What is the recommended approach for treating depression in the elderly?

Treatment of Depression in Elderly Patients

Start with sertraline, citalopram, or escitalopram at 50% of standard adult doses as first-line pharmacotherapy for depression in older adults, avoiding paroxetine and fluoxetine due to their unfavorable safety profiles in this population. 1, 2

First-Line Antidepressant Selection

Preferred SSRIs

• Sertraline receives the highest rating for both efficacy and tolerability in older adults and should be considered the optimal first choice 2, 3
• Sertraline has identical pharmacokinetics in elderly versus younger patients, eliminating concerns about age-related drug accumulation 4
• Citalopram (maximum 20 mg/day in adults >60 years) and escitalopram are equally preferred first-line options 1, 2
• Sertraline has the lowest potential for cytochrome P450-mediated drug interactions among SSRIs, which is critical given polypharmacy in elderly patients 3, 5, 4

Alternative First-Line Agents

• Venlafaxine (SNRI) is equally preferred as first-line therapy, particularly when cognitive symptoms are prominent 1, 2
• Bupropion is valuable when cognitive symptoms dominate, as it has dopaminergic/noradrenergic effects with lower rates of cognitive side effects 1, 2
• Mirtazapine is also recommended as a first-line option 1

Antidepressants to Avoid

• Never use paroxetine in older adults due to significantly higher anticholinergic effects and sexual dysfunction rates 1, 2
• Never use fluoxetine due to its long half-life, greater risk of drug interactions, and potential for agitation and overstimulation in this age group 1, 2
• Avoid tricyclic antidepressants (especially tertiary-amine TCAs like amitriptyline and imipramine) due to severe anticholinergic effects and designation as potentially inappropriate medications per Beers Criteria 1, 2

Dosing Strategy

Starting Doses

• Always start at approximately 50% of standard adult doses due to slower metabolism and increased sensitivity to adverse effects in older adults 1, 2
• For sertraline, start at 50 mg/day (the same starting dose as younger adults, but this represents the optimal therapeutic dose for elderly patients) 6
• For citalopram, start at 10-20 mg/day with a strict maximum of 20 mg/day in adults >60 years due to dose-dependent QT prolongation risk 1, 2
• For venlafaxine, reduce the total daily dose by 50% in elderly patients, starting at 37.5 mg/day 7

Dose Titration

• Follow a "start low, go slow" approach when increasing doses 1
• For sertraline, if inadequate response after 2-4 weeks, increase in 50 mg increments at weekly intervals to maximum 200 mg/day 6
• For venlafaxine, increase in increments of up to 75 mg/day at intervals of no less than 4 days 7

Efficacy Evidence

• Antidepressants double the likelihood of remission compared to placebo (OR 2.03,95% CI 1.67-2.46), with 36% achieving remission versus 21% on placebo 2
• Second-generation antidepressants show no differences in efficacy based on age, with elderly patients responding as well as younger patients 8
• Psychotherapy is equally effective, with treated older adults more than twice as likely to achieve remission compared to no treatment (OR 2.47-2.63) 2

Critical Safety Considerations

Protective Effects

• Antidepressants are actually protective against suicidality in adults ≥65 years (OR 0.06,95% CI 0.01-0.58), contrasting sharply with increased risk in younger adults 1, 2

Major Safety Risks

Gastrointestinal Bleeding:

• Upper GI bleeding risk increases substantially with age when using SSRIs: 4.1 hospitalizations per 1,000 adults aged 65-70 years and 12.3 hospitalizations per 1,000 octogenarians 2
• Risk multiplies dramatically (adjusted OR 15.6) when SSRIs are combined with NSAIDs 2
• Never combine SSRIs with NSAIDs without gastroprotection given the 15-fold increased bleeding risk 2

Hyponatremia:

• SSRIs are associated with clinically significant hyponatremia in 0.5-12% of elderly patients, typically occurring within the first month of treatment 1
• Elderly patients are at greater risk for this adverse event 7

QT Prolongation:

• Citalopram carries a 2012 FDA boxed warning: do not exceed 20 mg/day in adults older than 60 years due to dose-dependent QT prolongation 1, 2

Treatment Duration

• Continue treatment for 4-12 months after first episode of major depressive disorder 1, 2
• For patients with recurrent depression, longer treatment periods are beneficial 1
• The probability of recurrence increases with each episode: 50% after first episode, 70% after second, 90% after third 1
• Continued treatment after remission protects against recurrence 2

Discontinuation Strategy

• Gradually taper over several weeks rather than abrupt cessation to minimize discontinuation symptoms 7
• Monitor for discontinuation symptoms including respiratory distress, irritability, and mood changes 7
• If intolerable symptoms occur, resume the previously prescribed dose and taper more gradually 7

Monitoring Requirements

• Assess depression symptoms biweekly or monthly until remission using validated tools like PHQ-9 9
• Monitor for hyponatremia especially in the first month of treatment 1
• Assess for bleeding risk, especially if patient takes NSAIDs or anticoagulants 2
• Track both mood and cognitive symptoms using standardized measures 2
• Monitor blood pressure if using venlafaxine, as sustained hypertension can occur 7

Special Dosing Adjustments

Hepatic Impairment

• Reduce total daily dose by 50% in patients with mild to moderate hepatic impairment 7
• May need to reduce dose even more than 50% due to individual variability 7

Renal Impairment

• Reduce total daily dose by 25% in patients with mild to moderate renal impairment (GFR 10-70 mL/min) 7
• Reduce total daily dose by 50% in patients undergoing hemodialysis 7

Common Pitfalls to Avoid

• Do not use standard adult starting doses—always reduce by approximately 50% 2
• Do not prescribe paroxetine or fluoxetine as first-line agents in older adults 2
• Do not combine SSRIs with NSAIDs without gastroprotection given the 15-fold increased bleeding risk 2
• Do not use tertiary-amine TCAs (amitriptyline, imipramine) due to severe anticholinergic burden 2
• Do not exceed citalopram 20 mg/day in patients >60 years 1, 2
• Do not assume depression in elderly patients with dementia will respond to antidepressants—high-quality evidence does not support pharmacologic treatment of depression in patients with dementia 10