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Antidepressant-Related Adverse Effects Improve with Time


Am Fam Physician. 2010 Apr 15;81(8):1030.

Background: Despite the safety and effectiveness of antidepressant therapy in older persons, many patients are not adequately treated. In a recent meta-analysis, researchers estimated that approximately 35 percent of depressed patients 65 years and older were receiving suboptimal dosages of antidepressants. Physicians may be reluctant to use higher dosages in older patients out of concern for a greater risk of adverse effects. Kok and colleagues examined the tolerability and course of antidepressant-related adverse effects in older persons.

The Study: The authors conducted a double-blind, randomized, 12-week trial among inpatients 60 years and older who were diagnosed with depression. Patients received nortriptyline (Pamelor) or venlafaxine (Effexor) for 12 weeks in a blinded fashion, and were then followed in an open study for the next three years. The presence and severity of adverse effects were periodically measured during the study. Patients were excluded if they had dementia or decreased mental status, an absolute contraindication to the study medications, or if they had previously been treated unsuccessfully with venlafaxine or a tricyclic antidepressant.

Results: A total of 81 patients were randomized; both groups had similar baseline traits. Patients received a mean dosage of 156 mg per day of venlafaxine or 94.5 mg per day of nortriptyline. Most patients initially experienced four to five adverse effects with either drug, which decreased to one to two effects after two to three years of treatment. No difference in type or number of adverse effects occurred between groups except for dry mouth, which was more common with nortriptyline (initial incidence of 87.8 percent versus 50 percent with venlafaxine). Antidepressant dosage was not associated with the number of adverse effects, although there was a correlation with the severity of adverse effects. The severity of all adverse effects gradually decreased in a similar fashion for both groups as the study progressed (e.g., 43 percent of the nortriptyline group still had dry mouth by the end of the study).

Conclusion: The authors conclude that older persons generally tolerate nortriptyline and venlafaxine well. In this trial, antidepressant dosage correlated with severity but not the number of adverse effects, and both number and severity of these effects decreased over the three-year study period.


Kok RM, et al. The course of adverse effects of nortriptyline and venlafaxine in elderly patients with major depression. J Am Geriatr Soc. November 2009;57(11):2112–2117.



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