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Am Fam Physician. 2006;74(9):1503

Antidepressants in Older Persons

Clinical Question

Which antidepressants are effective and well tolerated in older persons with depression?

Evidence-Based Answer

In older persons with depression, three classes of antidepressants are equally effective: selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and tricyclic-like compounds. More patients taking classic tricyclic antidepressants stopped their medications because of adverse events than did those taking SSRIs. Tricyclic-like medications had withdrawal rates similar to SSRIs, but the studies were small. The strongest evidence supports using SSRIs as first-line pharmacotherapy in older patients with depression.

Practice Pointers

Depression is estimated to affect 17 to 37 percent of the population older than 55 years.1 Despite its high prevalence in a rapidly growing segment of the U.S. population, depression still is underdiagnosed.2 In older persons, it can be difficult to diagnose because medical illnesses and dementia can cause symptoms of depression. In 2001, a Cochrane review concluded that antidepressant medications are effective in older patients and those with severe medical illness.1 However, choice of medication inolder patients must account for decreased renal and hepatic function and the potential for adverse reactions and drug interactions,2 and it depends on medical comorbidities and patient and physician preference.

Mottram and colleagues reviewed the literature to determine which antidepressants are effective and well tolerated in older patients. They found 29 trials. Six trials, with a total of 843 participants, compared all tricyclic antidepressants with all SSRIs. There was no difference in effectiveness. Eleven trials (with 1,091 patients) measuring withdrawal rates showed that patients taking SSRIs were less likely to withdraw than patients taking tricyclic antidepressants, in general (relative risk [RR] = 1.24; 95% confidence interval [CI], 1.04 to 1.47) and because of side effects (RR = 1.30; 95% CI, 1.02 to 1.64). Patients taking SSRIs also were less likely to withdraw than patients taking tricyclic-like compounds, but the studies were small.

When starting antidepressant treatment in older patients, most family physicians make a medication choice based on effectiveness and tolerability. In most situations, SSRIs are the initial medication chosen for major or minor depression because of their good effectiveness and tolerable side-effect profile. In some situations, such as treatment resistance or medical conditions that would benefit from a different class of medications, comorbidities may dictate another choice (e.g., use of a tricyclic antidepressant in a patient with peripheral neuropathy).

The Cochrane study reaffirms that patients will benefit from SSRIs, but also that, if the situation is appropriate, tricyclic and atypical antidepressants will benefit patients as well. If a patient is warned in advance about potential side effects, withdrawal because of the side effects may be less likely.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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