Antidepressants and Adolescent Brain Development

Emily Karanges; Iain S McGregor


Future Neurology. 2011;6(6):783-808. 

In This Article

Abstract and Introduction


Despite being a first-line treatment for adolescent depression and anxiety, antidepressant drugs appear to have questionable efficacy and carry an increased risk of adverse effects in this population. The neural mechanisms underlying this phenomenon are currently unknown. Recent research into the neural effects of alcohol and recreational drugs suggests that the developmental trajectory of the adolescent brain may be particularly vulnerable to pharmacological disturbance. It is therefore important to consider whether prescription psychotropic drugs may have analogous effects. This article reviews the contribution of recent preclinical, clinical and pharmacogenetic literature to current knowledge on the short-term and enduring neural effects of antidepressants on the adolescent brain, with a particular focus on the major neurotransmitter systems and neuroplasticity.


The idea that the developing brain is a highly malleable structure that is particularly vulnerable to environmental toxins has long been recognized. Both the preclinical and human literature has repeatedly demonstrated that prenatal and early life exposure to a variety of drugs can have untoward and lasting consequences on brain development (see [1–3] for reviews). Examples include methamphetamine-induced disturbances in dopaminergic regions[4] and the widespread structural and functional abnormalities apparent in individuals with fetal alcohol spectrum disorders.[5] The last decade has brought increasing recognition that this period of vulnerability is not limited to early life. Instead, the brain continues to undergo extensive reorganization and growth during childhood and adolescence and into early adulthood, rendering it susceptible to environmental influences throughout these periods. While much of the literature has focused on the characteristics of the adolescent brain in terms of vulnerability to addiction and susceptibility to the toxicity of alcohol, nicotine and illicit drugs,[6–12] there is increasing recognition that the susceptibility of this period also extends to the effects of psychotropic drugs, including antidepressants, stimulants and antipsychotics.[13–15] Children and adolescents are not little adults, and often display different behavioral and neural responses to pharmacological manipulations.

However, there is debate on whether the malleability of the brain during adolescence is a window of opportunity in which treatment might allow greater potential for adaptive recovery or whether exposure to psychotropic medications may have enduring negative effects.[14] Given the recent increases in the prescription of psychotropic drugs to children and adolescents[16] and the explosion in the diagnosis of psychiatric disorders in this population,[17,18] a detailed knowledge of the immediate and long-term effects of such drug treatment is vital to informing clinical practice. In this article, we review and discuss the current knowledge on both the immediate and long-term neural effects of antidepressant treatment during late childhood and early adolescence.


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