What are the best antidepressants for older adults?

Best Antidepressants for Older Adults

For older adults with depression, start with sertraline, citalopram, or escitalopram at 50% of standard adult doses, while strictly avoiding paroxetine and fluoxetine. 1, 2, 3

First-Line Preferred Agents

The American Academy of Family Physicians identifies six preferred antidepressants for older adults based on favorable adverse effect profiles: 1

• Sertraline (Zoloft): Start 25-50 mg daily, target 50-200 mg daily 2, 4, 5
• Citalopram (Celexa): Start 10 mg daily, maximum 20 mg/day in adults >60 years due to dose-dependent QT prolongation 2, 3
• Escitalopram (Lexapro): Start 5-10 mg daily, target 10-20 mg daily 1, 2, 3
• Mirtazapine (Remeron): Start 7.5-15 mg at bedtime, particularly useful when insomnia or poor appetite are prominent 1, 2, 6
• Venlafaxine (Effexor): Start at 50% adult dose, useful when cognitive symptoms are prominent 1, 2, 3
• Bupropion (Wellbutrin): Start 100-150 mg daily, preferred when fatigue or apathy dominate the clinical picture 1, 2, 3

Among these options, sertraline and citalopram receive the highest ratings for both efficacy and tolerability in older adults. 3, 7, 8 Sertraline has a particular advantage due to its minimal cytochrome P450-mediated drug interactions, which is critical in older adults taking multiple medications. 4, 5

Antidepressants to Strictly Avoid

Paroxetine must not be used in older adults due to significantly higher anticholinergic effects that can cause confusion, urinary retention, constipation, and falls. 1, 2, 3

Fluoxetine should be avoided due to its long half-life (increasing drug interaction risk), greater potential for agitation and overstimulation, and unsuitability for patients with dementia. 1, 2, 3

Tertiary-amine tricyclic antidepressants (amitriptyline, imipramine) are potentially inappropriate medications per the American Geriatric Society's Beers Criteria due to severe anticholinergic burden and cardiac conduction effects. 1, 3

Critical Dosing Strategy: "Start Low, Go Slow"

Always initiate treatment at approximately 50% of standard adult starting doses because older adults have slower drug metabolism and significantly greater risk of adverse drug reactions. 1, 2, 3 Titrate gradually every 1-2 weeks as tolerated. 6

Essential Safety Monitoring

Hyponatremia Risk

SSRIs cause clinically significant hyponatremia in 0.5-12% of elderly patients, typically within the first month of treatment. 2 Monitor sodium levels at baseline and within 2-4 weeks of initiation.

QT Prolongation with Citalopram

The FDA issued a 2012 boxed warning: never exceed 20 mg/day citalopram in patients >60 years due to dose-dependent QT prolongation risk. 2, 3 If higher doses are needed, switch to an alternative agent.

Gastrointestinal Bleeding

SSRIs increase GI bleeding risk (OR 1.2-1.5), which escalates dramatically with age: 4.1 hospitalizations per 1,000 adults aged 65-70 years versus 12.3 per 1,000 octogenarians. 3 When SSRIs are combined with NSAIDs, the risk multiplies 15-fold (adjusted OR 15.6). 3 Consider proton pump inhibitor prophylaxis if concurrent NSAID use is necessary.

Cardiac Considerations

Venlafaxine shows no association with cardiac arrest in registry studies, unlike SSRIs (OR 1.21) and tricyclics (OR 1.69). 3 Citalopram and escitalopram cause dose-dependent QT prolongation; monitor ECG if using higher escitalopram doses in patients >60 years. 3

Treatment Duration

Continue antidepressant treatment for 4-12 months after first episode of major depression. 1, 2, 3 For recurrent depression (≥2 episodes), consider prolonged treatment for 1-3 years or longer, as recurrence probability increases dramatically: 50% after first episode, 70% after second episode, 90% after third episode. 1, 2

Efficacy Evidence

Antidepressants double the likelihood of remission compared to placebo in older adults (OR 2.03,95% CI 1.67-2.46), with 36% achieving remission versus 21% on placebo. 3 Importantly, antidepressants are protective against suicidal behavior in adults ≥65 years (OR 0.06), contrasting sharply with increased risk in younger adults. 2, 3

Common Pitfalls to Avoid

• Do not use standard adult starting doses—always reduce by approximately 50% 1, 2, 3
• Do not prescribe paroxetine or fluoxetine as first-line agents 1, 2, 3
• Do not exceed 20 mg/day citalopram in patients >60 years 2, 3
• Do not combine SSRIs with NSAIDs without gastroprotection given the 15-fold increased bleeding risk 3
• Do not use tertiary-amine TCAs (amitriptyline, imipramine) due to severe anticholinergic and cardiac risks 1, 3