Childhood and adolescent depression: Why do children and adults respond differently to antidepressant drugs?

Abstract

Childhood and adolescent depression is an increasingly problematic diagnosis for young people due to a lack of effective treatments for this age group. The symptoms of adult depression can be treated effectively with multiple classes of antidepressant drugs which have been developed over the years using animal and human studies. But many of the antidepressants used to treat adult depression cannot be used for pediatric depression because of a lack of efficacy and/or side effects. The reason that children and adolescents respond differently to antidepressant treatment than adults is poorly understood. In order to better understand the etiology of pediatric depression and treatments that are effective for this age group the differences between and adults and children and adolescents needed to be elucidated. Much of the understanding of adult depression has come from studies using adult animals therefore studies using juvenile animals would likely help us to better understand childhood and adolescent depression. Recent studies have shown both neurochemical and behavioral differences between adult and juvenile animals after antidepressant treatment. Juvenile animals have differences compared to adult animals in the maturation of the serotonergic and noradrenergic systems, and in dose of antidepressant drug needed to achieve similar brain levels. Differences after administration of antidepressant drug have also been reported for adrenergic receptor regulation, a physiologic hypothermic response, as well as behavioral differences in two animal models of depression. The differences between adults and juveniles not only in the human response to antidepressants but also with animals studies warrant a specific distinction between the study of pediatric and adult depression and the manner in which new treatments are pursued.

Evidence-Based Treatments in Treatment-Naïve and Treatment-Resistant Pediatric Obsessive-Compulsive Disorder

“…The effect seems to be greater in patients with comorbid OCD and tic disorder [61]. However, no RCT exists in pediatric OCD, and inferring that children and adolescents should benefit in the same way as adults are fraught with difficulties and depend on the presupposition that adult and pediatric OCD are equivalent, even though the transmitter systems in young people are not mature as those in adults [62]. However, naturalistic open trials using risperidone and aripiprazole as an augmentation to an SSRI in pediatric OCD indicate that the combination may be beneficial [44,63,64].…”

Ontogeny of Norepinephrine Transporter Expression and Antidepressant-Like Response to Desipramine in Wild-Type and Serotonin Transporter Mutant Mice

“…This problem is compounded in juveniles and adolescents, because there are fewer pharmacological treatment options for these patients compared with adults (Bylund and Reed, 2007). The U.S. Food and Drug Administration approved two antidepressant drugs, fluoxetine and escitalopram, for use in treating pediatric depression.…”

“…The ensuing increase in extracellular norepinephrine (NE) and 5-HT is thought to trigger therapeutic downstream events (Frazer, 1997). It has been suggested that a developmental delay in the noradrenergic central nervous system may limit the antidepressant potential of NET-targeting TCAs in juveniles and adolescents compared with adults (Bylund and Reed, 2007). However, other reports go against this idea.…”

Iatrogenic Comorbidity in Childhood and Adolescence: New Insights from the Use of Antidepressant Drugs

“…Adverse events primarily include altered growth velocity, rash, dystonia, tics, affect lability, activation, metabolic blood test abnormalities, sedation, sialorrhea, and electrocardiogram irregularities [3]. Variations in terms of treatment response may be ascribed to the incomplete development of the central nervous system [4]. In particular, a major role has been attributed to the immature adrenergic system in characterizing response to psychotropic drugs in children and young adolescents [4].…”

“…Variations in terms of treatment response may be ascribed to the incomplete development of the central nervous system [4]. In particular, a major role has been attributed to the immature adrenergic system in characterizing response to psychotropic drugs in children and young adolescents [4]. Unfortunately, there is little consensus as to the assessment of adverse events in children and adolescents.…”