抗抑郁药物治疗儿童青少年抑郁症的临床试验进展

本文目的是归纳并总结新型抗抑郁药物治疗儿童青少年抑郁症的效果和安全性,为儿童青少年抑郁症的药物干预提供参考。抑郁症是儿童青少年常见的精神疾病之一,严重影响患者的健康成长,可造成自杀等严重不良后果。使用抗抑郁药物是治疗儿童青少年抑郁症的重要手段,然而可用于儿童青少年的抗抑郁药物种类较少,临床应用受到一定限制。本文就近十年抗抑郁药物治疗儿童青少年抑郁症的临床试验进展进行综述。     

Treatment and Prevention of Depression and Anxiety in Youth: Test of Cross-Over Effects

Anxiety and depression are highly comorbid and share several common etiological processes. Therefore, it may be more efficient to develop interventions that treat or prevent these problems together rather than as separate entities. The present meta-analytic review examined whether interventions for children and adolescents that explicitly targeted either anxiety or depression showed treatment specificity or also impacted the other outcome (i.e. cross-over effects). We addressed this question both within the same type of study (i.e. treatment, prevention) and across study types. Only randomized controlled trials (RCTs) that assessed both constructs with dimensional measures were included in this review. For treatment studies, RCTs targeting anxiety (n = 18) showed significant effects on both anxious and depressive symptoms, although more strongly on anxiety than depression; similarly, RCTs treating depression (n = 9) yielded significant effects on both depressive and anxious symptoms, but stronger effects on depression than anxiety. Thus, there were cross-over effects in treatments purportedly targeting either anxiety or depression, and also treatment specificity, such that larger effects were seen for the target problem at which the treatment was aimed. Anxiety prevention studies (n = 14) significantly affected anxious, but not depressive symptoms, indicating no cross-over effect of anxiety prevention trials on depression. For depression prevention studies (n = 15), the effects were not significant for either depressive or anxiety symptoms, although the effect was significantly larger for depressive than for anxious symptoms. Post-hoc analyses revealed that the effect on depressive symptoms was significant in depression preventions trials of targeted but not universal samples. Implications for transdiagnostic interventions are discussed.     

Posttraumatic Stress Disorder in Children and Adolescents: A Review of Psychopharmacological Treatment

PTSD in children and adolescents differs from the adult disease. Therapeutic approaches involve both psychotherapy and psychopharmacotherapy. Objectives: The current paper aims at reviewing studies on psychopharmacological treatment of childhood and adolescent PTSD. Additionally, developmental frameworks for PTSD diagnosis and research along with an experimental model of quenching and kindling in the context of stress exposure are presented. We conducted an extensive literature search of reviews on psychopharmacotherapy as well as studies on psychopharmacological treatment for PTSD among children and adolescents. We used the database PubMed and focused on the time period of the last 10 years up to January 2009. Pertinent earlier papers were also included.There are a limited number of studies specifically assessing the psychopharmacological treatment of PTSD in children and adolescents. The vast majority of them lack verification in RCTs. Only the use of imipramine, divalproex sodium and sertraline were already evaluated in RCTs. Future studies should take into account developmental approaches to the diagnosis and treatment of PTSD in children and adolescents. In this context, different underlying neurobiological patterns, which are reflected in distinct clinical symptomatology, require a precise investigation and a symptom-orientated psychopharmacological approach.     

Efficacy of antidepressants in juvenile depression: meta-analysis

BACKGROUND: The safety of antidepressants in children and adolescents is being questioned and the efficacy of these drugs in juvenile depression remains uncertain. AIMS: To assess antidepressant efficacy in juvenile depression. METHOD: Systematic review and meta-analysis of randomised controlled trials (RCTs) comparing responses to antidepressants, overall and by type, v. placebo in young people with depression. RESULTS: Thirty drug-placebo contrasts in RCTs lasting 8 weeks (median) involved 3069 participants (512 person-years) of average age 13.5 years. Meta-analysis yielded a modest pooled drug/placebo response rate ratio (RR=1.22, 95% CI 1.15-1.31), with little separation between antidepressant types. Findings were similar for response rate differences and corresponding number needed to treat (NNT): overall NNT=9; tricyclic antidepressants NNT=14 > serotonin reuptake inhibitors NNT=9 > other antidepressants NNT=8. Numbers needed to treat decreased with increasing age: children (NNT=21) > mixed ages (NNT=10) > adolescents (NNT=8). CONCLUSIONS: Antidepressants of all types showed limited efficacy in juvenile depression, but fluoxetine might be more effective, especially in adolescents. Studies in children and in severely depressed, hospitalised or suicidal juvenile patients are needed, and effective, safe and readily accessible treatments for juvenile depression are urgently required.     

Major depressive disorder in adolescence: a brief review of the recent treatment literature.

OBJECTIVE: Treating adolescents with depression remains a major clinical and public health challenge. Because of the serious morbidity and mortality associated with adolescent major depressive disorder (MDD), there is a need to review the published literature on treatment efficacy to establish effective treatment choices for these adolescents. METHOD: We reviewed the recent literature on the treatment of MDD in adolescents using the Medline and PsycINFO computerized databases. RESULTS: Results of open studies of MDD treatment in adolescents suggested therapeutic efficacy; however, later, better-controlled studies are more difficult to interpret, owing to the high rate of improvement with placebo. Currently, there is limited evidence of robust, effective therapeutic interventions in children and in adolescent depressive disorders. CONCLUSIONS: Despite limitations, current findings from studies investigating selective serotonin reuptake inhibitors (SSRIs), cognitive-behavioural therapy, and interpersonal therapy generally support these treatments as safe and effective for adolescent MDD. Still, further investigations into these treatments for adolescent depression are warranted.     

Refractory depression in children and adolescents

Refractory or treatments resistant depression in child and adolescent populations is a difficult construct to operationalize currently. To date, only one of the small number of completed double-blind placebo-controlled treatment investigations have not demonstrated a significant effect of antidepressants in comparison to placebo. However, it has been established that child and adolescent MDD is a serious disorder that appears to have clinical continuity with adult affective disorders and is generally of long duration with high rates of recurrence and eventual progression to mania, substance abuse, or other serious psychopathology. In addition, families of children with affective disorders evidence substantial genetic loading with high rates of affective disorders contributing both genetic vulnerability and potential environmental risk as well. There have been no empirically identified treatments that alter the long-term course of the illness. Thus treatment resistance is a significant issue for this population. This review will focus on controlled treatment trials and will examine the potential relevance of psychosocial impairment, genetic-familial risk, and neuromorphometric brain differences to treatment resistance in children and adolescents with major depression. Depression and Anxiety 5:212–223, 1997. © 1997 Wiley-Liss, Inc.     

Selective serotonin re-uptake inhibitors for children and adolescents

Objectives: 1) To briefly review the scientific basis for the use of selective serotonin re-uptake inhibitors (SSRIs) in children and adolescents. 2) To review the current data on the efficacy, safety and tolerability in children and adolescents. Method: A Medline search back to 1990 was conducted. Review articles and double blind, placebo controlled trials were critically reviewed. Additional hand searches were performed with key journals and in specific areas of interest for this paper. Results: Most of the published papers are from North America. There is an increasing use of SSRIs in child and adolescent psychiatry. The main disorders studied are mood and anxiety disorders. The data supporting efficacy is still limited. The most robust data is the treatment of OCD and depression. Conclusion: Taking the limited data together with clinical experience and with adult studies, there is a valuable role for SSRIs as a component of treatment for various child and adolescent psychiatric disorders.

     

Depression in children and adolescents: Does gender make a difference?

The occurrence of depression is higher in females after puberty, suggesting a gender-related difference. This article reviews studies that have examined gender differences in the presentation and treatment of depression in adults and discusses how this information applies to depressed children and adolescents. The adult literature suggests that men and women vary in presentation of depression. In addition, differences exist in the pharmacokinetic properties of various medications, but it is unclear how they affect clinical treatment response. Studies of gender differences in child and adolescent depression are limited. Some studies suggest that differences seen in adults may also apply to children and adolescents. Studies of gender differences in treatment response are not available, however. Further study and evidence-based exploration are required to better understand gender differences in depression in children and adolescents.     

Associations between adolescent depression and parental mental health, before and after treatment of adolescent depression

The negative impacts of parental mental health problems on children and adolescents are well known, but the relationship between a child’s depression and their parents’ health is not so well understood. Being a carer/parent of someone with mental illness can be associated with negative outcomes for the caregiver. This paper reports the associations between the mental health of adolescents with major depression and their parents, before and after treatment of the adolescent’s depression. Data were collected as part of the Adolescent Depression Antidepressants and Psychotherapy Trial, a randomised controlled trial of selective serotonin reuptake inhibitors with and without cognitive behaviour therapy in 208 clinic-recruited adolescents with major depression. The baseline severity of depression in the adolescent was significantly associated with both maternal and paternal mental health (as rated by the General Health Questionnaire). This effect was not confounded by other psychiatric symptoms. The degree of improvement in parental and child mental health was positively correlated across time. Our results support the hypothesis that there is a significant association between parental mental health and adolescent depressive symptoms. This study was not able to establish the direction of this association. In clinical practice, the findings demonstrate the importance of considering the mental health of the parents when treating depressed adolescents.     

Cognitive-behavioral therapy for adolescent depression: a meta-analytic investigation of changes in effect-size estimates

OBJECTIVE: To explicate differences between early and recent meta-analytic estimates of the effects of cognitive-behavioral therapy (CBT) for adolescent depression. METHOD: Meta-analytic procedures were used to investigate whether methodological characteristics moderated mean effect sizes among 11 randomized, controlled trials of CBT focusing on adolescents meeting diagnostic criteria for unipolar depression. RESULTS: Cumulative meta-analyses indicated that effects of CBT have decreased from large effects in early trials, and confidence intervals have become narrower. Effect sizes were significantly smaller among studies that used intent-to-treat analytic strategies, compared CBT to active treatments, were conducted in clinical settings, and featured greater methodological rigor based on CONSORT (Consolidated Standards of Reporting Trials) criteria. The mean posttreatment effect size of 0.53 was statistically significant. CONCLUSIONS: Differences in estimates of the efficacy of CBT for depressed adolescents may stem from methodological differences between early and more recent investigations. Overall, results support the effectiveness of CBT for the treatment of adolescent depression.     

The selective serotonin reuptake inhibitors controversy in the treatment of depression in children

Antidepressants are widely prescribed for children and adolescents, although data regarding their safety and efficacy are limited. The objective of this article is to review the origins of the controversy regarding the current use of selective serotonin reuptake inhibitors (SSRIs) in children and adolescents. Two chief concerns drive the controversy: 1) the discovery of an increased risk of suicidal behaviors in those treated with SSRIs and 2) the efficacy of SSRIs in childhood and adolescent major depression is unclear. Various factors may account for the reported differences in outcomes for SSRI treatment in children and adolescents compared to adults. The past decade has shown a significant drop in the rate of adolescent suicide, which coincides with the onset of the use of these medications. Therefore, a reduction in the use of SSRIs in children and adolescents should be considered carefully.     

Pharmacological treatment of adolescent major depression

Antidepressant agents are widely prescribed for adolescents, although specific data regarding their efficacy in this age range are limited. The aims of the present article are to review research findings regarding the use of antidepressant drugs for adolescent depression and to discuss the main results in light of our clinical experience. Only 13 controlled trials on the use of antidepressant drugs for adolescent major depression are available in the literature. Six studies evaluated the efficacy of tricyclic antidepressants, yet they only included 196 adolescents altogether. Seven studies, including a total of 1,403 patients, evaluated the efficacy of three specific serotonin reuptake inhibitors: fluoxetine, paroxetine, and sertraline. Based on published data, serotonin reuptake inhibitors appear to be the first-line psychopharmacologic treatment for adolescent depression, as three compounds (fluoxetine, paroxetine, and sertraline) appeared to be effective in this indication. Conversely, all published studies failed to demonstrate that the tricyclic antidepressants were superior to placebo. Several questions remain open and are discussed: How should we use available scientific data in clinical practice? Are there nonspecific factors implicated in treatment response? Is there a serotonin hypothesis for juvenile depression? What are the priorities for future research?     

Applications of transcranial magnetic stimulation (TMS) in child and adolescent psychiatry

Transcranial magnetic stimulation (TMS) is emerging as a new treatment and neurophysiological research tool for psychiatric disorders. Recent publications suggest that this modality will also serve as a treatment and research tool in child and adolescent psychiatry. Current reports on therapeutic trials of repetitive transcranial magnetic stimulation (rTMS) in adolescents have primarily focused on depression. However, other pilot work involves the treatment of attention-deficit/hyperactivity disorder (ADHD), autism and schizophrenia. Neurophysiological studies typically utilize single and paired-pulse TMS paradigms which index cortical excitability and inhibition. Initial studies have focused on ADHD, autism, and depression. General knowledge regarding TMS among child and adolescent psychiatrists is lacking. The aim of this review is to provide an overview of TMS in the context of child and adolescent psychiatry, discuss recent therapeutic and neurophysiological studies, and examine relevant ethical considerations.     

A systematic review of treatment of typical absence seizures in children and adolescents with ethosuximide, sodium valproate or lamotrigine.

PURPOSE:To evaluate the role of ethosuximide, sodium valproate and lamotrigine in children and adolescents with typical absence seizures (AS). METHODS: A systematic review of randomized controlled trials that included children or adolescents with typical absence seizures who received treatment with ethosuximide, sodium valproate or lamotrigine. RESULTS: Four RCTs fulfilled the inclusion criteria. Due to the heterogeneity of the studies the results could not be pooled in a meta-analysis. CONCLUSIONS: We found no reliable evidence to inform clinical practice. The design of further trials should be pragmatic and compare one drug with another.     

The contribution of pharmacoepidemiology to the antidepressant-suicidality debate in children and adolescents

A number of concerns have recently been raised about whether or not antidepressant medications are associated with suicidal thoughts and behaviour in children and adolescents. These concerns are based largely on results of meta-analyses of randomized, controlled trials (RCTs). Controversy exists about generalizing evidence from short-term RCTs, designed primarily to test efficacy outcomes, to routine practice settings. Pharmacoepidemiological studies complement RCTs by using observational methods to examine safety and effectiveness of medications in the general population. This article reviews the contribution of pharmacoepidemiology to the controversy surrounding suicide risk in children and adolescents taking antidepressants, noting how variations in study design and adjustment for potential confounding factors influence outcome.     

The contribution of pharmacoepidemiology to the antidepressant-suicidality debate in children and adolescents

A number of concerns have recently been raised about whether or not antidepressant medications are associated with suicidal thoughts and behaviour in children and adolescents. These concerns are based largely on results of meta-analyses of randomized, controlled trials (RCTs). Controversy exists about generalizing evidence from short-term RCTs, designed primarily to test efficacy outcomes, to routine practice settings. Pharmacoepidemiological studies complement RCTs by using observational methods to examine safety and effectiveness of medications in the general population. This article reviews the contribution of pharmacoepidemiology to the controversy surrounding suicide risk in children and adolescents taking antidepressants, noting how variations in study design and adjustment for potential confounding factors influence outcome.     

Epidemiology of childhood depressive disorders: a critical review

The methodology of 14 recent epidemiological studies of childhood and adolescent depressive disorders was critically reviewed and findings summarized for prevalence, comorbidity, correlates, risk factors, and outcome. Shortcomings in sampling and considerable inconsistency in the measurement of depression in the studies made it difficult to draw firm conclusions about the prevalence and correlates of depression in young people. Nonetheless, it is likely that major depressive disorder is relatively uncommon in prepubertal children, increases in frequency in adolescents, and is significantly associated with such variables as family dysfunction and low self-esteem. Comorbidity of depression with other psychiatric disorders was also high in these nonpatient samples and it will be important in future work to assess the implications of this for the etiology, treatment, and prognosis of depressive disorders in children and adolescents.     

Ultradian rhythms and temporal coherence in sleep EEG in depressed children and adolescents.

BACKGROUND: It has been suggested that a primary ultradian (80-120 minute) rhythm disturbance in EEG underlies sleep abnormalities in adults with depression. The present study evaluated ultradian rhythm disturbances in childhood and adolescent depression. METHODS: Sleep macroarchitecture and temporal coherence in quantitative EEG rhythms were investigated in 50 medication-free outpatients with major depression (25 children and 25 adolescents) and 15 healthy normal controls (5 children and 10 adolescents). RESULTS: Few of the macroarchitectural measures showed significant group effects. In fact, age and sex effects were stronger than disease-dependent components. Temporal coherence of EEG rhythms during sleep did differentiate those with MDD from controls. Both depressed children and adolescents had lower intrahemispheric coherence, whereas interhemispheric was only lower in depressed adolescents in comparison with controls. Gender differences were evident in adolescents, but not children, with MDD with lowest interhemispheric coherence in adolescent girls. CONCLUSIONS: These findings are in keeping with increased risk for depression in females beginning at adolescence and extending throughout adulthood. It was suggested that low temporal coherence in depression reflects a disruption in the fundamental basic rest-activity cycle of arousal and organization in the brain that is strongly influenced by gender.     

Effects of Internet-Based Acceptance and Commitment Therapy (IACT) on Adolescents: A Systematic Review and Meta-Analysis

Objectives: This study reviewed published randomized controlled trials (RCTs) and evaluated the efficacy of internet-based acceptance and commitment therapy (IACT) on adolescent mental health. Methods: Searches were conducted in PubMed, ProQuest, APA (PsycNET/PsycINFO), and Web of Science from inception to January 2022 to identify RCTs evaluating the effects of IACT on adolescents. The included studies were assessed for quality and risk of bias. This study was performed using the standard mean difference and associated 95% confidence interval of effective measures. Review Manager 5.4 software was adopted to calculate the effect size. Results: Compared to adolescents in control groups, those in the IACT groups showed some improvement in the efficacy of depression symptoms (SMD = −0.24, 95% CI = [−0.44, −0.05], p = 0.01) and had a small but significant effect on reducing experiential avoidance (SMD = −0.24, 95% CI = [−0.46, −0.01], p = 0.04). However, the effect size on anxiety did not reach the threshold (SMD = −0.18, 95% CI = [−0.27, −0.09], p < 0.0001). In addition, there were no significant differences in stress and well-being compared to those of the control group. Compared with universal adolescents, IACT was found to have a more significant therapeutic effect on targeted adolescents. Conclusions: IACT is effective in adolescent mental health interventions, but its clinical reliability and significant efficacy are limited, and more rigorous RCTs are needed in future studies.