The Journal of Psychopharmacology recently published a review in which Dr Lesley Cousins and Professor Ian Goodyer discussed the impact of the antidepressant medication: selective serotonin reuptake inhibitors (SSRIs), on the developing adolescent brain.
The authors begin by reviewing what is currently understood about brain development during adolescence and how depression may affect this process. Structurally, grey matter volume follows an inverted U-shaped developmental pattern in adolescence. Conversely, white matter continues to develop across the brain and across adolescence, particularly in the frontal regions (Schmithorst and Yuan, 2010). Overall, studies have shown that adolescents with depression appear to have smaller brains than their peers (Steingard et al., 2002). In a longitudinal imaging study, reduced hippocampal growth and putamen volume (structures thought to be associated with memory and learning) were associated with the development of depression. However, the review authors highlight the difficulties of disentangling environmental factors on brain and depression development. For example, maltreatment in childhood can both hinder brain development as well as being a profound psychosocial stressor, either or both of which could trigger depression.
SSRIs are a widely used antidepressant medication and are generally considered to have fewer side effects as compared to alternatives. The authors reviewed the action of SSRIs in terms of their effects on the adolescent and adult brain. One study reviewed by the authors indicated that SSRIs increase hippocampal neurogenesis. Furthermore, another study found that a single dose of citalopram improved memory performance in healthy controls, which again suggests that this SSRI positively effects hippocampal functioning. Citalopram administration, over 7 days, was also found to reduce the response of healthy controls’ to negative emotional faces. However, the review points out that studies into the effects of SSRIs on healthy controls have not considered fluoxetine, which is the only licenced SSRI for treating adolescent depression.
Animal studies have predominantly been used to investigate the effects of fluoxetine on the adolescent brain. One such study indicated that the administration of fluoxetine stimulated cell proliferation in the hippocampus of adult rats, but not in adolescents. Furthermore, one study of rats that were treated with fluoxetine throughout adolescence found that the treatment group had long-term deficits in object recognition and spatial memory. Although these animal studies suggest that the SSRI fluoxetine could be ineffective or, at worst, detrimental to adolescent brain development the review authors advise exercising caution to such assertions. The studies are limited in that they were carried out on healthy animals; so further research with human adolescent, clinical populations is required before conclusions can be made.
Nevertheless, in 2004 the US Food and Drug Administration (FDA) advised against prescribing antidepressants to children. The guidance was based on data which suggested that taking antidepressants, including SSRIs, increased rather than mitigated under-18s’ suicidal thoughts and behaviours. However, this was based on short-term design studies, and did not include the views of suicidal patients. In contrast, the Adolescent Depression and Psychotherapy Trial (ADAPT), which actively included the views of suicidal patients, found that the propensity for depressive relapse and self-reported suicidality in adolescents were reduced with SSRI administration. Furthermore, this study found that the reduction in clinical symptoms with SSRIs appeared to be a long-term effect.
The authors conclude that there is little compelling evidence to suggest that SSRIs are detrimental to adolescent brain development. Although the concerns are not irrefutable the authors conclude that, on balance, SSRIs should continue to be prescribed to adolescents when a clinical need is identified, as the therapeutic benefits outweigh the potential developmental risks.