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Effects of Stimulants and SSRIs on Brain Function in Children: Emerging Clues from fMRI Studies.

A clinician's decision about whether or not to prescribe psychotropic medications to children has become an increasingly complex and difficult one. The clinician is faced with weighing the potential benefit of a given medication to ameliorate acute symptoms while remaining mindful of the potential long-term side effects. This decision is made even more difficult given the near absence of longitudinal studies of medication effects in children to inform these issues. Despite this, psychotropic prescriptions for the treatment of emotional and behavioral difficulties in children and adolescents have increased exponentially over the past few decades. Stimulants and antidepressants represent two of the main classes of psychotropic drugs most commonly prescribed to children (Valluri et al., 2010). 
 
Despite limited data demonstrating the efficacy and/or safety of psychotropic medications in children, a rise in pharmacotherapy has been demonstrated at progressively earlier and earlier ages [e.g., 3 years of age (Zito et al., 2000)]. This has been particularly evident in studies suggesting that the use of antidepressants for children was one of the most increasingly utilized treatments prior to the more recent “black box” warning (Valluri et al., 2010). For example, Zito and colleagues (2000) noted that prescription rates in the United States for fluoxetine increased by 1.8-fold between 1991 and 1995 in elementary and preschool age children. Similarly, Minde (1998) reported that the use of selective serotonin reuptake inhibitors (SSRIs) increased ten-fold for Canadian children 5 and younger between 1993 and 1997. Increasing rates of antidepressant use in very young children within the United States has also been found with doubling rates in preschool age (0–5 years) girls and a similarly high (64%) increase in same age boys between 1998–2002 (Delate et al., 2004). Despite declines in overall use of SSRIs after the black box warning, prescription trends have remained largely unchanged for youth diagnosed with Major Depressive Disorder (Valluri et al., 2010). 
 
Mirroring this trend, the use of stimulants in children and adolescents with attention difficulties has also notably increased over the last two decades, with 4 million children prescribed stimulants annually within the United States alone. While many children clearly benefit from their use (Connor, 2002) surprisingly little is understood about their mechanism of action and the long-term course of their early effects (Andersen, 2005; Molina et al., 2009). 
 
While the use of these medications in children has proven effective and indicated in specific clinical situations, our growing knowledge of the developing brain requires that we develop a clearer understanding of their mechanisms of action on brain systems. Based on increasing knowledge of early neuroplasticity and brain change, it has become clear that our understanding of the mechanisms of psychopharmacologic agents on brain function cannot simply be extrapolated from adults to children (Andersen & Navalta, 2011). While capturing the complex interplay between brain development and psychotropic medication use is beyond the purview of any one field of study and much less a single article, the practicing clinician may benefit from a brief review of where the field now stands in relation to this question. 
 
Recent advances in neuroimaging methodology have begun to inform this issue in adults and to a lesser degree in children. Based on this available literature, we introduce the proposed mechanisms of neural action for two of the most frequently prescribed medications in children, stimulants and SSRIs, by reviewing what is currently known about the actions of these substances in the adult brain from treatment studies using functional magnetic resonance imaging (fMRI). We also examine the few available fMRI studies of children following treatment with these medications. Possible future directions for research in this important domain are also discussed.