ReviewChildhood and adolescent depression: Why do children and adults respond differently to antidepressant drugs?
Section snippets
Adult depression
Depression describes a transient mood state experienced by virtually all individuals at some time in their life, generally in response to stressful life events as well as a serious clinical disorder. Major depressive disorder (MDD, American Psychiatric Association's DSM-IV manual) is a debilitating and serious mental illness that affects approximately 2–5% of the population worldwide, with a lifetime prevalence of around 15%. This disorder significantly interferes with the ability of the
Childhood and adolescent depression
Major depressive disorder not only affects adults but also commonly diagnosed in the pediatric population. Although the clinical symptoms of adolescent and childhood depression vary with developmental age, overall they are similar to those seen in adults. It is one of the most common mental health disorders in this population, with a prevalence in children of up to 2.5% (Birmaher et al., 1996) and during adolescence somewhere between 4 and 8%, with a 25% prevalence by the end of adolescence (
Differences between adult and juvenile animals
One approach to address this need of developing better therapies for pediatric depression is to determine the response of juvenile animals to antidepressant administration and compare to the response of adult animals. Because the brains of juvenile animals are not yet mature, it is necessary to have some understanding of the roles that maturation of the various neurotransmitter systems, particularly those for norepinephrine and serotonin, play in the response of juvenile animals to
Receptor regulation by antidepressant drugs
Because the adrenergic nervous system is not fully developed until late adolescence, the mechanisms regulating receptor density similarly may not yet be mature in young mammals, and thus the response to antidepressants that increase norepinephrine levels may be different in juveniles as compared to adults. Thus, it is of interest to compare the effects of desipramine treatment on cortical alpha-2 and beta-adrenergic receptors in juvenile and adult rats (Deupree et al., 2007). Desipramine was
Effect of desipramine administration on hypothermia
Another indication that the adrenergic nervous system is not fully developed until late adolescence is the lack of a hypothermic response of juvenile rats to acute desipramine administration. In adult rats, acute administration of desipramine results in a significant decrease in body (rectal) temperature. This effect may be a result of the increased synaptic norepinephrine activating the alpha-2A adrenergic receptor, because directly stimulating this receptor with an agonist produces
Animals models of depression and antidepressant drug action
A significant hindrance to basic research related to pediatric depression is the lack of juvenile animal models of study pediatric depression and antidepressant drug action in juveniles. Although there are some studies in which juvenile animals are subjected to various types of manipulations or stressors and then evaluated for depression-like behavior as an adult, studies on juvenile animals themselves are rare indeed. Using the two best accepted adult models, learned helplessness and the
Conclusion
Basic research directed toward the understanding of the differences in responses of juvenile and adult animals to drug administration must take into account several factors. First are the developmental aspects of the systems under study, particularly in terms of the signal transduction pathway (pharmacodynamics). Second are the difference in the pharmacokinetics, including differences in dose administered and the half-life of the agent. The antidepressant-like effects of desipramine, but not
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2021, European Journal of PharmacologyCitation Excerpt :The incidence and prevalence of adolescent depression has been rising during the last few decades (Gehlawat and Gehlawat, 2020) due to many factors, such as increasing competitive environments, higher expectations from parents and teachers, peer pressure, etc. Moreover, while there are similarities in the clinical presentation of adolescent and adult depression, there are differences in the biological correlates (Toenders et al., 2019), as well as in the responses induced by pharmacological treatments (Kaufman et al., 2001; Bylund and Reed, 2007). In this context, several studies have proven the effectiveness of different classes of antidepressant drugs when used for the treatment of depression in adults (e.g., see Charney, 1998; Cipriani et al., 2016), however, their efficacy during adolescence is controversial (see several network meta-analyses comparing the efficacy and safety of different antidepressants in children and adolescents: Cipriani et al., 2016; Boaden et al., 2020; Zhou et al., 2020; as well as several randomized controlled trials: Garland, 2004; Hetrick et al., 2007).
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2020, European NeuropsychopharmacologyCitation Excerpt :Moreover, males and females also seemed to exhibit some differences in response to certain antidepressants efficacy, although a consensus regarding these sex disparities has not been established (LeGates et al., 2019; Herzog et al., 2019). Additionally, antidepressants have been shown to differ in efficacy depending on the age of exposure, being adolescence a less responsive period than adulthood (e.g., Bylund et al., 2007; Bis-Humbert et al., 2020), during which time its use might even be harmful (Cipriani et al., 2016). In fact, all antidepressant prescriptions include a black box warning that its use in children or adolescents with depressive disorders might increase the risk of suicidal ideas and/or suicidal behaviors.