Prozac May Not Increase Suicide Ideation in Children

I saw an interesting item in AMA MorningRounds about Fluoxetine (Prozac) and the risk of suicide thinking in children and adolescents. In 2004, the FDA issued a Black Box Warning about the possibility of increased risk for suicidality in this age group. And in 2006, the Black Box Warning was extended to those up to age 25.

A recently published review challenged the notion that antidepressants increase suicidality in young people. The study was in the Archives of General Psychiatry and examined data from 41 clinical trials involving over 9,000 adults and children [1]. The children were taking Prozac and the adults were taking either Prozac or Venlafaxine (Effexor). The bottom line is that taking antidepressants was associated with reduced risk of suicidal thoughts and behavior in adult and there was no effect of antidepressant either up or down with suicidality in kids.

The mediating effect of suicidality reduction in adults seemed to be a reduction in the severity of  depression, which makes sense. However, while depression in youths responded to antidepressant, there was not a corresponding reduction in suicide ideation, although antidepressant itself was not associated with that. The authors speculated that other psychopathology might explain the persisting suicidality.

1. Gibbons, R. D., C. H. Brown, et al. (2012). “Suicidal Thoughts and Behavior With Antidepressant Treatment: Reanalysis of the Randomized Placebo-Controlled Studies of Fluoxetine and Venlafaxine.” Arch Gen Psychiatry: archgenpsychiatry.2011.2048.
Context The US Food and Drug Administration issued a black box warning for antidepressants and suicidal thoughts and behavior in children and young adults. Objective To determine the short-term safety of antidepressants by standard assessments of suicidal thoughts and behavior in youth, adult, and geriatric populations and the mediating effect of changes in depressive symptoms. Data Sources All intent-to-treat person-level longitudinal data of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride. Study Selection All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine. Data Extraction The suicide items from the Children’s Depression Rating Scale-Revised and the Hamilton Depression Rating Scale as well as adverse event reports of suicide attempts and suicide during active treatment were analyzed in 9185 patients (fluoxetine: 2635 adults, 960 geriatric patients, 708 youths; venlafaxine: 2421 adults with immediate-release venlafaxine and 2461 adults with extended-release venlafaxine) for a total of 53 260 person-week observations. Data Synthesis Suicidal thoughts and behavior decreased over time for adult and geriatric patients randomized to fluoxetine or venlafaxine compared with placebo, but no differences were found for youths. In adults, reduction in suicide ideation and attempts occurred through a reduction in depressive symptoms. In all age groups, severity of depression improved with medication and was significantly related to suicide ideation or behavior. Conclusions Fluoxetine and venlafaxine decreased suicidal thoughts and behavior for adult and geriatric patients. This protective effect is mediated by decreases in depressive symptoms with treatment. For youths, no significant effects of treatment on suicidal thoughts and behavior were found, although depression responded to treatment. No evidence of increased suicide risk was observed in youths receiving active medication. To our knowledge, this is the first research synthesis of suicidal thoughts and behavior in depressed patients treated with antidepressants that examined the mediating role of depressive symptoms using complete longitudinal person-level data from a large set of published and unpublished studies.