Depression in children and adolescents

Merry S, McDowell H, Hetrick S, Bir J, Muller N. Psychological and/or educational interventions for the prevention of depression in children and adolescents. Cochrane Database Syst Rev 2004. 

Ryan, N., and Dahl, R. (1993) The biology of depression in children and adolescents. In Mann, J. and Kupfer, D., eds. The Biology of Depressive Disorders. New York Plenum Press, pp. 37-58. 

If at the end of the continuation phase it is decided that the antidepressants should be discontinued, this should be done gradually (e.g., over 6 weeks) to avoid withdrawal effects such as sleep disturbance, irritability, or gastrointestinal symptoms, which may lead the clinician to misinterpret the need for continued medication treatment. Clinical practice has suggested that rapid discontinuation of antidepressants may precipitate a relapse or recurrence of depression. In children and adolescents, it is recommended that treatment be discontinued while they are on extended vacations, rather than during the school year. 

Emslie, G.J., Heiligenstein, J.H., Hoog, S.L., Judge, R., Brown E.B., and Nilsson, M. (2000) Fluoxetine for acute treatment of depression in children and adolescents a placebo controlled randomized clinical trial. Presented at the 39th Annual Meeting of the American College of Neuropsychopharmacology, San Juan, Puerto Rico. 

Finch, A.J., Lipovsky, J.A., and Casat, C.D. (1989) Anxiety and depression in children and adolescents negative affectivity or separate constructs In Kendall, P.C. and Watson, D. eds. Anxiety and Depression Distinctive and Overlapping Features. San Diego Academic Press, pp. 171-196. 

Ryan ND, Dahl RE The biology of depression in children and adolescents, in Biology of Depressive Disorders, Part B Subtypes of Depression and Gomorbid Disorders. Edited by Mann JJ, Kupfer D. New York, Plenum, 1994 Rybakowski J, Erazer A, Mendels J Lithium efflux from erythrocytes incubated in vitro during lithium carbonate administration. Communications in Psychopharmacology 2 105-112, 1978... 

Thus, the upper limit to the therapeutic range is a function of toxicity rather than reduced efficacy in contrast to the other TCAs. Perry et al. ( 326) proposed a minimal threshold for this tertiary amine TCA of 265 ng/mL (imipramine plus desimipramine) with a remission rate of 42% above this threshold versus 15% below it. Of note, this threshold for optimal antidepressant response is closer to the threshold for CNS and cardiac toxicity than for any other TCA. Preskorn and colleagues ( 327) found a lower optimal threshold for imipramine plus desimipramine (125 ng/mL) when it was used to treat clinical depression in children and adolescents than when used in adults. 

Despite the diagnostic challenges that remain in trying to understand the nature of MDD in children and adolescents, advances in its treatment has progressed considerably since the last edition of this textbook. Over this interval, selective serotonin reuptake inhibitors (SSRIs) have superseded TCAs as the treatment of first choice based both on efficacy and safety considerations. As in adults, specific psychotherapies (cognitive therapy, cognitive-behavioral therapy, and interpersonal therapy) may be as effective as antidepressant medication, at least in mild to moderate depression in children and adolescents ( 111, 112). Also, evidence indicates that depression in children and adolescents may be more influenced than is depression in adults by psychosocial variables such as peers and family, as well as other environmental factors (113). 

From 1996 to 1997, 792,000 prescriptions for SSRIs were written to treat depression in children and adolescents between 6 and 18 years of age, primarily because of the safety of these medications compared with TCAs and because of growing evidence of their efficacy (116, 117). 

Besides biasing the results, companies have also suppressed unfavorable research. GlaxoSmithKline did not publish results that showed that paroxetine (Paxil ) was ineffective for the treatment of depression in children and adolescents because, according to an internal company memo, "It would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine" (Kondro and Sibbald 2004 783). The Wall Street foumal claims that "internal Merck e-mails and marketing materials as well as interviews with outside scientists show that the company fought forcefully for years to keep safety concerns from destroying the drug s [Vioxx s] commercial prospects" (Mathews and Martinez 2004 Al). 

Preliminary evidence suggests efficacy for other anxiety disorders and depression in children and adolescents... 

Phoplys S. Depression in children and adolescents with epilepsy. Epilepsy Behav 2003 4 S39-A5. 

Emslie GJ, Rush AJ, Weinberg WA et al. A double-blind, randomized, placebo-controUed trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 1997 54 1031-7 Hazell P, O Connell D, Heathcote D, Henry D. Tricyclic drugs for depression in children and adolescents. (Cochrane Review). In The Cochrane Library, Issue 1,2004. 

HANDBOOK OF DEPRESSION IN CHILDREN AND ADOLESCENTS Edited by William M. Reynolds and Hugh F. Johnson... 

Data supporting efficacy of antidepressants in children and adolescents are sparse. Fluoxetine is the only antidepressant that is FDA approved for treatment of depression in patients less than 18 years of age. 

The dopamine transporter has been a target for developing pharmacotherapies for a number of CNS disorders including ADHD, stimulant abuse, depression and Parkinson s disease. Several excellent reviews in this area have been recently published [28-30]. The dopamine reuptake inhibitor methylphenidate has been successfully used for decades in the management of ADHD in children and adolescents. It remains a first-line treatment along with amphetamine for this disorder [31,32]. 

Suicidaiity in chiidren and adoiescents Antidepressants increased the risk of suicidal thinking and behavior (suicidaiity) in short-term studies in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone... 

Suicidality in children and adolescents Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of trazodone or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Trazodone not approved for use in pediatric patients (see Clinical worsening and suicide risk and Children sections in Warnings). 

In this chapter we review extant data on the neurobiology of unipolar and bipolar depressive disorders in children and adolescents. A complement to two recent reviews (Kaufman and Ryan, 1999 Kaufman et ah, 2001), this chapter places primary emphasis on those studies in which neuroimaging techniques have been used. Unfortunately, such studies are few and far between. Preclinical models that have guided research on the neurobiology of affective disorders in adults are discussed, and, given the limits in the application of these models to juvenile samples, especially in the case of unipolar disorder, the need for more developmentally focused preclinical work is emphasized. 

Limitations in the Application of Preclinical Models of Effects of Stress in Organizing Neurobiological Correlates of Major Depressive Disorder in Children and Adolescents... 

To the best of our knowledge, no studies with child and adolescent depressed cohorts have examined hippocampal volume. The one study that examined hippocampal volume in children and adolescents with PTSD (n = 43), about half of whom met criteria for comorbid MDD, failed to find evidence of hippocampal atrophy (De Beilis et ah, 1999). This finding is not surprising, as most of the children and adolescents in the study had not experienced more than one episode of depression, and hippocampal atrophy was found to be correlated with total lifetime duration of illness in the prior adult studies cited (Sheline et ah, 1996 Brem-ner et ah, 2000). Developmental factors may also account for the discrepant findings in child and adult studies. For example, age-dependent changes in sensitivity to some forms of N-methyl-D-aspartate (NMDA) receptor blockade neurotoxicity in corticolimbic regions have been reported in preclinical studies, with cell death minimal or absent prepuberty and reaching peak in early adulthood (Father et ah, 1995). 

Preliminary Results of Neuroimaging Studies in Children and Adolescents with Depression... 

Unipolar and bipolar depressive disorders in children and adolescents are serious conditions. The pathophysiology of these disorders is poorly understood. The new tools available through neuroimaging techniques will help to unravel the neuroanatomical systems involved in the onset and recurrence of these disorders. There is a need for more developmentally informed predinical research and more studies of the normal development of the neural systems implicated in emotional regulation. 

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