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SSRIs and Medical Illness: The Good and the Bad

Citalopram seems effective for depressed cardiac patients, but SSRIs may increase risk for fractures in older people.

As the U.S. population ages, depressive illness and its treatments are increasingly complicated by comorbid medical illnesses and the medical risks of treatment. Two Canadian studies provide new insights.

In a 12-week, randomized, controlled study, researchers examined the efficacy of citalopram (20–40 mg/day), manual-based interpersonal psychotherapy, or both in 284 patients with depression (Hamilton Rating Scale for Depression score, 20) and with established, non-acute coronary artery disease. Citalopram produced significantly greater response (53% vs. 40%) and remission (36% vs. 22%) than did pill placebo. Interpersonal psychotherapy, either alone or combined with citalopram, was not better than clinical management. Effects of citalopram were greater in patients with recurrent than with first-episode depression. Citalopram was well tolerated. Serious adverse events in the entire sample were minimal.

In a 5-year, population-based, cohort study, other researchers assessed incident fractures among 5008 community-dwelling adults age 50 or older. Risk for "fragility fractures" (fractures after minimal trauma) was significantly associated with daily SSRI use, even after adjustment for multiple covariates, including age, comorbidities, and cumulative estrogen use. Respondents reporting daily SSRI use at baseline and at 5 years were significantly more likely as nonusers to have an incident fragility fracture (hazard rate, 2.1). SSRI use was associated with baseline low bone-mineral density at the hip and with history of falling, but these did not fully account for SSRI-associated fractures in the authors' estimation of risks.

Comment: These studies remind us of the benefits and risks of antidepressant treatment. In the first study, only medication was effective in treating depression in patients with cardiac disease. Interpersonal psychotherapy might have been ineffective because of ill patients’ difficulties in dealing with the higher demands of this treatment; the findings do not necessarily imply that other psychotherapies are ineffective. In the second study, the risk for fracture might result not only from SSRI-associated falling or decreases in bone-mineral density but also, perhaps, from some other aspect of SSRIs, such as effects on bone quality.

— Peter Roy-Byrne, MD

Published in Journal Watch Psychiatry February 5, 2007

Citation(s):

Lespérance F et al. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. JAMA 2007 Jan 24/31; 297:367-79.

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Richards JB et al. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med 2007 Jan 22; 167:188-94.

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• Medline abstract (Free)