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It is widely accepted that children and adolescents suffer from depressive disorders. Community surveys indicate an estimated prevalence rate of between 1.8% and 7.8% for depression in adolescents (1,2). Lifetime prevalence rates of major depressive disorder (MDD) in adolescents are estimated to range from 15% to 20%, compared with the adult lifetime rates (2,3). In adolescents, twice as many girls as boys present with MDD (4). In family studies of children and adolescents, first-degree relatives who present with MDD have higher lifetime rates for depression than those expected in the general population (5) or compared with relatives of healthy control subjects (6–15). Depression in adolescents remains underrecognized and misdiagnosed in clinical practice. DSM criteria for adult MDD apply to children and adolescents, with some minor age differences (16–19). There is prospective longitudinal evidence from a birth-cohort study (age, birth to 26 years) to suggest that childhood and adolescent onset of MDD may be distinguished from adult onset of MDD on the basis of early childhood risk factors. These include developmental deficits, family instability, psychopathology and criminality in the biological family, and either inhibited or undercontrolled temperaments in childhood (20). Early onset of depression has been shown to predict future depressive episodes during adolescence and adulthood (21,22). Major depressive episodes in adolescence are long in duration, with a high risk of relapse, and are usually associated with school, family, and social difficulties (23). Community, high risk, and clinical studies have shown that the mean length of an episode of early-onset MDD is 6 to 9 months. The longer the duration, the greater the severity, and the number of maternal depressive episodes has been shown to increase the likelihood of MDD persisting (22,24,25). In a large community study of adolescents, most depressive episodes were brief, with a median of 8 weeks, although a substantial risk of reoccurrence exists (3,4,21,22,26). In adolescent high-risk and clinical samples, the median duration for MDD ranged from 12 to 16 weeks (25). The median duration may represent a more accurate figure, compared with the mean duration, because it is unaffected by methodological variables and extreme scores (25). Clinical and epidemiologic studies indicate that 40% to 93% of children and adolescents with depression have comorbid psychiatric disorders (3,24). Comorbidity with substance use disorders may have a negative effect on severity of MDD symptoms (24,27,28). The impact of comorbidity on MDD duration is less clear (25). The strongest risk factor for adolescent suicide is MDD (29). The longer the duration of MDD, the greater the risk of suicidality (3). Because of the serious morbidity and mortality associated with adolescent MDD, there is a need to investigate the efficacy of interventions. Currently, there is limited evidence that indicates effective therapeutic interventions in child and adolescent depressive disorders. Clinical research is complicated by methodological difficulties, by lack of consensus for testable hypotheses, and by inadequate financial support for research. Placebo-controlled trials of antidepressants and other treatments in child and adolescent populations have been difficult to implement for various reasons, including reluctance to take placebo, concerns with safety and compliance, and high rates of study attrition. PharmacotherapyMultiple open-label pharmacologic trials in adolescents with MDD have shown clinical improvements using tricyclic antidepressants (TCAs)—amitriptyline, nortriptyline, desi- pramine, and imipramine (30–32)—and selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, and sertraline (33–41). Retrospective chart reviews have also provided preliminary evidence on the effectiveness of SSRIs (specifically, fluoxetine, sertraline, and citalopram) in the treatment of adolescent MDD (42–44). Ambrosini and colleagues found that, in a sertraline treatment study of adolescent MDD, maximal clinical response, based on clinician and self-reported depressive symptoms, occurred after week 10, leading them to conclude that, to fully evaluate efficacy, acute-phase antidepressant therapy should extend to at least 10 weeks (37). An open-label study of sertraline in adolescents with MDD who had a minimum 3-month illness duration indicated that maintenance therapy of 6 months was effective in reducing depressive symptoms and in improving functioning (36). An open-label naturalistic study of sertraline in children and adolescent patients with MDD or obsessive–compulsive disorder showed evidence to suggest that the pharmacokinetic profile, tolerability, and recommended titration regime are similar to those in adults (40). A 6-week clinical trial compared open-label fluoxetine treatment in 52 adolescent inpatients with 28 historical control subjects who were treated with imipramine (39). Greater improvements were found with fluoxetine than with imipramine, based on reductions in the Hamilton Depression Rating Scale scores and final scores on the Clinical Global Impression (CGI) scale. The authors concluded that adolescent MDD may respond better to SSRIs than to TCA treatment. Consistently, double-blind randomized controlled trials (RCTs) in adolescent MDD outpatients, comparing TCAs (that is, amitriptyline, nortriptyline, imipramine, and desipramine) with placebo have reported no significant treatment differences (45–51). Response rates to TCAs and to placebo ranged from 40% to 60%. These studies suggest that TCAs are no more effective than are placebos for treating MDD in adolescents. An RCT of intravenous pulse infusion of the TCA clomipramine, however, demonstrated a significant improvement in depressive symptoms and clinical functioning in a small sample of adolescent outpatients with MDD after 6 days, compared with the saline control group (52). After 2 weeks, however, most responders had experienced significant relapse of depressive symptoms that required subsequent SSRI treatment. A review of antidepressant treatment of MDD in children and in adolescents concluded that TCAs were ineffective (53). Previous metaanalysis of TCA treatment of children and adolescent MDD supported the lack of clinical efficacy (54). A recent further metaanalysis by the same authors (55) supported the lack of efficacy of TCAs in the treatment of childhood (that is, prepubertal) MDD. A trend, however, toward a positive treatment response for adolescents was determined with effect-size estimates, suggesting a moderate yet significant treatment benefit for adolescents. The authors concluded that the evidence to support using TCAs in treating adolescent MDD was marginal. Concern has been raised about TCA use; various reports have indicated side effects, particularly cardiovascular adverse events (49,51) and “sudden death” in children taking therapeutic doses (56). Conflicting findings of SSRI efficacy have been reported in RCT studies. An 8-week RCT in 40 adolescents with MDD did not find significant statistical differences between placebo and fluoxetine in response rates (66%), although a trend favoured fluoxetine for response (57). A larger 8-week RCT of fluoxetine treatment in 96 children and adolescent out- patients who presented with MDD reported a significant improvement in MDD on CGI scores, with response rates of 56% for fluoxetine, compared with 33% for placebo control subjects (58). Response rates for children aged 12 years and under (n = 48) did not differ from adolescents aged 13 and over (n = 48). In a subsequent 1-year naturalistic follow-up of 87 patients from this sample, Emslie and colleagues (59) reported that 74 (47 with fluoxetine, 22 without medication, and 5 with other antidepressants or lithium), or 85%, had recovered from the depression during the 1-year period. Unfortunately, 39% experienced a reoccurrence of depression during follow-up. Poor outcome was associated with increased age, severity of depressive symptoms and comorbidity, and decreased family functioning. Recently, in a multicentre study, Emslie and colleagues reported significant improvement in depressive symptoms, remission rates (41% vs 20%), and clinical global functioning in a second RCT of fluoxetine for 9 weeks in 122 children and 97 adolescents with MDD (60). No significant differences were seen based on age category. In January 2003, the US Food and Drug Administration (FDA) approved the use of fluoxetine to treat MDD in children and adolescents (61). In a 12-week, multicentre, international RCT of paroxetine treatment in 286 adolescents with unipolar MDD, statistically significant differences in efficacy were not found between paroxetine and placebo, although there was a trend for adolescents aged 16 years and over to have a higher proportion of paroxetine responders (82.6%), compared with placebo responders (66.7%) (62). A 6-week RCT of low-dose venlafaxine, a selective serotonin norepinephrine reuptake inhibitor (SNRI), in 33 children and adolescents with MDD found significant improvement in depressive symptoms over the study duration, with no difference between venlafaxine and placebo (63). An 8-week, multicentre RCT of paroxetine and imipramine showed efficacy of paroxetine in treating unipolar major depression in 275 adolescents (51). Paroxetine (response rate 63.3%) was superior to placebo (response rate 46%) on clinician ratings of affect, clinical global functioning, and reduction in depressive symptoms. Imipramine (response rate 50%) was not superior to placebo on any outcome measure. In an 8-week, multicentre, double-blind, randomized comparison trial of the efficacy of the SSRI paroxetine and the TCA clomipramine with SRI activity treatments in 122 adolescents with MDD, the response rates were similar (64). Based on a 50% reduction in depression scores, 48.3% responded to clomipramine and 65.1% responded to paroxetine. Similarly, based on CGI scores, 58.2% responded to clomipramine and 59.3% responded to paroxetine. Clomipramine, however, induced significantly more adverse effects than did paroxetine. No placebo control arm was present in the study to confirm efficacy of clomipramine and paroxetine. There have been few small-scale studies that have investigated the effectiveness of SSRI in a specific population of adolescents with MDD and comorbid substance use disorders (SUDs), despite the negative impact that comorbidity with substance use and other disorders has on severity of symptoms and persistence of adolescent MDD (65). An open-label study of the potential safety and efficacy of fluoxetine in 8 adolescent boys with MDD comorbid with conduct and SUD (abstinent for at least 1 month) suggested that fluoxetine may reduce depressive symptoms and increase global functioning (66). In a 12-week RCT of sertraline in 10 adolescents with MDD and alcohol dependence, depressive symptoms and drinking were reduced over the study duration; however, no significant group (that is, sertraline vs placebo) differences were found. These results may have been owing, in part, to concurrent cognitive-behavioural therapy (CBT), which was offered to all study participants regardless of group membership, suggesting CBT efficacy in treating MDD and alcohol dependence (67). Psychosocial TherapiesIn a review of psychosocial therapies for treating depression in children and adolescents, Harrington and coworkers investigated the efficacy of 3 psychotherapies: CBT, interpersonal therapy (IPT), and family therapy (68). CBT involved role playing, problem solving, and monitoring thoughts and behaviours, using behavioural techniques and cognitive strategies. A quantitative metaanalysis that included 6 RCTs with a follow-up component of CBT for predominately nonclinical samples of adolescents with depressive disorders found significant improvement in depressive symptoms in the CBT group (n = 109) over comparison groups (n = 108), including waiting list, supportive therapy, and relaxation techniques (69). Improvements were maintained over the course of the follow-up period (range 1 month to 24 months). A large controlled study of MDD in adolescents (n = 107, completers n = 78), comparing 12 weeks to 16 weeks of individual CBT, nondirective supportive psychotherapy, and systemic behavioural family therapy (70), showed a significant improvement over the study duration for each of the 3 treatments. All 3 treatment groups received family psychoeducation sessions about mental illness and its treatment. Significant differences among treatments began to emerge at 12 to 16 weeks, with the CBT group scoring significantly lower than the supportive therapy group on the Beck Depression Inventory and the CBT group having significantly higher remission rates (60%), compared with the family therapy (29%) and the supportive therapy (36.4%) groups. Adolescents with comorbid anxiety responded better to CBT than to the other 2 psychosocial treatments (71). However, adolescents whose mothers had depressive symptoms negatively impacted the efficacy of CBT (71). In a subsequent follow-up study (72), 45 study participants received additional treatment during the 24-month follow-up phase (62% for depression). The percentage of adolescents from each treatment group who subsequently received additional treatment services did not differ (CBT 48.6%, family therapy 37.1%, and supportive therapy 40%). Predictors of additional treatment included greater ratings of severity for depression at intake, higher frequency of comorbid disruptive disorder, and self-ratings of greater family dysfunction. At 2 years posttreatment, the 3 treatment groups did not differ significantly on depressive symptomatology, clinical global functioning, cognitive variables, or family functioning (73). Increased risk for chronicity and relapse of depression were associated with family conflict and increased severity of MDD (73). Kroll and colleagues investigated weekly maintenance CBT therapy for 6 months in 17 adolescents (74). Results of the study suggested that the relapse risk was lower in adolescents who received continuing CBT (6%) than in those who had not (50%). Community studies of adolescents have shown that group CBT in conjunction with relaxation and group problem-solving therapy may prevent relapses in depression for 9 to 24 months posttreatment (4,75). Children and adolescents with severe depressive disorders did not appear to respond as well to CBT, compared with those who had mild and moderate depression (71,76). IPT is brief, time-limited therapy that identifies and treats the depressive symptoms and the problems associated with depression onset. In a 12-week open trial of IPT in adolescents with depression (77), a decrease in depressive symptoms and an overall improvement in social adjustment were found over the study duration. In a posttreatment study of this sample (78), results strongly suggested that the improvements were maintained over the 1-year follow-up period. A 12-week RCT of the efficacy of IPT in 21 adolescents and in 11 adolescent control subjects who were clinically monitored (79) found that adolescents who received IPT had greater response rates (75%) to treatment than those who were clinically monitored (46%). Further, adolescents who received IPT reported a greater decrease in depressive symptoms, based on clinician and self-rated depression scores, and a greater improvement in overall social functioning, compared with those who received clinical monitoring. At study termination, only 9.1% of the IPT treatment group met criteria for MDD, while 30.3% of individuals in the control subject group showed clinical depression. In a 12-week RCT of 71 Puerto Rican adolescents with depressive disorders (specifically, MDD, dysthymia, or both) comparing CBT and IPT with a wait-list control group (80), both IPT and CBT significantly reduced depressive symptoms on the Children’s Depression Inventory. The IPT enhanced self-esteem and social adaptation. Measures of clinical significance showed that 82% of the adolescents who received IPT and 59% of those who received CBT were in the functional ranges. Family therapy involves more than 1 member of a family and focuses on altering family interactions; therapists work to improve the presenting problem and the relationship patterns associated with the problem. There is strong evidence of an association between depression in children and adolescents and problems in family members, such as mental illness and dysfunctional family relationships (81). A recent 12-week RCT of attachement-based family therapy (ABFT) compared 32 adolescents with MDD to a wait-list control group. ABFT was shown to significantly reduce family conflict, suicidal ideation, and feelings of hopelessness, and to significantly enhance attachment to mothers (82). In addition, at study end, 81% of the adolescents who received ABFT had remitted, compared with 47% from the wait-list control group. For the ABFT group, follow-up at 6 months found that 87% did not meet criteria for MDD. Conversely, RCTs of family therapy in childhood depression have yielded negative results, compared with results of cognitive therapy and supportive counselling (71). Electroconvulsive TherapyElectroconvulsive therapy (ECT) for adolescents presenting with MDD is controversial. Evidence from the adult literature supports ECT as an effective therapy for MDD and other serious mental disorders. In a systematic review of the literature of ECT treatment in those aged 18 years and under, authors suggested that, despite numerous methodological problems, ECT may benefit adolescents who present with depression, mania, schizophrenia, or catatonia (83). Controlled studies of ECT effects in adolescents have not been published to date. DiscussionMany published studies suffer from methodological flaws that limit the study’s conclusions. Conflicting findings in the pharmacologic treatment of adolescent MDD result from methodological factors including limited sample size, variable inclusion criteria, rating issues, dosage ranges, concurrent psychotherapies, and short study duration. Similar methodological problems are found in the research that investigates the effectiveness of various psychosocial therapies for treating adolescent depression. High placebo or comparison therapy response rates rendered the results of many treatment trials difficult to interpret. Despite limitations, current findings from studies investigating SSRIs, CBT, and IPT generally support these therapies as safe and effective first-line treatment in the acute treatment of adolescent MDD. Follow-up of acute-treatment studies of SSRIs and psychosocial therapies has shown that a poorer treatment outcome is associated with increased severity of family dysfunction (59,73). Further efficacy studies are required for specific family therapies in the treatment of adolescents with MDD. In July 2003, Health Canada (84) issued an alert informing health care professionals about the possibility of increased risk of suicide-related and adverse events associated with paroxetine treatment in children and adolescents with MDD. Health Canada notes that the alert is based upon 3 pediatric, placebo-controlled trials. These trials demonstrated that the risk of suicidal thinking, suicidal attempts, and self-harm were 5.3% for the paroxetine group and 2.8% for the placebo group, some of which occurred during discontinuation of paroxetine treatment. There were no completed suicides for any study participant. Further, the trials indicated that paroxetine was no more effective than placebo in the treatment of MDD. It is important to note that the alert did not distinguish any differences in frequency of adverse events or in efficacy between children and adolescents, nor were the cited studies identified. Further analysis is required; however, in the interim, it is recommended that paroxetine treatment not be initiated for children and adolescents with MDD. A preponderance of studies on the efficacy and tolerability of TCAs do not support the use of TCAs in treating adolescent MDD. Some evidence supports a graduated age response to TCA with adolescence; however, TCAs have not been found effective in adolescents with treatment-resistant MDD (45,55). Further study of the efficacy and tolerability of clomipramine, a TCA with serotonin activity (64), is required. There are few follow-up studies of RCT trials. In fact, there is a paucity of studies investigating maintenance therapy and prophylaxis of recurrence. Studies investigating acute and maintenance treatment are required to determine the long-term effects of treatment on outcome in adolescents. Some studies—especially those in which the MDD duration was short—may have been biased toward subjects with mild-to-moderate MDD that resolved naturally and may further account for strong placebo effects. In studies where supportive therapy was not controlled, placebo effects may have resulted. Negative findings are rarely published, yet they add to the understanding of research methods and treatment and may suggest further directions for research, especially within early investigative stages of treatment trials. There is a paucity of studies investigating treatments that combine pharmacotherapy and psychosocial therapies. ConclusionTreating adolescents with depression remains a major clinical and public health challenge with clinically significant recent treatment advances in the areas of pharmacotherapy and psychotherapies. Future investigations into the efficacy and safety of treatments for adolescent depression would benefit greatly from replication, larger sample sizes, and RCT of specific medications, including within classes such as SSRIs, and from psychosocial therapy that extends to acute and long-term treatment phases. Comparison studies of pharmacotherapy, psychotherapies, and combined therapies are necessary to identify the adolescents who will benefit the most from specific or combined therapies. Further studies into the factors that influence treatment outcome—including genetics, age, illness course, duration, and severity—may help identify appropriate treatments and robust effects for adolescents with MDD. Note added in proofWagner and colleagues published the results of a pooled sample from 2 multicentre, 10-week RCT studies of the efficacy and safety of sertraline in 376 children and adolescents with MDD (85). These authors found a response rate of 69% for sertraline, compared with 59% for placebo. There was a significant improvement in depressive symptoms in those treated with sertraline. Evidence of a possible preferential response for adolescents (n = 199) was noted, with a slightly greater improvement in depressive symptoms than was noted for children. No differences in suicidality (in either attempts or ideations) were noted between treatment and placebo groups. The authors concluded that sertraline was a well-tolerated and effective acute treatment for children and adolescents with MDD. This further supports the overall recommendations of the review. Funding and SupportThis paper was supported by the University of Ottawa Medical Research Fund. The Junior Faculty Research Award is held by Dr R Milin. References1. Fleming JE, Offord DR, Boyle MH. Prevalence of childhood and adolescent depression the community. Ontario child health study. Br J Psychiatry 1989;155:647–54. 2. Kessler RC, Walters EE. Epidemiology of DSM-III-R major depression and minor depression among adolescents and young adults in the national comorbidity survey. Depress Anxiety 1998;7:3–14. 3. Birmaher B, Ryan ND, Williamson DE, Brent DA, Kauffman J, Dahl RE, and others. Childhood and adolescent depression: a review of the past 10 years. Part 1. J Am Acad Child Adolesc Psychiatry 1996;35:1427–39. 4. Lewinsohn P, Roberts R, Seeley J, Rohde P, Gotlib I, Hops H. Adolescent psychopathology, II: psychosocial risk factors for depression. J Abnorm Psychol 1994;103:302–15. 5. Strober M. Familial aspects of depressive disorder in early adolescence. In: Weller EB, Weller RA, editors. An update of childhood depression. Washington (DC): APA Press; 1984. p 38–48. 6. Bland RC, Newman SC, Orn H. Recurrent and nonrecurrent depression. A family study. Arch Gen Psychiatry 1986;43:1085–9. 7. Kupfer DJ, Frank E, Carpenter LL, Neiswanger K. Family history in recurrent depression. J Affect Disord 1989;17:113–9. 8. Marazita ML, Neiswanger K, Cooper M, Zubenko GS, Giles DE, Frank E, and others. Genetic segregation analysis of early-onset recurrent unipolar depression. Am J Hum Genet 1997;61:1370–8. 9. Merikangas KR, Risch NJ, Weissman MM. Comorbidity and co-transmission of alcoholism, anxiety and depression. Psychol Med 1994;24:69–80. 10. Weissman MM, Leckman JF, Meikangas KR, Gammon GD, Prusoff BA. Depression and anxiety disorders in parents and children. Results from the Yale family study. Arch Gen Psychiatry 1984;41:845–52. 11. Williamson DE, Ryan ND, Birmaher B, Dahl RE, Kaufman J, Rao U, and others. A case-control family history study of depression in adolescents. J Am Acad Child Adolesc Psychiatry 1995;34:1596–1607. 12. Mitchell J, McCauley E, Burke P. Psychopathology in parents of depressed children and adolescents. J Am Acad Child Adolesc Psychiatry 1989;28:352–7. 13. Puig-Antich J, Goetz D, Davies M, Kaplan T, Davies S, Ostrow L, and others. A controlled family history study of prepubertal major depression disorder. Arch Gen Psychiatry 1989;46:406–18. 14. Weller RA, Kapadia P, Weller EB, Fristad M, Lazaroff LB, Preskorn SH. Psychopathology in families of children with major depressive disorders. J Affect Disord 1994;31:247–52. 15. Klein DN, Lewinsohn PM, Seeley JR, Rohde P. A family study of major depressive disorder in a community sample of adolescents. Arch Gen Psychiatry 2001;58:13–20. 16. 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;35:701–15. 17. Roberts RE, Lewinsohn PM, Seeley JR. Symptoms of DSM-III-R major depression in adolescence: Evidence from an epidemiological survey. J Am Acad Child Adolesc Psychiatry 1995;34:1608–17. 18. Carlson GA, Kashani JH. Phenomenology of major depression from childhood through adulthood: analysis of three studies. Am J Psychiatry 1988;145:1222–5. 19. Ryan N, Puig-Antich J, Ambrosini P, Rabinovich H, Robinson D, Nelson B, and others. The clinical picture of major depression in children and adolescents. Arch Gen Psychiatry 1987;44:854–61. 20. Jaffe SE, Moffitt TE, Caspi A, Fombonne E, Poulton R, Martin J. Differences in early childhood risk factors for juvenile-onset and adult-onset depression. Arch Gen Psychiatry 2002;59:215–22. 21. Harrington RC, Fudge H, Rutter M, Pickles A, Hill J. Adult outcomes of childhood and adolescent depression: I. Psychiatric status. Arch Gen Psychiatry 1990;47:465–73. 22. Kovacs M, Feinberg TL, Crouse-Novak MA, Paulauskas SL, Finkelstein R. Depressive disorders in childhood. II. A longitudinal study of the risk for a subsequent major depression. Arch Gen Psychiatry 1984;41:643–9. 23. Simeon JG. Depressive disorders in children and adolescents. Psychiatr J Univ Ott 1989;14:356–61. 24. Goodyer IM, Herbert J, Secher SM, Pearson J. Short-term outcome of major depression: I comorbidity and severity at presentation as predictors of persistent disorder. J Am Acad Child Adolesc Psychiatry 1997;36:179–87. 25. Kaminski KM, Garber J. Depressive spectrum disorders in high-risk adolescents: episode duration and predictors of time to recovery. J Am Acad Child Adolesc Psychiatry 2002;41:410–8. 26. Goodyer IM, Herbert J, Tamplin A, Secher SM, Pearson J. Short-term outcome of major depression: II life events, family dysfunction, and friendship difficulties as predictors of persistent disorder. J Am Acad Child Adolesc Psychiatry 1997;36:474–80. 27. King CA, Ghaziuddin N, McGovern L, Brand E, Hill E, Naylor M. Predictors of comorbid alcohol and substance abuse in depressed adolescents. J Am Acad Child Adolesc Psychiatry 1996;35:745–51. 28. King CA, Naylor M, Hill E, Shain B, Greden J. Dysthymia characteristic of heavy alcohol use in depressed adolescents. Biol Psychiatry 1993;33:210–2. 29. Brent DA, Perper JA, Moritz G, Allman C, Friend A, Roth C, and others. Psychiatric risk factors for adolescent suicide: a case-control study. J Am Acad Child Adolesc Psychiatry 1993;32:521–9. 30. Ambrosini PJ, Bianchi M, Metz C, Rabinovich H. Evaluating clinical response of open nortriptyline pharmacotherapy in adolescent major depression. J Child Adolesc Psychopharmacol 1994;4:233–44. 31. Ryan N, Puig-Antich J, Cooper T, Rabinovich H, Ambrosini P, Davies M, and others. Imipramine in adolescent depression: plasma level and clinical response. Acta Psychiatr Scand 1986;73:275–88. 32. Strober M, Freeman R, Rigali J. The pharmacotherapy of depressive illness in adolescence: I. An open label trial of imipramine. Psychopharmacol Bull 1990;26:80–4. 33. Boulos C, Kutcher S, Gardner D, Young E. An open naturalistic trial of fluoxetine in adolescents and young adults with treatment-resistant major depression. J Child Adolesc Psychopharmacol 1992;2:103–11. 34. Colle L, Belair J-F, DiFeo M, Weiss J, LaRoche C. Extended open-label fluoxetine treatment of adolescents with major depression. J Child Adolescent Psychopharmacol 1994;4:225–32. 35. McConville B, Minnery K, Sorter M, West S, Friedman L, Christian K. An open study of the effects of sertraline on adolescent major depression. J Child Adolesc Psychopharmacol 1996;6:41–51. 36. Nixon MK, Milin R, Simeon, JG, Cloutier P, Spenst W. Sertraline effects in adolescent major depression and dysthymia: A 6-month open trial. J Child Adolesc Psychopharmacol 2001;11:131–42. 37. Ambrosini PJ, Wagner KD, Biederman J, Glick I, Tan C, Elia J, and others. Multicenter open-label sertraline study in adolescent outpatients with major depression. J Am Acad Child Adolesc Psychiatry 1999;38:566–72. 38. Rey-Sanchez F, Gutierrez-Casares J. Paroxetine in children with major depressive disorder: an open trial. J Am Acad Child Adolesc Psychiatry 1997;36:1443–7. 39. Strober M, DeAntonio M, Schmidt-Lackner S, Pataki C, Freeman R, Rigali J, and others. The pharmacotherapy of depressive illness in adolescents: an open-label comparison of fluoxetine with imipramine-treated historical controls. J Clin Psychiatry 1999;60:164–9. 40. Alderman J, Wolkow R, Chung M, Johnston HF. Sertraline treatment of children and adolescents with obsessive–compulsive disorder or depression: pharmacokinetics, tolerability, and efficacy. J Am Acad Child Adolesc Psychiatry 1998;37:386–94. 41. Findling RL. Open-label treatment of comorbid depression and attentional disorders with co-administration of serotonin reuptake inhibitors and psychostimulants in children, adolescents, and adults: a case series. J Child Adolesc Psychopharmacol 1996;6:165–75. 42. Jain U, Birmaher B, Garcia M, Al-shabbout M, Ryan N. Fluoxetine in children and adolescents with mood disorders: a chart review of efficacy and adverse effects. J Child Adolesc Psychopharmacol 1992;2:259–65. 43. Tierney E, Joshi P, Illinas J, Rosenberg L, Riddle M. Sertraline for major depression in children and adolescents: preliminary clinical experience. J Child Adolesc Psychopharmacol 1995;5:13–27. 44. Bostic JQ, Prince J, Brown K, Place S. A retrospective study of citalopram in adolescents with depression. J Child Adolesc Psychopharmacol 2001;11:159–66. 45. Birmaher B, Waterman GS, Ryan ND, Perel J, McNabb J, Balach L, and others. Randomized, controlled trial of amitriptyline versus placebo for adolescents with”treatment-resistant” major depression. J Am Acad Child Adolesc Psychiatry 1998;37:527–35. 46. Boulos CM, Kutcher S, Marton P, Simeon J, Ferguson B, Roberts N. Response to desipramine treatment in adolescent major depression. Psychopharmacol Bull 1991;27:59–65. 47. Geller B, Cooper TB, Graham DL, Marsteller FA, Bryant DM. A double-blind placebo-controlled study of nortriptyline in depressed adolescents using a “fixed plasma level” design. Psychopharmacol Bull 1990;26:85–90. 48. Kramer A, Feiguine R. Clinical effects of amitriptyline in adolescent depression: a pilot study. J Am Acad Child Adolesc Psychiatry 1981;20:636–44. 49. Kutcher S, Boulos C, Ward B, Marton P, Simeon J, Ferguson B, and others. Response to desipramine treatment in adolescent depression: a fixed-dose, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry 1994;33:686–94. 50. Kye CH, Waterman GS, Ryan N, Birmaher B, Williamson DE, Iyengar S, and others. A randomized, controlled trial of amitriptyline in the acute treatment of adolescent depression. J Am Acad Child Adolesc Psychiatry 1996;35:1139–44. 51. Keller MB, Ryan ND, Strober M, Klein RG, Kutcher SP, Birmaher B, and others. Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry 2001;40:762–72. 52. Sallee FR, Vrindavanam NS, Deas-Nesmith D, Carson SW, Sethuraman G. Pulse intravenous clomipramine for depressed adolescents: double-blind, controlled trial. Am J Psychiatry 1997;154:668–73. 53. Ryan ND, Varma D. Child and adolescent mood disorders—experience with serotonin-based therapies. Biol Psychiatry 1998;44:336–40. 54. Hazell P, O’Connell D, Heathcote D, Robertson J, Henry D. Efficacy of tricyclic drugs in treating child and adolescent depression: a meta-analysis. Br Med J 1995;310:897–901. 55. Hazell P, O’Coneel D, Heathcote D, Henry D. Tricyclic drugs for depression in children and adolescents (Cochrane Review). The Cochrane Library, Issue 4. Oxford: Update Software; 2002. 56. Riddle M, Geller B, Ryan N. Another sudden death in a child treated with desipramine. J Am Acad Child Adolesc Psychiatry 1993;32:792–7. 57. Simeon J, Dinicola V, Ferguson B, Copping W. Adolescent depression: a placebo-controlled fluoxetine treatment study and follow-up. Prog Neuro-Psychopharmacol Biol Psychiatry 1990;14:791–5. 58. Emslie G, Rush J, Weinberg W, Kowatch R, Hughes C, Carmody T, and others. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 1997;54:1031–7. 59. Emslie G, Rush J, Weinberg W, Kowatch R, Carmody T, Mayes T. Fluoxetine in child and adolescent depression: Acute and maintenance treatment. Depress Anxiety 1998;7:32–9. 60. Emslie GJ, Heiligenstein JH, Wagner KD, Hoog SL, Ernest DE, Brown E, and others. Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial. J Am Acad Child Adolesc Psychiatry 2002;41:1205–15. 61. US Food and Drug Administration. FDA approves Prozac for pediatric use to treat depression and OCD. FDA Talk Paper 2003; January 3. 62. Milin RP. Paroxetine studied in adolescents with major depression. The Brown University Child and Adolescent Psychopharmacology Update 2000;2:6–7. 63. Mandoki MW, Tapia MR, Sumner GS, Parker JL. Venlafaxine in the treatment of children and adolescents with major depression. Psychopharmacol Bull 1997;33:149–54. 64. Braconnier A, Coent RL, Cohen D. Paroxetine versus clomipramine in adolescents with severe major depression: a double-blind, randomized, multicenter trial. J Am Acad Child Adolesc Psychiatry 2003;42:22–9. 65. Goodyer IM, Herbert J, Secher SM, Pearson J. Short-term outcome of major depression: I. Comorbidity and severity a presentation as predictors of persistent disorder. J Am Acad Child Adolesc Psychiatry 1997;36:179–87. 66. Riggs PD, Mikulick SK, Coffman LM, Crowley TJ. Fluoxetine in drug- dependent delinquents with major depression: an open trial. J Adolesc Child Psychopharmacol 1997;7:87–95. 67. Deas D, Randall CL, Roberts JS, Anton RF. A double-blind, placebo-controlled trial of sertraline in depressed adolescent alcoholics: A pilot study. Hum Psychopharmacol Clin Exp 2000;15:461–9. 68. Harrington R, Whittaker J, Shoebridge P. Psychological treatment of depression in children and adolescents. A review of treatment research. Br J Psychiatry 1998;173:291–8. 69. Reinecke MA, Ryan NE, DuBois DL. Cognitive-behavioural therapy of depression and depressive symptoms during adolescence: a review and meta-analysis. J Am Acad Child Adolesc Psychiatry 1998;37:26–34. 70. Brent DA, Holder D, Kolko D, Birmaher B, Baugher M, Roth C, and others. A clinical psychotherapy trial for adolescent depression comparing cognitive, family and supportive therapy. Arch Gen Psychiatry 1997;54:877–85. 71. Brent DA, Kolko D, Birmaher B, Baugher M, Bridge J, Roth C, and others. Predictors of treatment efficacy in a clinical trial of three psychosocial treatments for adolescent depression. J Am Acad Child Adolesc Psychiatry 1998;37:906–14. 72. Brent DA, Kolko DJ, Birmaher B, Baugher M, Bridge J. A clinical trial for adolescent depression: predictors of additional treatment in the acute and follow-up phases of the trial. J Am Acad Child Adolesc Psychiatry 1999;38:263–70. 73. Birmaher B, Brent DA, Kolko D, Baugher M, Bridge J, Holder D, and others. Clinical outcome after short-term psychotherapy for adolescents with major depressive disorder. Arch Gen Psychiatry 2000;57:29–36. 74. Kroll L, Harrington R, Jayson D, Fraser J, Gowers S. Pilot study of continuation cognitive-behavioural therapy for major depression in adolescent psychiatric patients. J Am Acad Child Adolesc Psychiatry 1996;35:1156–61. 75. Lerner M, Clum G. Treatment of suicide ideators: a problem-solving approach. Behav Ther 1990;21:403–11. 76. Jayson D, Wood A, Kroll L, Fraser J, Harrington R. Which depressed patients respond to cognitive-behavioural treatment. J Am Acad Child Adolesc Psychiatry 1998;37:35–9. 77. Mufson L, Moreau D, Weissman MM, Wickramaratne P, Martin J, Samoilov A. Modification of interpersonal psychotherapy with depressed adolescents (IPT-A): Phase I and II studies. J Am Acad Child Adolesc Psychiatry 1994;33:695–705. 78. Mufson L, Fairbanks J. Interpersonal psychotherapy for depressed adolescents: a one-year naturalistic follow-up study. J Am Acad Child Adolesc Psychiatry 1996;35:1145–55. 79. Mufson L, Weissman MM, Moreau D, Garfinkel R. Efficacy of interpersonal psychotherapy for depressed adolescents. Arch Gen Psychiatry 1999;56:573–9. 80. Rossello J, Bernal G. The efficacy of cognitive-behavioral and interpersonal treatments for depression in Puerto Rican adolescents. J Consult Clin Psychol 1999;67:734–45. 81. Harrington R. Family-genetic findings in child and adolescent depressive disorders. Int Rev Psychiatry 1996;8:355–68. 82. Diamond GS, Reis BF, Diamond GM, Siqueland L, Isaacs L. Attachment-based family therapy for depressed adolescents: a treatment development study. J Am Acad Child Adolesc Psychiatry 2002;41:1190–6. 83. Rey JM, Walter G. Half a century of ECT use in young people. Am J Psychiatry 1997;154:595–602. 84. Health Canada. Important drug safety information: until further information is available, Paxil (paroxetine hydrochloride) should not be used in children and adolescents under 18 years of age. 2003; July 1–3. 85. Wagner KD, Ambrosini P, Rynn M, Wohlberg C, Yang R, Greenbaum MS, and others. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder. Two randomized controlled trials. JAMA 2003;290:1033–41. Author(s)Received October 2002, revised, and accepted January 2003. 1. Assistant Professor, University of Ottawa; Clinical Director, Regional Children’s Mental Health Centre, Royal Ottawa Hospital, Ottawa, Ontario. 2. Research Associate, Child and Adolescent Psychiatry, Royal Ottawa Hospital, Ottawa, Ontario. 3. Former Research Assistant, Child and Adolescent Psychiatry, Royal Ottawa Hospital, Ottawa, Ontario. Address for correspondence: Dr R Milin, Clinical Director, Regional Children’s Mental Health Centre, Royal Ottawa Hospital, 1145 Carling Avenue, Ottawa, ON K1Z 7K4 email: rmilin@rohcg.on.ca
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