What is the recommended approach for managing depression in individuals over 65?

Management of Depression in Individuals Over 65

Start with citalopram or sertraline at 50% of standard adult doses as first-line pharmacotherapy, combined with psychotherapy (cognitive-behavioral or interpersonal therapy) for optimal outcomes. 1

First-Line Pharmacologic Treatment

Preferred Agents

• Citalopram and sertraline receive the highest ratings for both efficacy and tolerability in older adults according to the American Academy of Family Physicians 1
• Start at approximately 50% of standard adult doses due to slower metabolism and increased sensitivity to adverse effects 1
• Venlafaxine (SNRI) is equally preferred as first-line therapy, particularly when cognitive symptoms are prominent 1
• Bupropion is valuable when cognitive symptoms dominate, as it has dopaminergic/noradrenergic effects with lower rates of cognitive side effects 1

Agents to Avoid

• Paroxetine should NOT be used due to significantly higher anticholinergic effects and sexual dysfunction rates 1
• Fluoxetine should be avoided due to greater risk of agitation and overstimulation, plus its long half-life makes it unsuitable for older adults 2, 1
• Tertiary-amine TCAs (amitriptyline, imipramine) are potentially inappropriate per Beers Criteria due to severe anticholinergic effects 1
• Antidepressants with anticholinergic burden should be avoided, especially in patients with frailty and dementia 2

Non-Pharmacologic Interventions

Essential Components

• Combine antidepressant medication with psychotherapy for optimal outcomes 1, 3
• Psychotherapy is equally effective as pharmacotherapy, with treated older adults more than twice as likely to achieve remission (OR 2.47-2.63) 1
• Preferred psychotherapy techniques include cognitive-behavioral therapy, supportive psychotherapy, problem-solving psychotherapy, and interpersonal psychotherapy 3

Additional Interventions

• Exercise programs can alleviate depressive symptoms and improve mental health 2
• Behavioral interventions should be incorporated 2
• Address social isolation and loneliness through referral to local social assistance programs 2
• Optimize nutrition and encourage social engagement 2

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 1
• Second-generation antidepressants show no differences in efficacy based on age, with elderly patients responding as well as younger patients 1
• Sertraline is as effective as fluoxetine, nortriptyline, and imipramine in elderly patients 4, 5

Critical Safety Considerations

Protective Effects

• Antidepressants appear protective against suicidal behavior in adults over 65 (OR 0.06,95% CI 0.01-0.58), contrasting sharply with increased risk in younger adults 1

Bleeding Risk

• 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 1
• Risk multiplies dramatically (adjusted OR 15.6) when SSRIs are combined with NSAIDs 1
• Do NOT combine SSRIs with NSAIDs without gastroprotection 1

Hyponatremia

• SSRIs have been associated with clinically significant hyponatremia in elderly patients, who may be at greater risk 6

Drug Interactions

• Sertraline has a low potential for drug interactions at the cytochrome P450 enzyme system level, making it advantageous in elderly patients who typically receive multiple medications 4, 5

Treatment Duration

• Continue treatment for 4-12 months after first episode of major depressive disorder 1
• For patients with 2 episodes, continue for 1-3 years 3
• For 3 or more episodes, continue for longer than 3 years 3
• Continued treatment after remission protects against recurrence 1

Monitoring Requirements

• Assess for bleeding risk, especially if patient takes NSAIDs or anticoagulants 1
• Track both mood and cognitive symptoms using standardized measures 1
• Screen for depression using short and simple tools 2
• Regular monitoring of weight is recommended if treatment is continued long-term 6
• Monitor for serotonin syndrome, particularly if combining with other serotonergic medications 7

Special Populations

Patients with Dementia and Frailty

• Provide treatments considering risk of adverse effects, comorbidities, and behavioral/psychological symptoms 2
• Among SSRIs, fluoxetine is generally not recommended due to long half-life and side effects 2
• Venlafaxine, vortioxetine, and mirtazapine are safer options in terms of drug interactions 2
• Interventions targeting frailty (physical activity, nutrition, social engagement, cognitive stimulation) can also reduce depressive symptoms 2

Patients with Medical Comorbidities

• Vascular morbidity, diabetes mellitus, or arthritis does not affect the antidepressant effect of sertraline 4, 5
• Treat both depression and contributing medical conditions from the outset 3

Common Pitfalls to Avoid

• Do NOT use standard adult starting doses—always reduce by approximately 50% 1
• Do NOT prescribe paroxetine or fluoxetine as first-line agents 1
• Do NOT combine SSRIs with NSAIDs without gastroprotection given the 15-fold increased bleeding risk 1
• Do NOT use tertiary-amine TCAs due to severe anticholinergic burden 1
• Do NOT avoid antidepressant therapy simply because of patient's age 8