to protect from moisture.
• Light: Store in a light-resistant container.
• Form-specific notes:
• Oral solution: Protect from freezing; shake well before use.
• Tablets: Do not split unless scored.