What is the maximum recommended dose of citalopram (Selective Serotonin Reuptake Inhibitor - SSRI)?

Maximum Dose of Citalopram

The maximum recommended dose of citalopram is 40 mg per day for adults under 60 years of age, and 20 mg per day for adults 60 years and older due to the risk of QT interval prolongation. 1, 2

Standard Dosing Guidelines

• The initial recommended dose of citalopram is typically 10-20 mg per day, which can be increased after 1-2 weeks if clinical response is insufficient 1
• For adults under 60 years of age, the maximum recommended dose should not exceed 40 mg per day 1, 2
• For adults 60 years and older, the maximum recommended dose is limited to 20 mg per day due to increased risk of QT interval prolongation 1, 2
• The FDA has established these maximum doses based on evidence of dose-dependent QT interval prolongation 2

Special Population Considerations

• Elderly patients (>60 years): Maximum dose limited to 20 mg/day due to pharmacokinetic changes that result in 23-30% higher AUC and 30-50% longer half-life compared to younger adults 2
• Hepatic impairment: Maximum dose should not exceed 20 mg/day due to reduced hepatic clearance (37% reduction) and doubled half-life 2
• CYP2C19 poor metabolizers: Maximum dose should not exceed 20 mg/day due to 68% higher Cmax and 107% higher AUC 2
• Patients taking CYP2C19 inhibitors (e.g., omeprazole, cimetidine): Maximum dose should not exceed 20 mg/day due to increased citalopram levels 2

Clinical Efficacy at Different Doses

• Clinical studies have shown efficacy across the dose range of 10-60 mg/day 3, 4
• Doses of 40 mg/day and 60 mg/day demonstrated significantly greater improvement compared to placebo on all efficacy measures 3
• Lower doses (10-20 mg/day) also showed improvement relative to placebo, though with smaller effect sizes than higher doses 3, 4
• Despite evidence of greater efficacy at 60 mg/day in some studies, this dose is no longer recommended due to cardiac safety concerns 3, 5

Safety Considerations and QT Prolongation Risk

• In 2011/2012, regulatory bodies (FDA and Health Canada) issued warnings about dose-dependent QT interval prolongation with citalopram 5
• These warnings resulted in significant reductions in high-dose prescribing (64.8% decline in those <65 years and 33.6% in those ≥65 years) 5
• The risk of QT prolongation increases with:
  • Higher doses (>40 mg/day) 2, 5
  • Advanced age (>60 years) 2
  • Concomitant use of other QT-prolonging medications 2, 5
  • Hepatic impairment 2
  • CYP2C19 poor metabolism 2

Practical Prescribing Recommendations

• Start with 20 mg once daily for most adult patients 1, 6
• For elderly patients or those with hepatic impairment, start with 10 mg daily 1, 2
• Dose increases should occur no more frequently than once weekly 1
• Monitor for QT prolongation, especially when using maximum doses or in high-risk patients 2, 5
• Avoid combining with other medications that prolong QT interval or inhibit CYP2C19 2, 5

Common Pitfalls to Avoid

• Exceeding the maximum recommended dose despite evidence of greater efficacy at higher doses (60 mg) in some older studies 3, 5
• Failing to reduce the maximum dose in elderly patients, those with hepatic impairment, or CYP2C19 poor metabolizers 2
• Not considering drug interactions that may increase citalopram levels and QT prolongation risk 2, 5
• Abrupt discontinuation, which can lead to withdrawal symptoms; citalopram should be tapered gradually when discontinuing 1