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Antidepressants – Risk vs. Benefit

According to Vice Chair in the Department of Psychiatry and Behavioral Sciences and Director of Child and Adolescent Psychiatry at the University of Texas Medical Branch at Galveston, Karen Dineen Wagner, M.D. states that two recent publications by Gibbons and colleagues have provided the medical community with information regarding the risk to benefit ratio of antidepressants for the treatment of major depressive disorder (MDD) in youth, adults, and elderly.[1] Wagner discusses such in her article “Antidepressants: Risk vs. Benefit in Depression.”

First of all, Gibbons and colleagues sought to examine the benefits of certain antidepressants in order to determine whether there were differences in the response rates based on the depression severity.[2] They asked: Do patients with mild and moderate depression benefit more from antidepressants than patients with severe depression?2 To reach an answer, Gibbons and colleagues conducted a study that included the antidepressants fluoxetine and venlafaxine. Regarding fluoxetine, four youth studies of 708 patients were conducted, as well as 12 adult studies of 2,365 patients, and four geriatric studies of 960 patients.2 With venlafaxine IR (immediate release), there were 11 adult studies of 2,421 patients, and with venlafaxine ER (extended release) there were 10 adult studies of 2,461 patients.2 There were no youth or geriatric studies with venlafaxine IR or ER. Gibbons and colleagues measured youth depression using the Children’s Depression Rating Scale-Revised (CSRS-R), and they measured adult and geriatric depression using the Hamilton Depression Rating Scale (HAM-D).2 Response to antidepressants was defined as a 50 percent reduction in the CDRS-R at week six for children and a 50 percent reduction in the HAM-D at week six for adults and elderly.2

Adult and geriatric patients showed a 27.7 percent improvement with antidepressants compared with placebo, with a response rate of 58.4 percent for antidepressants and 39.9 percent for placebo.2 The severity of the depression did not affect any of the antidepressant’s efficacy, and Gibbons and colleagues state that antidepressants are beneficial for patients with mild, moderate, and sever MDD.2 Youths also showed an improvement with fluoxetine. Compared with placebo, youths taking fluoxetine showed a 29 percent greater improvement, with a response rate 29.8 percent with fluoxetine and 5.7 percent for placebo.2 The severity of MDD did not affect treatment outcome in youth, either.2

A second article by Gibbons and colleagues studied the safety of antidepressants in youth, adult, and geriatric patients with suicidal thoughts and behaviors.[3] The same groups were used as in the previous article.3 Item three on the HAM-D measured suicidal ideation and behavior in adults and elderly, and item 13 on the CDRS-R assessed such in youth.3 The question Gibbons and colleagues asked: Does depression severity mediate suicide risk?3

Youths had the highest suicide risk baseline (20 percent), followed by adults (five percent), and elderly (three percent).3 For youths treated with fluoxetine, there was a 50.3 percent decrease in suicidal thoughts and ideation.3 Adults and geriatric patients also had a significant reduction in suicidal ideation and behavior on any antidepressant: fluoxetine or venlafaxine IR or ER.3

Overall, Wagner states that Gibbons and colleagues stand for reassurance that there is efficacy and safety in using fluoxetine to treat youth, adults, and elderly MDD.1 Therefore, the next step is to analyze other antidepressants in the same way.1



[1] Wagner, K.D. (2012, August 1). Antidepressants: Risk vs. Benefit in Depression. Psychiatric Times. Retrieved from http://www.psychiatrictimes.com/child-adolescent-psych/content/article/10168/2093705.

[2] Gibbons RD, Hur K, Brown CH, et al. Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine. Arch Gen Psychiatry. 2012 Mar 5; [Epub ahead of print].

[3] Gibbons RD, Brown CH, Hur K, et al. Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. Arch Gen Psychiatry. 2012 Feb 9; [Epub ahead of print].

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