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Cyclic antidepressant doses higher than 100 mg should be used cautiously due to increased risk of sudden cardiac death

Newer selective serotonin reuptake inhibitor (SSRI) antidepressants, which have minimal known cardiovascular effects, are usually the first medication choice for depression. However, tricyclic and other cyclic antidepressants (TCAs) are frequently prescribed for patients in whom SSRIs are ineffective or are not well tolerated. Also, TCAs may be prescribed in lower doses to treat other disorders such as sleep problems, migraine, and chronic pain.

In low doses (less than 100 mg of amitriptyline or its equivalent), neither SSRIs nor TCAs increase the risk of sudden cardiac death. However, use of higher dose TCAs does increase the risk of sudden cardiac death. Thus, such TCA doses should be used cautiously, particularly in patients with pre-existing cardiovascular disease or the elderly, concludes Wayne Ray, Ph.D., of the Vanderbilt University Center for Education and Research on Therapeutics (CERT). The study was supported in part by the Agency for Healthcare Research and Quality (HS10384). Dr. Ray and his colleagues used Tennessee Medicaid data and State death certificates to examine the association between antidepressant use and confirmed sudden cardiac deaths among Tennessee Medicaid patients aged 15 to 84 years. Overall, there were 1,487 confirmed sudden cardiac deaths.

Compared with nonusers of antidepressants, users of high- or low-dose SSRIs and current users of low-dose TCAs had similar rates of sudden cardiac death. However, patients currently taking TCA doses of 100 mg or greater had a 41 percent greater rate of sudden cardiac death, and those taking TCA doses of 300 mg or greater had a 2.5-fold greater rate than patients not taking antidepressants. There was no evidence that TCA doses lower than 100 mg increased the risk of sudden cardiac death in subgroups who already had elevated risk, such as the elderly or those with pre-existing cardiovascular disease.

See "Cyclic antidepressants and the risk of sudden cardiac death," by Dr. Ray, Sarah Meredith, M.B.B.S., M.Sc., Purushottam B. Thapa, M.B.B.S., and others, in the March 2004 Clinical Pharmacology & Therapeutics 75, pp. 234-241.

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