Critique: Whittington et al. – SSRIs and Adolescents

Critique of Whittington et al.’s paper Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data, written for Self-Destructive Behaviors. Citation and link to article below.


In 2004, Whittington et al. performed a meta-analysis evaluating SSRIs versus placebos on adolescents, ages 5-18 years, in the treatment of depression. Five SSRIs were evaluated: Fluoxetine, Paroxetine, Sertraline, Citalopram, and Venlafaxine. Outcome measures included remission, response to treatment, depressive symptom scores, serious adverse events, suicide-related behaviors, and discontinuing treatment due to adverse events. 165 papers were whittled down to five studies the authors report as being relevant to their investigation. It was found that all drugs, except Fluoxetine, appear to cause more harm than good.

The target population for this study is an important, but rather narrow one. Prescribing psychiatric medication to adolescents, for me, is a controversial matter. The brain is still developing, and as little as we know about the mechanism of action of these drugs, the equation becomes more complex when the chemistry of the brain is in flux. Predicting how a medication will affect a still-developing brain is difficult. As this study shows, many medications have adverse reactions in adolescents, sometimes making suicidality more likely.

It appears not much research has been done on the effects of these particular drugs on an adolescent population. This may be why the authors’ inclusion criteria allowed only five papers up for scrutiny. For this reason, all conclusions are rather suspect and require further confirmation in order for results to be generalizable. Results do shed light on the need for a risk-benefit assessment when prescribing psychiatric medications to adolescents. Medications can often be used as a band-aid in treatment. Learning coping skills and effective means of emotional regulation early in life can give a person a better chance of controlling their disorder and of remaining free of possibly harmful medications.

Fluoxetine was the only medication that showed promise for adolescents. This is important for those patients unable to reap any benefit from cognitive behavioral treatments right away due to the severity of symptoms. For these patients, treatment may be too overwhelming to engage with; safe medication would allow for a better chance of reduction of symptoms. Though, only two published studies were available for scrutiny. More information is needed on the efficacy and adverse effects of Fluoxetine.

Missing is an investigation of the incidence of completed suicide; only suicide-related behaviors were assessed. The goal of the study was to assess depression, but completed suicide is a factor of utmost importance when assessing the risks and benefits of a medication. For other types of medications death is listed as an adverse effect if data had shown it to be; it seems completed suicide is in that same vein. This is a reason Fluoxetine remains suspect, despite other positive results. It may not cause observable adverse effects, but this could be a result of reduction of reporting and increased isolation, as opposed to a reduction in depressive symptoms. If this were the case, completed suicide would be more likely and less predictable. Particularly with adolescent males, who are the most likely of the population to complete suicide. Allowing adolescents to learn the tools they need to effectively communicate their thoughts and emotions will normalize the process; hopefully allowing those who may not seek help otherwise the skills to speak up. This variable is needed to decide if Fluoxetine should be prescribed to this population.


Whittington et al_2004

  Whittington, C. J., Kendall, T., Fonagy, P., Cottrell, D., Cotgrove, A., & Boddington, E. (2004). Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. The Lancet363(9418), 1341-1345.



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