Is the medication bottle for pediatric and adolescent depression half-full or half-empty?
2005; Elsevier BV; Volume: 37; Issue: 6 Linguagem: Inglês
10.1016/j.jadohealth.2005.09.009
ISSN1879-1972
Autores Tópico(s)Digital Mental Health Interventions
ResumoMa and colleagues, in this issue of the Journal of Adolescent Health, have done an excellent job of capturing major trends in the treatment of adolescent depression in the United States from 1995 through 2001 [[1]Ma J. Lee K.-V. Stafford R.S. Depression treatment during outpatient visits by U.S. children and adolescents.J Adolesc Health. 2005; 37: 434-442Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar]. The authors note with alarm an increase in the off-label use of antidepressants and a decline in the use of psychotherapy. Are the changes reported really bad news, or are the conclusions of the authors unduly pessimistic? As someone who has focused on the use of cognitive behavior therapy for the treatment of depression, perhaps I can apply my clinical skills to help provide some room for optimism. It has been well established that pediatric and adolescent emotional and behavioral disorders are under-recognized and under-treated. Therefore, the increase in the number of visits of children and adolescents should be viewed favorably, because this implies that parents and physicians are doing a better job of recognizing and diagnosing depression. The adolescent suicide rate had been climbing steadily from the 1950s until close to 1990, when it first stabilized, and then began declining in the early 1990s. Although it is impossible to prove, it seems likely that improved recognition, diagnosis, and treatment of early-onset depression with selective serotonin reuptake inhibitors (SSRIs) has contributed to this hopeful trend [[2]Olfson M. Shaffer D. Marcus S.C. Greenberg T. Relationship between antidepressant medication treatment and suicide in adolescents.Arch Gen Psychiatry. 2003; 60: 978-982Crossref PubMed Scopus (358) Google Scholar]. The authors are concerned about the increased use of SSRIs, and report, but do not highlight a dramatic, eight-fold decline in the use of tricyclic antidepressants (TCAs). This is also a good thing. Tricyclic antidepressants do not seem to work well for pediatric depression, and pose a much higher risk for fatality in overdose [[3]Hazell P. O’Connell D. Heathcote D. et al.Efficacy of tricyclic drugs in treating child and adolescent depression a meta-analysis.BMJ. 1995; 310: 897-901Crossref PubMed Scopus (276) Google Scholar]. This trend shows that physicians are almost never prescribing ineffective and potentially dangerous medications. Concern is also raised about a lack of diagnostic specificity, insofar as an increasing proportion of young patients treated with antidepressants received diagnoses other than major depression, such as depression not otherwise specified (NOS) or dysthymic disorder. However, this does not necessarily reflect lack of specificity, but could indicate greater sensitivity to depressive conditions in general. In fact, the prognosis for dysthymic disorder is worse than for major depression alone, with substantially longer episode lengths and a high risk for the development of “double depression,” which is a chronic condition that is much more difficult to treat than uncomplicated major depression [[4]Kovacs M. Presentation and course of major depressive disorder during childhood and later years of the life span.J Am Acad Child Adolesc Psychiatry. 1996; 35: 705-715Abstract Full Text PDF PubMed Scopus (333) Google Scholar]. Subsyndromal depression, such as depression NOS, is associated with substantial functional impairment and, without treatment, is likely to progress to full-blown depression [5Fergusson D.M. Horwood L.J. Ridder E.M. Beautrais A.L. Subthreshold depression in adolescence and mental health outcomes in adulthood.Arch Gen Psychiatry. 2005; 62: 66-72Crossref PubMed Scopus (565) Google Scholar, 6Clarke G.N. Hawkins W. Murphy M. et al.Targeted prevention of unipolar depressive disorder in an at-risk sample of high school adolescents a randomized trial of group cognitive intervention.J Am Acad Child Adolesc Psychiatry. 1995; 34: 312-321Abstract Full Text PDF PubMed Scopus (517) Google Scholar]. Furthermore, practitioners do appear to be discriminating between milder and more serious depressions, insofar as those with “depressive adjustment disorder” were nine times less likely to receive antidepressants than were those with other, presumably more serious diagnoses. One issue that evinced the authors’ concern was the increasing off-label use of antidepressants. Although fluoxetine is the only Food and Drug Administration (FDA)-approved agent for pediatric depression, 40% of patients will not respond to this medication, and others may not tolerate it [[7]March J.S. Silva S. Petrycki S. et al.Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression Treatment for Adolescent Depression Study (TADS) randomized controlled trial.JAMA. 2004; 292: 807-820Crossref PubMed Scopus (1385) Google Scholar]. Thus, the use of other antidepressants often becomes one of the only alternatives. It is certainly improper that so many of the studies of these antidepressants have not been published. Still, in reviewing the extant data, which has now been made public, citalopram was more efficacious than placebo in one of two trials, sertraline more efficacious than placebo in two trials combined, and paroxetine in one of three trials [8Wagner K.D. Ambrosini P. Rynn M. et al.Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder two randomized controlled trials.JAMA. 2003; 290: 1033-1041Crossref PubMed Scopus (348) Google Scholar, 9Keller M. Ryan N.D. Strober M. et al.Efficacy of paroxetine in the treatment of adolescent major depression a randomized, controlled study.J Am Acad Child Adolesc Psychiatry. 2001; 40: 762-772Abstract Full Text Full Text PDF PubMed Scopus (530) Google Scholar, 10Wagner K.D. Robb A.S. Findling R.L. et al.A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents.Am J Psychiatry. 2004; 161: 1079-1083Crossref PubMed Scopus (255) Google Scholar]. Closer inspection of the paroxetine trials shows that in one of the two unpublished trials, there was an effect for adolescents, but not for children. Similarly, although the unpublished trials using venlafaxine are negative, a re-analysis of the data looking just at adolescents showed a significant drug effect [[11]Emslie G.J. Findling R.L. Yeung P.P. et al.Efficacy and safety of venlafaxine ER in children and adolescents with major depressive disorder. 2004Google Scholar]. Overall, antidepressants show a modest but significant impact on depression compared with placebo (number needed to treat [NNT] = 9) [[12]Bridge J.A. Salary C.R. Birmaher B. et al.The risks and benefits of antidepressant treatment for youth depression.Ann Med. 2005; (in press.)PubMed Google Scholar]. The FDA analyses do show an approximate 1.8-fold increase in suicidality in drug versus placebo, but the overall rate was low, of around 4% on medication versus 2% on placebo, which translates to an NNH (number needed to harm) = 50 [[13]U.S. Food and Drug Administration. FDA issues public health advisory entitled: Reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder (MDD). Available from: www.fda.gov/bbs/topics/answers/2003/ans01256.html.Google Scholar]. Almost all of the reported suicidality involved an increase in ideation, with very few attempts, and no completions in trials involving over 4300 subjects. The adolescent suicide rate has declined as SSRI use has increased, so it is unlikely that the association of SSRIs and suicidality has had a significant negative public health impact [[14]Brent D.A. Antidepressants and pediatric depression the risk of doing nothing.N Engl J Med. 2004; 351: 1598-1601Crossref PubMed Scopus (102) Google Scholar]. The second issue of concern raised by Ma and colleagues was the decline in the use of psychotherapy. This study used a physician-based sampling frame and assessed the prevalence of psychotherapy “ordered” by the physician. It has become increasingly common for non-medical therapists to refer patients to a physician for possible medication treatment rather than the reverse [[15]Druss B.G. Marcus S.C. Olfson M. et al.Trends in care by nonphysician clinicians in the United States.N Engl J Med. 2003; 348: 130-137Crossref PubMed Scopus (143) Google Scholar]. It is possible that referrals from non-medical therapists were not recorded in this study as if the patient was receiving psychotherapy. However, the decline in the use of psychotherapy may be real, following a national trend in the treatment of depression [[16]Olfson M. Marcus S.C. Druss B. Pincus H.A. National trends in the use of outpatient psychotherapy.Am J Psychiatry. 2002; 159: 1914-1920Crossref PubMed Scopus (149) Google Scholar]. The Academy of Child and Adolescent Psychiatry’s guidelines do recommend initial treatment with psychotherapy, particularly specifically indicated therapies such as cognitive behavior therapy (CBT) and interpersonal therapy, neither of which is widely available in most communities [[17]Birmaher B. Brent D.A. Work Group on Quality IssuesPractice parameters for the assessment and treatment of children and adolescents with depressive disorders.J Am Acad Child Adolesc Psychiatry. 1998; 37: 63S-83SPubMed Scopus (229) Google Scholar]. The guidelines do note that in the absence of the availability of indicated psychotherapies, use of medication is a reasonable first step, a view also supported by the Society for Adolescent Medicine [[18]Lock J. Walker L.R. Rickert V.I. Katzman D.K. Suicidality in adolescents being treated with antidepressant medications and the black box label position paper of the Society for Adolescent Medicine.J Adolesc Health. 2005; 36: 92-93Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar]. This view is bolstered by the unfortunate news that fluoxetine was much more efficacious for the treatment of adolescent depression than CBT in the Treatment of Adolescent Depression Study (TADS) [[7]March J.S. Silva S. Petrycki S. et al.Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression Treatment for Adolescent Depression Study (TADS) randomized controlled trial.JAMA. 2004; 292: 807-820Crossref PubMed Scopus (1385) Google Scholar]. Although the TADS study’s initial conclusions were a seemingly common-sense recommendation for combined treatment, this is not justified by the results, nor is it practical, given the lack of availability of qualified therapists. Although combined treatment resulted in the most rapid symptom relief, there were no statistically significant differences between combined treatment and medication alone in either proportion that were significantly clinically improved, or in baseline-adjusted symptom endpoints. The article by Ma and colleagues is timely and gives us a good idea of where we have been. Although the lack of published data on safety and efficacy of commonly used antidepressants is not an acceptable situation, the practice patterns captured herein seem to give some cause for optimism: more depressed young patients are being identified and treated, perhaps earlier in their “depressive careers,” medication is not being prescribed for adjustment disorders, and SSRIs rather than the less efficacious and more dangerous TCAs predominate. What do we need to accomplish in the future? We need complete transparency and rapid publication of all clinical trials, with a careful analysis of risk and benefits. Specific, indicated psychotherapies, although efficacious in some hands, are far from universally available. We need to identify the active elements in psychosocial treatments that can be offered easily, reliably, and quickly, and provide them in a convenient manner, such as on-site in schools or in primary care settings [19Asarnow J.R. Jaycox L.H. Duan N. et al.Effectiveness of a quality improvement intervention for adolescent depression in primary care clinics a randomized controlled trial.JAMA. 2005; 293: 311-319Crossref PubMed Scopus (369) Google Scholar, 20Mufson L. Dorta K.P. Wickramaratne P. et al.A randomized effectiveness trial of interpersonal psychotherapy for depressed adolescents.Arch Gen Psychiatry. 2004; 61: 577-584Crossref PubMed Scopus (399) Google Scholar]. Given the extant data, lack of availability of skilled therapists, and family and patients’ reluctance at times to engage in psychotherapy, the provision of medical management of pediatric and adolescent depression is a reasonable and reasonably safe alternative. See page 434 for the article discussed in this editorial, J. Ma et al. “Depression Treatment during Outpatient Visits by U.S. Children and Adolescents.” See page 434 for the article discussed in this editorial, J. Ma et al. “Depression Treatment during Outpatient Visits by U.S. Children and Adolescents.” Depression treatment during outpatient visits by U.S. children and adolescentsJournal of Adolescent HealthVol. 37Issue 6PreviewDepression affects approximately 2–8% of all children and adolescents, and treatment of depression in children and adolescents has been the center of recent serious debates. We examined national trends in depression visits and treatment among outpatients aged 7 to 17 years. Full-Text PDF
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