How should citalopram be dosed in adults, including initial dose, titration, maximum dose, and adjustments for patients aged 60 years or older, hepatic impairment, renal impairment, and QT‑interval prolongation risk?

Citalopram Dosing Guidelines

For most adults, start citalopram at 20 mg once daily and increase to a maximum of 40 mg/day after at least one week; however, patients over 60 years, those with hepatic impairment, CYP2C19 poor metabolizers, or those taking CYP2C19 inhibitors should not exceed 20 mg/day due to dose-dependent QT prolongation risk. 1

Standard Adult Dosing (Age ≤60 Years)

• Initial dose: 20 mg once daily 1
• Titration: May increase to 40 mg/day after a minimum of one week if clinically indicated 1
• Maximum dose: 40 mg/day (do not exceed this dose due to QT prolongation risk) 1
• Time to steady state: Approximately one week with once-daily dosing 1
• Peak plasma levels: Occur approximately 4 hours after oral administration 1

Dose Reductions for High-Risk Populations

Patients ≥60 Years Old

Maximum dose is 20 mg/day in elderly patients due to significantly increased drug exposure and QT prolongation risk. 1

• Citalopram AUC increases by 23-30% and half-life increases by 30-50% in patients ≥60 years 1
• The European Medicines Agency specifically recommends starting at 10 mg daily in elderly patients, with a maximum of 10 mg daily due to QT prolongation risk 2
• Elderly patients often have multiple cardiac risk factors that compound arrhythmia risk 2

Hepatic Impairment

Maximum dose is 20 mg/day in patients with any degree of hepatic impairment. 1

• Oral clearance decreases by 37% and half-life doubles (from 36.8 to 83.4 hours) in cirrhotic patients 1, 3
• Even moderate hepatic dysfunction warrants dose reduction 3
• Standard liver function tests (galactose elimination capacity, Child-Pugh score) are poor predictors of citalopram pharmacokinetic changes, so apply the 20 mg maximum universally in hepatic disease 3

Renal Impairment

No dose adjustment is required for mild to moderate renal impairment (creatinine clearance ≥20 mL/min). 1

• Oral clearance decreases by only 17% in moderate renal impairment 1, 3
• Renal clearance accounts for <20% of total citalopram elimination 1, 3
• Severe renal failure (creatinine clearance <20 mL/min): No pharmacokinetic data are available; use with extreme caution and consider alternative agents 1, 3

CYP2C19 Poor Metabolizers

Maximum dose is 20 mg/day in CYP2C19 poor metabolizers. 1

• Steady-state Cmax increases by 68% and AUC increases by 107% in poor metabolizers 1
• CYP2C19 is one of the two primary enzymes metabolizing citalopram (along with CYP3A4) 1

Patients Taking CYP2C19 Inhibitors

Maximum dose is 20 mg/day when citalopram is co-administered with cimetidine or other potent CYP2C19 inhibitors (e.g., omeprazole). 1

• Potent CYP2C19 inhibitors decrease citalopram clearance, increasing QT prolongation risk 1
• CYP3A4 inhibitors (ketoconazole, itraconazole, macrolides) do not significantly affect citalopram pharmacokinetics and do not require dose adjustment 1

QT Interval Prolongation: The Critical Safety Concern

All dose restrictions above 20 mg/day are driven by dose-dependent QT interval prolongation and risk of torsades de pointes. 1, 4, 5, 6

Baseline Screening Before Initiating Citalopram

• Obtain baseline ECG in all patients, especially those ≥60 years, with cardiac disease, electrolyte abnormalities, or taking other QT-prolonging drugs 4
• Screen family history for sudden cardiac death or long QT syndrome 4
• Check serum potassium and magnesium; correct abnormalities before starting citalopram 4, 5

Monitoring During Treatment

• Perform routine ECG monitoring during therapy, particularly in elderly patients with polypharmacy 4, 7
• Even FDA-recommended doses (≤40 mg in adults ≤60 years, ≤20 mg in elderly) can cause significant QT prolongation in elderly comorbid patients with multiple medications 7
• Absolute contraindication: Patients with congenital long QT syndrome should not receive citalopram 4

Clinical Context of QT Risk

• Among SSRIs, citalopram prolongs the QT interval most significantly 7
• QT prolongation is small and relatively safe in young, healthy individuals 7
• No cases of sudden cardiac death have been reported in patients taking ≤60 mg/day who are free of QT risk factors 6
• However, case reports document torsades de pointes at therapeutic doses (400 mg overdose, but also at lower doses in vulnerable patients) 4, 5

Common Pitfalls and How to Avoid Them

1. Prescribing >20 mg/day in elderly patients: This is the most common error. Always verify age before titrating above 20 mg 1

2. Ignoring hepatic impairment: Even mild cirrhosis doubles citalopram half-life; cap at 20 mg/day 1, 3

3. Failing to check for CYP2C19 inhibitors: Omeprazole, cimetidine, and other proton-pump inhibitors are commonly co-prescribed and mandate 20 mg maximum 1

4. Skipping baseline ECG in high-risk patients: Elderly patients, those with cardiac history, or those on multiple medications require ECG before and during treatment 4, 7

5. Combining with other QT-prolonging drugs: Avoid co-administration with antipsychotics (e.g., risperidone), macrolide antibiotics, or antiarrhythmics without cardiology consultation 8

Absorption and Administration

• Bioavailability: 80% (not affected by food) 1
• Timing: Can be taken with or without food at any time of day 1
• Steady state: Achieved in approximately one week; plasma concentrations accumulate 2.5-fold at steady state 1

When Citalopram Is Not the Best Choice

• Elderly patients with polypharmacy: Consider escitalopram (the S-enantiomer) at lower doses or alternative SSRIs with less QT risk 7
• Patients with cardiac risk factors: Sertraline or fluoxetine may be safer alternatives 7
• Efficacy consideration: Recent data show citalopram is not more effective than other SSRIs, so the QT risk may not be justified in high-risk populations 7