Treatment Of Depression In Children Research Articles

Serotonin and fluoxetine receptors are expressed in enamel organs and LS8 cells and modulate gene expression in LS8 cells

The selective serotonin re-uptake inhibitor (SSRI) fluoxetine is widely used in the treatment of depression in children and fertile women, but its effect on developing tissues has been sparsely investigated. The aim of this study was to investigate if enamel organs and ameloblast-derived cells express serotonin receptors that are affected by peripherally circulating serotonin or fluoxetine. Using RT-PCR and western blot analysis we found that enamel organs from 3-d-old mice and ameloblast-like cells (LS8 cells) express functional serotonin receptors, the rate-limiting enzyme in serotonin synthesis (Thp1), as well as the serotonin transporter (5HTT), indicating that enamel organs and ameloblasts are able to respond to serotonin and regulate serotonin availability. Fluoxetine and serotonin enhanced the alkaline phosphatase activity in the cell culture medium from cultured LS8 cells, whereas the expression of enamelin (Enam), amelogenin (Amel), and matrix metalloproteinase-20 (MMP-20) were all significantly down-regulated. The secretion of vascular endothelial growth factor (VEGF), monocyte chemotactic protein 1 (MCP-1), and interferon-inducible protein 10 (IP-10) was also reduced compared with controls. In conclusion, enamel organs and ameloblast-like cells express functional serotonin receptors. Reduced transcription of enamel proteins and secretion of vascular factors may indicate possible adverse effects of fluoxetine on amelogenesis.

The Dawn of Pediatric Personalized Therapeutics

Address.correspondence.to.Stephen.P..Spielberg,.MD,.PhD,. Marion.Merrell.Dow.Chair.in.Pediatric.Pharmacogenomics;. Director,.Center.for.Personalized.Medicine.and.Therapeutic. Innovation,.Children’s.Mercy.Hospital,.2401.Gillham. Road,.Kansas.City,.MO.64108,.email:.sspielberg@cmh.edu © 2010 Pediatric Pharmacy Advocacy Group It is a great honor for me to have been awarded the Sumner Yaffe Lifetime Achievement Award in Pediatric Clinical Pharmacology. Dr. Yaffe has been a lifelong mentor and colleague, a true definer of a discipline, creator of the Pediatric Pharmacology Research Units (PPRU) sponsored by the NICHD, and a dear friend. I am tremendously grateful to the PPAG for honoring me with this award in his name. The last years have been important ones for pediatric therapeutics. The scientific basis has been driven by huge advances in pediatric clinical pharmacology, fundamental understanding of the ontogeny of drug disposition and of drug response. United States legislation including the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act have changed the drug development process, leading to new knowledge about the safe, effective use of medicines in children. Research networks including the Pediatric Pharmacology Research Units (PPRUs), the Children’s Oncology Group, and now the Clinical and Translational Science Award (CTSA) network have increased pediatric investigative activities throughout the country. The National Institutes of Health (NIH) and the Food and Drug Administration (FDA) have ABBREVIATIONS ADRs,.adverse.drug. reactions;.CTSA,. Clinical. and.Translational. Science. Award;. CYP2D6,. Cytochrome.P2D6.System;.CYP2D9,.Cytochrome.P2D9. System;.EMEA,.European.Medicines.Evaluation.Agency;. FDA,.Food.and.Drug.Administration;.GENDEP,.Genome. Based.Therapeutic.Drugs. for.Depression;.GWAS,.whole. genome.association. studies;.MDD,.major. depressive. disorder;.NICHD,.National. Institute.of.Child.Health.and. Human.Development;.NIH,.National.Institutes.of.Health;. PPRU,. Pediatric. Pharmacology.Research.Units;. SSRIs,. selective.serotonin.reuptake.inhibitors. both played critical roles, with the FDA Critical Path initiative in many ways reflecting scientific thinking about translational medicine driving

The Cochrane library and the treatment of major depression in children and youth: an overview of reviews

AbstractBackgroundMajor depression (MDD) in children and adolescents is a mood disorder that has up to 25% lifetime prevalence by the end of adolescence. Pharmacological and nonpharmacological treatments are recommended to reduce symptoms, increase psychosocial functioning, and prevent relapse. Traditionally, decisions for these treatments were made based on reported effects for adults, but a body of pediatric‐based evidence is now emerging to inform treatment decisions.ObjectivesTo synthesize the evidence currently in the Cochrane Library Database of Systematic Reviews (CDSR) related to the question: ‘In children and youth with diagnosed major depression, do pharmacologic or nonpharmacologic treatments improve symptom response, response rates, functional capacity, adherence and persistence, and decrease cost and adverse events?’.MethodsCDSR was searched using the term ‘depression’ in the title for all systematic reviews examining pharmacologic and nonpharmacologic interventions for the treatment of depression in children ⩽18 years. Data were extracted and entered into tables; data were synthesized using qualitative and quantitative methods.Main ResultsOf the studies included in the CDSR, there was no significant improvement in treatment outcomes in depressed children and adolescents treated with pharmacological (tricyclic antidepressant [TCA] or selective serotonin reuptake inhibitor [SSRI]) or nonpharmacological (exercise) interventions.Author's ConclusionsAlthough this overview indicates no clear evidence for pharmacological and nonpharmacological interventions for treatment of depression in this age group, the CDSR does not include several recent research publications in this area that demonstrate beneficial effects of treatment. In context of existing research there may be a moderate effect of SSRI in moderate to severe depression in children and youth. Best practice recommendations are consideration of treatment with SSRI (fluoxetine first line) in moderate to severe depression with close monitoring and weighing risk/benefit profile based on individual assessment. Psychotherapeutic interventions not in this overview, including Cognitive Behavioral Therapy (CBT) and Interpersonal Therapy (IPT), have some evidence of effectiveness in mild to moderate depression. Although exercise remains an important part of healthy living, there is no evidence to support its use in treatment of depression in children and adolescents. This overview in the context of recent research indicates the need for ongoing study in this important area of child and youth mental health. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration

Antidepressants and suicidal ideation in adolescence: A paradoxical effect

AbstractThe past two decades have seen a rapid increase in the number and types of psychopharmacological medications that are available for the treatment of depression in children and adolescents. Parents and adolescents often raise questions as to the potential increase in suicidal ideation associated with the use of primarily selective serotonin reuptake inhibitors (SSRIs). This has been driven in part as a result of media attention that has focused on the “black box” warnings regarding increases in suicidal ideation for SSRIs. The current article reviews the status of the literature surrounding suicidal ideation and SSRIs in adolescence. Finally, the article strives to educate the clinician as to the likelihood of suicidal ideation and completions in the context of rates for all adolescents. Findings related to changes in treatment as a result of the U.S. Food and Drug Administration (FDA) black box warning are discussed as well. © 2009 Wiley Periodicals, Inc.

A critical evaluation of the role of cognitive behaviour therapy in children and adolescents with depression

AbstractDepressive disorders are relatively common in adolescents although less so in younger children. They accrue significant morbidity and frequent long-term sequelae as well as increased suicide risk in sufferers. Evidence-based treatment of depression in children and adolescents is the subject of intense investigation and debate. This article reviews the current evidence base for cognitive behaviour therapy in this group and makes recommendations for further areas of research.

Treatment with escitalopram but not desipramine decreases escape latency times in a learned helplessness model using juvenile rats

The pharmacological treatment of depression in children and adolescents is different from that of adults due to the lack of efficacy of certain antidepressants in the pediatric age group. Our current understanding of why these differences occur is very limited. To develop more effective treatments, a juvenile animal model of depression was tested to validate it as a possible model to specifically study pediatric depression. Procedures for use with juvenile rats at postnatal day (PND) 21 and 28 were adapted from the adult learned helplessness model in which, 24 h after exposure to inescapable stress, animals are unable to remove themselves from an easily escapable stressor. Rats were treated for 7 days with either the selective serotonin reuptake inhibitor escitalopram at 10 mg/kg or the tricyclic antidepressant desipramine at 3, 10, or 15 mg/kg to determine if treatment could decrease escape latency times. Escitalopram treatment was effective at decreasing escape latency times in all ages tested. Desipramine treatment did not decrease escape latency times for PND 21 rats, but did decrease times for PND 28 and adult animals. The learned helplessness model with PND 21 rats predicts the efficacy of escitalopram and the lack of efficacy of desipramine seen in the treatment of pediatric depression. These findings suggest that the use of PND 21 rats in a modified learned helplessness procedure may be a valuable model of human pediatric depression that can predict pediatric antidepressant efficacy and be used to study antidepressant mechanisms involved in pediatric depression.

Depressive disorders in children and adolescents

Depressive disorders in children and adolescents are marked by core symptoms similar to those seen in adults, although symptom expression varies greatly with developmental stage. These disorders are common, chronic, and recurrent, and they are often associated with comorbid psychiatric conditions and poor prognosis that can be alleviated by early identification and treatment. The psychiatric assessment of depressed children and adolescents can be difficult and must be performed by an expert clinician. Recent research into the treatment of depression in children and adolescents has been focused on the effectiveness of cognitive-behavioural therapy and selective serotonin reuptake inhibitors.

Perplexed trainees – what do you follow: the NICE guidelines or clinical wisdom?

We certainly agree with authors Hodes & Garralda ( Psychiatric Bulletin October 2007, 31 , 361–362) who observe that there are flaws in the National Institute for Health and Clinical Excellence (NICE) guidelines and a lack of available evidence for the treatment of depression in children and young

Juvenile rats in the forced-swim test model the human response to antidepressant treatment for pediatric depression

Currently, there are limited treatment options for major depressive disorder in children and adolescents compared to the options available for adults. Many effective treatments used for adult depression, such as the tricyclic antidepressants, lack efficacy when given to children and adolescents. To more quickly identify compounds that could be effective for treating childhood and adolescent depression, a reliable preclinical animal behavioral test of antidepressant efficacy for pediatric depression is needed. The forced-swim test (FST) with juvenile rats was assessed to determine its reliability as a predictive model for pediatric depression. We adapted procedures from the adult FST to test 21-day-old juvenile rats. The 21-day-old animals were treated with three classes of antidepressant drugs before being assessed in the FST: the selective serotonin reuptake inhibitors escitalopram or fluoxetine; the tricyclic antidepressants desipramine or imipramine; and the monoamine oxidase inhibitor tranylcypromine. The 21-day-old rats showed dose-dependent changes in behaviors similar to those seen in adults when treated with escitalopram or fluoxetine. Tranylcypromine also decreased immobility in 21-day-old rats. Treatment with desipramine or imipramine, however, was not effective at reducing immobility in the 21-day-old rats. The juvenile FST accurately predicts the efficacy of selective serotonin reuptake inhibitors and the lack of efficacy of tricyclic antidepressants in the treatment of depression in children and adolescents. This suggests that the FST using 21-day-old rats may help to develop better treatments for childhood and adolescent depression.

Improving Outcome in Pediatric Depression

Improving Outcome in Pediatric Depression

Omega-3 Treatment of Childhood Depression: A Controlled, Double-Blind Pilot Study

Omega-3 Treatment of Childhood Depression: A Controlled, Double-Blind Pilot Study

The Children's Depression Scale in Family Therapy: Hearing the Hurt

In this article I review the changes in thinking about childhood depression since the 1950s, with an emphasis on the struggles to find language for childhood depression. My interface with these changes is described, with a particular focus on the development of the Children's Depression Scale (CDS). Clinical applications of family therapy using the CDS in treatment of childhood depression are then illustrated with a composite case example. The idea is developed that depression in children can be seen as a blocked communication, and that increasing emotional expressiveness in families is an appropriate therapeutic aim and intervention. The relevance of the historical context to current practice is considered.

Randomised controlled trials of selective serotonin reuptake inhibitors in treating depression in children and adolescents: A systematic review and meta-analysis

To evaluate the efficacy of selective serotonin reuptake inhibitors (SSRIs) in children and adolescents with depressive disorder, the main electronic databases and the reference lists of retrieved articles and reviews were searched up to January 2007. Randomized controlled studies (RCT) were assessed for methodological quality, taking into consideration the specific diagnostic and severity evaluation tools used, and a meta-analysis on the efficacy of SSRIs compared placebo was undertaken. In all, 13 studies were included, covering a total of 2530 children and adolescents. Eleven studies met the criteria for inclusion in the meta-analysis. The pooled odds ratio was 1.57 (95% C.I. 1.29–1.91). Only fluoxetine appeared to offer a moderately significant benefit profile (OR = 2.39). All studies differed in diagnostic tools and primary efficacy measures. SSRI treatment, especially with fluoxetine, may be effective on child and adolescent depression. Nevertheless, additional RCTs with sound methodological designs, validated diagnostic instruments, large sample sizes, and consistent outcomes are necessary to determine the role of SSRIs, alone or in combination with psychological interventions in the treatment of depression in children and adolescents.

Abstracts

Abstracts

A Survey of Anti-Depressant Prescribing Practice and the Provision of Psychological Therapies in a South London CAMHS from 2003-2006.

A survey was conducted in a South London CAMHS before and after the publication and implementation of NICE guidelines of 2005 for the treatment of depression in children and adolescents. The results for 2006 indicate that 28% of cases were receiving medication without psychological therapy. Of those prescribed medication, 96% were receiving a prescription for fluoxetine. Of those receiving psychological therapy most received cognitive behaviour therapy whilst none received interpersonal therapy. Although 72% of cases were receiving medication with psychological therapy this falls short of the 100% expectation of the NICE guidelines. Other services are encouraged to survey young people receiving ant-depressant medication against the NICE guidelines.

Childhood depression: a place for psychotherapy

Although considered clinically effective, there is little systematic research confirming the use of Individual Psychodynamic Psychotherapy or Family Therapy as treatments for depression in children and young adolescents. A clinical trial assessed the effectiveness of these two forms of psychotherapy in treating moderate and severe depression in this age group. A randomised control trial was conducted with 72 patients aged 9-15 years allocated to one of two treatment groups. Significant reductions in disorder rates were seen for both Individual Therapy and Family Therapy. A total of 74.3% of cases were no longer clinically depressed following Individual Therapy and 75.7% of cases were no longer clinically depressed following Family Therapy. This included cases of Dysthymia and "Double Depression" (co-existing Major Depressive Disorder and Dysthymia). There was also an overall reduction in co-morbid conditions across the study. The changes in both treatment groups were persistent and there was ongoing improvement. At follow up six months after treatment had ended, 100% of cases in the Individual Therapy group, and 81% of cases in the Family Therapy group were no longer clinically depressed. This study provides evidence supporting the use of focused forms of both Individual Psychodynamic Therapy and Family Therapy for moderate to severe depression in children and young adolescents.

Effectiveness of complementary and self‐help treatments for depression in children and adolescents

To review the evidence for the effectiveness of complementary and self-help treatments for depression in children and adolescents. Systematic literature search using PubMed, PsycINFO and the Cochrane Library for 131 treatments up to February 2006. There were 13 treatments that had been evaluated in intervention studies. Studies on each treatment were reviewed by one author and checked by a second. A consensus was reached for level of evidence. Relevant evidence was available for glutamine, S-adenosylmethionine, St John's wort, vitamin C, omega-3 fatty acids, light therapy, massage, art therapy, bibliotherapy, distraction techniques, exercise, relaxation therapy and sleep deprivation. However, the evidence was limited and generally of poor quality. The only treatment with reasonable supporting evidence was light therapy for winter depression. Given that antidepressant medication is not recommended as a first line treatment for children and adolescents with mild to moderate depression, and that the effects of psychological treatments are modest, there is a pressing need to extend the range of treatments available for this age group.

Omega-3 Fatty Acids for Treatment of Childhood Depression

Omega-3 Fatty Acids for Treatment of Childhood Depression

Review of Evidence-Based Psychotherapies for Pediatric Mood and Anxiety Disorders

Aim: To review the literature on randomized clinical trials for pediatric anxiety and depression, and evaluate their quality using the criteria developed by the American Psychological Association. Method: Inclusion of randomized controlled clinical trials in the medical and psychological literature. Results: Research evidence thus far suggests that CBT is a probably efficacious treatment for depression in children. None of the CBT protocols for depressed adolescents (taken independently) meet criteria for a well-established treatment, however, if the different protocols are taken as an aggregate, then CBT meets well-established treatment criteria. In addition, IPT-A is a well-established treatment for adolescent depression. CBT is the best established treatment for a number of child and adolescent anxiety disorders. Conclusion: While there has been an increase in the number of clinical trials of psychotherapeutic interventions for depression and anxiety as well as support for empirically-based treatments, the scope of these studies is still limited and research is still needed to examine the transportability of these treatments to diverse community settings.

Duloxetine for childhood depression with pain and dissociative symptoms

Over two thirds of people suffering from depression complain of pain with or without reporting psychological symptoms. Physical symptoms are more prevalent among the women, the elderly, the poor, and in children population. Successful treatment of depression in children complicated by pain symptoms constitutes a great clinical challenge. Duloxetine has already emerged as a safe and effective treatment option for adult depressed patients with painful physical symptoms. However, no data exist in literature which suggests use of duloxetine in childhood and adolescent population for the same clinical indication. We report a case documenting successful use of duloxetine in a depressed girl child who also had severe pain and dissociative symptoms.