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Original Article |

Recovery and Recurrence Following Treatment for Adolescent Major Depression FREE

John Curry, PhD; Susan Silva, PhD; Paul Rohde, PhD; Golda Ginsburg, PhD; Christopher Kratochvil, MD; Anne Simons, PhD; Jerry Kirchner, BS; Diane May, MA, MSN; Betsy Kennard, PsyD; Taryn Mayes, MS; Norah Feeny, PhD; Anne Marie Albano, PhD; Sarah Lavanier, PsyD; Mark Reinecke, PhD; Rachel Jacobs, PhD; Emily Becker-Weidman, PhD; Elizabeth Weller, MD; Graham Emslie, MD; John Walkup, MD; Elizabeth Kastelic, MD; Barbara Burns, PhD; Karen Wells, PhD; John March, MD, MPH
Arch Gen Psychiatry. 2011;68(3):263-269. doi:10.1001/archgenpsychiatry.2010.150.
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Published online

Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders among adolescents, with rates of approximately 5.9% among females and 4.6% among males.1 It is associated with functional impairment, risk of suicide, and risk of adult depression.24 Thus, it is important to investigate not only the efficacy of adolescent MDD treatments but also whether they reduce risk of subsequent negative outcomes, especially depression recurrence.

The episodic nature of adolescent MDD is evident across community and clinical samples. In community samples, approximately 75% of MDD episodes end within 6 to 15 months.57However, recurrence rates reach 45% in 6 years.4 In clinical samples, recovery rates 1 year after treatment onset range from 81% to 98%,8,9 but recurrence rates range from 54% in 3 years among outpatients8 to more than 60% in 1 year for inpatients.9

Treatment studies usually report outcomes of response (clinically significant improvement) and remission (no or very few remaining symptoms).10,11 Three clinical trials have also reported rates of recovery (maintenance of remission for an extended period) and recurrence (a new episode following recovery). Emslie et al12 assessed 87 child and adolescent outpatients with MDD 1 year after treatment with fluoxetine hydrochloride or placebo. Eighty-five percent had recovered, but 39% of recovered patients experienced a recurrence. Rates were not reported by initial randomized treatment. Clarke et al13 followed up 64 depressed adolescents treated with cognitive behavioral therapy (CBT). Over 2 years, almost all recovered; however, 22% of recovered adolescents experienced a recurrence. Birmaher et al14 followed up 107 depressed adolescents 2 years after treatment with 1 of 3 psychotherapies. Eighty percent recovered, with no differences among treatments. However, 30% of recovered adolescents had 1 recurrence and 8% had 2 recurrences. Thus, even effective treatments can be followed by recurrence rates of 30% to 40% within 1 to 2 years, with no treatment yet surpassing others in preventing recurrence.

In this study, we investigated recovery from and recurrence of MDD during an extended naturalistic follow-up of participants in the Treatment for Adolescents With Depression Study (TADS). We first described recovery rates over 5 years from TADS baseline, and to facilitate comparison with previous research,14 we tested predictors of recovery by 2 years. Second, we described recurrence rates over the 5-year period and tested predictors of recurrence. Third, we investigated long-term effects of initial treatment and short-term response on recovery or recurrence. Finally, because about 8% to 20% of depressed adolescents are at risk for developing bipolar disorder,8 we described the rate of this outcome in our sample.

The Treatment for Adolescents With Depression Study compared fluoxetine, CBT, and their combination and included a placebo condition. The combination of fluoxetine and CBT was the most efficacious short-term treatment.15 Active treatment groups did not differ in rates of sustained response (75%-88%) or remission (55%-60%) at 9 months following maintenance treatment16,17 or in rates of remission (68%) 1 year later.18 Among adolescents randomized to placebo followed by open treatment, 48% were in remission at 9 months.19

To investigate longer-term recovery and recurrence, we first identified baseline or post–short-term treatment predictors found in 3 studies of recovery following a fluoxetine trial,12 recurrence following inpatient treatment,9 or recovery and recurrence following a psychotherapy trial.14 We included all predictors from these studies except psychotic features,9 an exclusion criterion in TADS. Second, we included variables that had predicted or moderated short-term TADS outcome.20 Third, we included residual symptoms following short-term TADS treatment, which had predicted nonremission after maintenance treatment.17 Finally, because of sex differences in MDD prevalence, we included sex. Potential predictors are shown in Table 1.

Table Graphic Jump LocationTable 1. Potential Predictors of Recovery or Recurrence

Although it is not ethically possible to test long-term treatment effects by withholding treatment from a control group, it is possible to compare groups who responded more or less successfully to short-term treatment.21 We hypothesized that favorable response to short-term treatment would predict higher rates of recovery and lower rates of recurrence. Following the study by Birmaher et al,14 we also tested the hypotheses that treatment with the most efficacious short-term intervention would predict higher rates of recovery and lower rates of recurrence than treatment with other interventions.

RELATIONSHIP OF TADS TO PRESENT STUDY

The Treatment for Adolescents With Depression Study compared fluoxetine, CBT, and their combination with one another across short-term (12 weeks), continuation (6 weeks), and maintenance (18 weeks) treatment and with short-term placebo. Participants (N = 439) were randomized to fluoxetine, CBT, their combination, or placebo. Following short-term treatment, placebo partial responders, nonresponders, or responders who relapsed were offered their TADS treatment of choice. Following maintenance treatment, adolescents were followed up openly for 1 year.18 The present study, Survey of Outcomes Following Treatment for Adolescent Depression (SOFTAD), was an open follow-up extending an additional 3.5 years after the TADS follow-up year. The TADS-SOFTAD period spanned 63 months (21 months of TADS and 42 months of SOFTAD), with diagnostic interviews administered according to the schedule shown in Table 2.

Table Graphic Jump LocationTable 2. Schedule of Diagnostic Interview Assessments During the Treatment for Adolescents With Depression Study and the Survey of Outcomes Following Treatment for Adolescent Depressiona

The design, sample characteristics, and outcomes of TADS have been described previously.15,22,23 Treatment response was defined as an independent evaluator rating of 1 (very much improved) or 2 (much improved), partial response was defined as a rating of 3 (minimally improved), and nonresponse was defined as a rating of 4 or higher on the 7-point Clinical Global Impressions–Improvement scale.24 During TADS, remission was defined as a normalized score (<29) on the Children's Depression Rating Scale–Revised (CDRS-R).25

Participants in SOFTAD were recruited from among all 439 adolescents who had been randomized in TADS. The TADS participants were recruited between spring 2000 and summer 2003. The SOFTAD recruitment occurred from March 8, 2004, to December 20, 2006, with the final assessment completed on December 4, 2008. Recruitment involved recontacting TADS early completers and dropouts and, after March 8, 2004, asking TADS completers to participate. For minors, written parental consent and adolescent assent were obtained. For adults, written consent was obtained from them and from their parents, since parents completed some measures. The Duke University Medical Center and site institutional review boards approved this study.

Initial SOFTAD assessment optimally occurred 27 months after TADS baseline, but participants began assessments at whatever assessment point corresponded most closely to the time of their recruitment. At most, participants could complete 7 SOFTAD assessments at 6-month intervals, of which 5 assessments included diagnostic interviews.

SOFTAD PARTICIPANTS

The SOFTAD participants included 196 adolescents (44.6% of youths randomized in TADS), representing 12 of 13 TADS sites. One site was unable to recruit participants. The sample included 110 females (56.1%). The mean (SD) age at SOFTAD entry was 18 (1.8) years (range, 14-22 years). The sample was 78.6% white, 9.2% Latino, 8.2% African American, and 4.1% other ethnicity. Points of entry into SOFTAD by months since TADS baseline were as follows: month 27 (33.7%), month 33 (21.9%), month 39 (13.8%), month 45 (10.7%), month 51 (9.7%), month 57 (8.2%), and month 63 (2.0%). The modal number of completed SOFTAD assessments was 5, with a mean (SD) of 3.5 (1.5) completed SOFTAD assessments.

CRITERION MEASURES
Diagnoses

The Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime Version (K-SADS-PL)26 was administered at 5 SOFTAD assessment points (Table 2). The Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) was used in TADS and by Birmaher et al14 and assessed mood, anxiety, behavior, eating, substance use, psychotic disorders, and tic disorders using DSM-IV criteria27 for the time since the last TADS or SOFTAD assessment and current MDD episode.

Episodes of MDD

When the K-SADS-PL indicated MDD at any point since the last interview, the interviewer inquired about episode onset (time when the participant met full diagnostic criteria) and, if relevant, offset (time when the participant had no remaining clinically significant MDD symptoms for ≥2 weeks). We used the absence of MDD symptoms on the K-SADS-PL rather than a normalized CDRS-R score to define remission in SOFTAD to facilitate comparison with previous research14 and because participants exceeded CDRS-R age limits.

Definition of Recovery and Recurrence

Consistent with adult criteria and prior adolescent research,14,28 we defined recovery as remission lasting at least 8 weeks, with the exception noted later for recovery during the TADS period. Following recovery, time of MDD recurrence was estimated as the month when 5 or more symptoms again became present.

Although SOFTAD interviews inquired about the time since the preceding TADS or SOFTAD interview, TADS interviews had only inquired about current symptoms. To deal with this limitation, we assumed that an index episode of MDD during the TADS period was in remission if no symptoms were reported on a K-SADS-PL assessment and in recovery if no symptoms were reported at 2 consecutive TADS assessments.

Interviewer Training

The SOFTAD evaluators met the same educational and experience criteria as the TADS evaluators. Certification following didactic training required the following: (1) rating a videotaped standard patient interview, with agreement on presence or absence of MDD, 80.0% agreement on the full MDD criterion set, and agreement on other classes of disorders (eg, anxiety disorder); and (2) rating a site-based interview, subsequently rated at the coordinating center with acceptable reliability, using these same criteria.

Evaluators had monthly conference calls and annually rated a standard patient interview. On these, there was complete agreement between evaluators and coordinating center ratings for diagnosis of MDD since the last interview and 95.6% agreement on current MDD; 91.3% of evaluator ratings exceeded 80.0% agreement on diagnostic criteria.

PREDICTORS OF RECOVERY OR RECURRENCE

The following predictors of recovery and recurrence were measured at TADS baseline. Age, ethnicity, sex, family income, and referral source were reported by participants or parents. Income was dichotomized at $75 000 and ethnicity as white or nonwhite for comparison with previous findings.9,20 For duration of index episode and depression severity, an independent evaluator estimated the duration of the index major depressive episode (MDE) and completed the CDRS-R25 for severity. Adolescents completed the Reynolds Adolescent Depression Scale (RADS).29 For global functioning, the evaluator assigned a rating on the Children's Global Assessment Scale.30 To measure suicidal ideation, adolescents completed the Suicide Ideation Questionnaire–Junior High Version.31 The index for melancholic features included 5 CDRS-R items: anhedonia, insomnia, appetite disturbance, guilt, and psychomotor retardation. Comorbid diagnoses were yielded by the K-SADS-PL. To measure hopelessness, cognitive distortions, and treatment expectancy, adolescents completed the Beck Hopelessness Scale,32 completed the Children's Negative Cognitive Errors Questionnaire,33 and rated their expectations for improvement with fluoxetine, CBT, or their combination. To determine parent-adolescent conflict, adolescents and parents completed the Conflict Behavior Questionnaire.34

The following predictors of recovery were assessed at the end of TADS short-term treatment: CDRS-R scores, RADS scores, Children's Negative Cognitive Errors Questionnaire scores, Beck Hopelessness Scale scores, Children's Global Assessment Scale scores, residual K-SADS MDD symptoms, and Conflict Behavior Questionnaire scores. The latter two were also investigated as predictors of recurrence.

TREATMENT DURING SOFTAD

At each SOFTAD assessment, participants were asked what services they had received (if any) for emotional, behavioral, or substance abuse problems. As part of this review of services, they reported whether they had received psychotherapy or antidepressant medication.

STATISTICAL ANALYSIS

Baseline characteristics of TADS participants who enrolled in SOFTAD (n = 196) were compared with those who did not (n = 243) using general linear models for continuous measures and χ2 test for binary outcomes. Fisher exact test and nonparametric median test were alternatively performed as needed.

Because recovery during the TADS period was estimated on the basis of 2 consecutive symptom-free interviews separated by 3 or 6 months and not, as in SOFTAD, on the basis of a specific month of recovery, we reported the cumulative percentages of recovered subjects in 6-month intervals from TADS baseline. Participants were subdivided into 3 groups: (1) those with persistent depression (baseline MDE never resolved); (2) those with recovery from baseline MDE without recurrence; and (3) those with recovery with recurrence. For comparison with previous research,14 we examined recovery by 2-year follow-up, testing its predictors with logistic regression. Among those who recovered at any point, we examined predictors of recurrence over the 63-month period using logistic regression and reported mean and median time from recovery to recurrence.

All analyses were conducted with SAS version 9.2 statistical software (SAS Institute, Inc, Cary, North Carolina). Non directional hypotheses were tested, with the significance level set at .05 for each test. The α was not adjusted for multiple outcomes or tests owing to the exploratory nature of the investigation.

PRELIMINARY ANALYSES

To determine whether SOFTAD participants represented the full TADS sample, we compared them with TADS participants not in SOFTAD on the variables related to hypothesis testing. Participants and nonparticipants did not differ on percentage of short-term treatment responders (53.6% vs 51.0%, respectively; χ21 = 0.28; P = .60) or initial treatment condition (χ23 = 1.54; P = .67). Figure 1 depicts the number of SOFTAD participants from each condition.

Place holder to copy figure label and caption
Figure 1.

Survey of Outcomes Following Treatment for Adolescent Depression (SOFTAD) patient flow. TADS indicates Treatment for Adolescents With Depression Study; CBT, cognitive behavioral therapy.

Graphic Jump Location

Demographic and clinical comparisons are shown in Table 3. There were few differences. The SOFTAD participants were younger (P = .006), included fewer minority adolescents (P = .04), were more likely to be experiencing their initial episode (P = .02), had fewer total comorbid disorders (P = .04), and had fewer anxiety disorders (P = .04).

Table Graphic Jump LocationTable 3. Treatment for Adolescents With Depression Study Baseline Characteristics of Participants and Nonparticipants in the Survey of Outcomes Following Treatment for Adolescent Depression
RECOVERY

The vast majority of SOFTAD participants recovered from their index MDE during the 63 months (Figure 2). Specifically, 189 (96.4%) recovered and 7 (3.6%) did not. Cumulative recovery rates were as follows: 29.6% at 6 months, 66.3% at 12 months, 84.7% at 18 months, 88.3% at 24 months, 92.3% at 30 months, 94.8% at 36 months, and 96.4% at 42 months. Among the 189 adolescents who recovered, 68.8% had recovered by 1 year after baseline and 91.5% had recovered within 2 years.

Place holder to copy figure label and caption
Figure 2.

Cumulative recovery and recurrence rates. TADS indicates Treatment for Adolescents With Depression Study.

Graphic Jump Location
PREDICTION OF RECOVERY BY 2 YEARS

As hypothesized, recovery by 2 years was significantly more likely for those who were short-term treatment responders (96.2%) than for others (79.1%) (χ21 = 11.02; P < .001). However, it was not associated with the combination of fluoxetine and CBT, any particular treatment, or any baseline variables. Among post–short-term treatment variables, recovery was significantly predicted by less severe evaluator-rated depression (CDRS-R score; χ21 = 12.54; P < .001) and higher global functioning (Children's Global Assessment Scale score; χ21 = 5.48; P = .02). There were trends for lower parent-reported conflict (Conflict Behavior Questionnaire score; χ21 = 3.70; P = .05) and more cognitive distortions (Children's Negative Cognitive Errors Questionnaire score; χ21 = 3.00; P = .08) to predict recovery by year 2. Self-reported depression (RADS score), hopelessness (Beck Hopelessness Scale score), and adolescent-reported conflict (Conflict Behavior Questionnaire score) with the mother or father were not significant predictors (all P > .15).

For 186 participants with complete K-SADS symptom ratings after short-term treatment, any of 7 MDD symptoms (excluding psychomotor or concentration disturbance) was associated with lower probability of recovery in 2 years. With all 7 MDD symptoms in a multivariable logistic regression, the significant predictors were appetite or weight disturbance (χ21 = 1.13; P = .03) and sleep disturbance (χ21 = 1.11; P = .03).

RECURRENCE

Of 189 participants who recovered, 101 (53.4%) remained well throughout the SOFTAD period and 88 (46.6%) had MDD recurrence. Most had 1 recurrence (n = 74), but 12 had 2 recurrences and 2 had 3 recurrences. Figure 2 shows the rate of first recurrence across time. Among all recovered participants, cumulative recurrence rates for years 1 through 4 were 1.6%, 12.2%, 29.6%, and 38.1%, respectively. One year after TADS baseline, only 3.4% of the 88 recurrences had occurred. Corresponding rates for years 2, 3, and 4 were 26.1%, 63.6%, and 81.8%, respectively.

For those with recurrence, the mean (SD) time from recovery to the first recurrence was 22.3 (13.9) months (median, 20.3 months). Time from recovery to recurrence ranged from 2 to 55 months, with cumulative rates as follows: 12.5% at 6 months, 26.1% at 12 months, 40.9% at 18 months, 61.3% at 24 months, 77.3% at 30 months, and 84.9% at 36 months.

PREDICTION OF RECURRENCE

Within the SOFTAD sample of 196 participants, 105 (53.6%) had been full responders to short-term treatment, whereas 91 (46.4%) had not been (54 partial responders and 37 nonresponders). For the 189 participants who recovered, the full response rate was 55.6% and the partial response or nonresponse rate was 44.4%.

Contrary to our hypothesis, the recurrence rate for full responders (45.7%) was not significantly lower than for others (47.6%) (χ21 = 0.07; P = .79). We explored whether the combined group of full and partial responders had a lower recurrence rate than nonresponders. Recurrence rates were 42.9% for full or partial responders and 67.6% for nonresponders, which was a significant difference (χ21 = 4.68; P = .03).

Also contrary to our hypothesis, the recurrence rate for participants receiving the combination of fluoxetine and CBT (49.0%) did not differ from that of others (45.7%) (χ21 = 0.16; P = .69). There were no treatment condition differences in recurrence rates (χ23 = 1.91; P = .59).

ADDITIONAL PREDICTORS OF RECURRENCE

In individual regression models, 4 baseline variables predicted recurrence: sex (χ21 = 10.58; P = .001), self-reported depression (RADS score; χ21 = 6.16; P = .01), suicidal ideation (Suicide Ideation Questionnaire–Junior High Version score; χ21 = 6.88; P = .009), and comorbid anxiety disorder (χ21 = 4.98; P = .03). Among females, 57.0% experienced recurrence, compared with 32.9% of males. Among those with anxiety disorder, 61.9% experienced recurrence compared with 42.2% of others. Participants with recurrence compared with those without recurrence had higher mean (SD) RADS and Suicide Ideation Questionnaire–Junior High Version scores (RADS: 81.5 [14.6] vs 75.7 [15.8], respectively; Suicide Ideation Questionnaire–Junior High Version: 25.4 [21.1] vs 17.4 [18.4], respectively).

In a multivariable regression including these 4 predictors, only female sex remained significant (χ21 = 5.04; P = .02). Anxiety disorder approached significance (χ21 = 3.35; P = .07).

BIPOLAR DISORDER

The emergence of bipolar disorder was relatively rare. Twelve participants (6.1%; 3 males, 9 females) were diagnosed with bipolar I disorder (n = 5), bipolar II disorder (n = 4), or, if the duration was 1 day shorter than the criterion, bipolar disorder not otherwise specified (n = 3). Bipolar outcome was unrelated to treatment condition, but most of these participants (n = 9) had not responded to short-term treatment. One never recovered from the index MDE; the other 11 recovered but had recurrence. In each case, bipolar disorder emerged after the end of the TADS period, at a mean (SD) age of 18.0 (1.4) years. Given the small number, we did not conduct further statistical comparisons.

TREATMENT DURING SOFTAD

During SOFTAD, 83 participants (42.3%) received psychotherapy and 88 (44.9%) received antidepressant medication, each unrelated to TADS treatment condition (P > .05). Each treatment was more likely among participants who had not recovered by 2 years (psychotherapy: χ21 = 5.23; P = .02; medication: χ21 = 4.13; P = .04) and among those with recurrence (psychotherapy: χ21 = 13.77; P < .001; medication: χ21 = 16.00; P < .001) than among those with recovery and no recurrence.

We followed up 196 adolescent participants in TADS, the largest treatment follow-up sample of depressed adolescents to date. Rate of recovery from the index MDE over 5 years from TADS baseline was very high (96.4%), and 88.3% of participants recovered within 2 years. As hypothesized, full short-term treatment response was associated with recovery by 2 years, as were other post–short-term treatment variables: less severe depression, absence of sleep or appetite disturbance, and better functioning. Contrary to our hypothesis, treatment with a combination of fluoxetine and CBT did not predict recovery in 2 years.

Slightly fewer than half of recovered adolescents (46.6%) experienced a recurrence by 5 years after baseline. Contrary to our hypotheses, neither full response to short-term treatment nor treatment with a combination of fluoxetine and CBT reduced the risk of recurrence. However, short-term treatment nonresponders were more likely to experience recurrence than full and partial responders. Females were significantly more likely to have a recurrence than males.

The SOFTAD 2-year recovery rate of 88.3% is comparable to the previously reported rate of 80%.14 Comparisons with previous TADS findings17,18 indicate that remission rates increase and that progress toward recovery continues after treatment ends, consistent with other studies.12,14 This is the second study to indicate that longer-term recovery rates are not superior for adolescents receiving the most efficacious short-term treatment.14 Such findings may be attributed to the episodic nature of depressive disorder and limited variance in 2-year recovery as a comparative index.

The SOFTAD recurrence rate reached 29.6% 3 years after baseline, whereas it had reached this rate 2 years after a previous psychotherapy trial.14 Although sample differences cannot be ruled out, it is possible that incorporating continuation and maintenance treatment within TADS slowed the pace of recurrence. The lower rate of recurrence in TADS is consistent with the previous finding that TADS treatment gains were generally maintained during the first year of follow-up.18 Unfortunately, no treatment has yet been identified that reduces adolescent recurrence rates.

The most robust predictor of recurrence was female sex. Females are more likely than males to experience MDD after approximately age 14 years,35 but to our knowledge this is the first study documenting higher recurrence rates among treated adolescent females. Adult studies do not show a sex difference in recurrence.36 One adolescent community study did show such a difference37 from ages 19 to 23 years. This age range overlaps ours, suggesting that female vulnerability to recurrence may be age related. Factors implicated as potential causes of higher depression rates among postpubertal women include sex steroids,38 long-term environmental stressors, low perceived mastery, and ruminative response style.39 Further research should investigate whether more frequent MDD recurrence among young women is confirmed and, if so, what variables are associated with it.

Anxiety disorder was an individual predictor of recurrence. Anxiety disorders were more frequent among females (28.2%) than among males (15.1%) (χ21 = 4.73; P = .03), likely accounting for the elimination of anxiety disorder as a predictor when considering sex simultaneously. Anxiety disorders also predicted poorer short-term outcome in TADS.20 In depressed adults, anxiety mitigates the effectiveness of antidepressant treatment40 and slows response time to CBT.41 These findings suggest that adolescent MDD with anxiety requires further treatment development.

The rate of bipolar outcome in our sample was lower than in adolescent inpatient samples but similar to rates found among outpatients.8 Our rate likely reflects TADS exclusion of participants for whom a placebo-controlled outpatient study was inappropriate (eg, those with psychotic depression or short-term suicidal risk).

CLINICAL IMPLICATIONS

Our results reinforce the importance of modifying a short-term treatment that leads to partial response or nonresponse because these were associated with less likelihood of recovery in 2 years. A study of adolescent selective serotonin reuptake inhibitor nonresponders showed that augmentation with CBT improved response rates.42 To our knowledge, no parallel study has been completed investigating medication augmentation for incomplete CBT response, but treatment algorithms recommend such augmentation.43 The finding that recurrence rates increased significantly from 2 to 3 years after baseline suggests that recurrence prevention efforts, such as symptom or medication monitoring or CBT booster sessions, may be of value beyond the maintenance period included in TADS.

LIMITATIONS

The most significant limitation of this study is that slightly fewer than half of the TADS participants took part. This likely reflects the difficulty maintaining a sample of adolescents during a period when many are moving away from home. Indeed, SOFTAD participants were somewhat younger than nonparticipants. Nevertheless, they did not differ on most measures, including depression characteristics, initial treatment, short-term treatment response rates, or sex. Participants had fewer anxiety disorders, suggesting that recurrence rates may have been higher if all TADS adolescents had participated.

Two other limitations should be noted. First, there was not a no-treatment condition in TADS. Second, most participants receiving placebo eventually received a TADS treatment,19 and access to treatment was not controlled during SOFTAD. Thus, findings do not reflect the naturalistic course of untreated depression. In a separate report, we will describe participants' treatment utilization in more detail.

In summary, all predictors of recovery by 2 years were associated with clinical status after short-term treatment. Female sex was the most robust predictor of recurrence, indicating the importance of understanding and reducing the vulnerabilities of female adolescents to recurrent episodes.

Correspondence: John Curry, PhD, Duke Child and Family Study Center, Duke University Medical Center, 718 Rutherford St, Durham, NC 27705 (curry005@mc.duke.edu).

Submitted for Publication: February 8, 2010; final revision received July 12, 2010; accepted August 20, 2010.

Published Online: November 1, 2010. doi:10.1001/archgenpsychiatry.2010.150

Author Contributions: Dr Curry had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: Drs Curry and Wells provide training through the REACH Institute. Dr Kratochvil receives grant support from Lilly, Abbott, and Somerset and is a consultant for Lilly, Abbott, Neuroscience Education, AstraZeneca, and Pfizer. Dr Emslie is a consultant for BioBehavioral Diagnostics, Lilly, GlaxoSmithKline, Pfizer, and Wyeth, is a speaker for Forest, and receives research funding from Somerset. Dr Walkup receives research support from Pfizer, Lilly, and Abbott and receives royalties from Oxford University Press and Guilford Press. Dr March owns equity in MedAvante, is a consultant for Pfizer, Wyeth, Bristol-Myers Squibb, and Johnson & Johnson, is an advisor for Pfizer, Lilly, Scion, and Psymetrix, receives research support from Pfizer and Lilly, and receives royalties from MultiHealth Systems, Guilford Press, and Oxford University Press.

Funding/Support: This study was funded by grant R01 MH070494 from the National Institute of Mental Health (Dr Curry).

Role of the Sponsor: The National Institute of Mental Health had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.

Additional Contributions: Benedetto Vitiello, MD, coordinated administration of SOFTAD at the National Institute of Mental Health. We thank participants and the site staff who recruited them, including Margaret Price, Stephenie Frank, MS, and Sue Baab, MSN. We acknowledge the many contributions of the late Dr Elizabeth Weller, a dedicated clinical scientist.

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Birmaher  BBrent  DAKolko  DBaugher  MBridge  JHolder  DIyengar  SUlloa  RE Clinical outcome after short-term psychotherapy for adolescents with major depressive disorder. Arch Gen Psychiatry 2000;57 (1) 29- 36
PubMed Link to Article
March  JSilva  SPetrycki  SCurry  JWells  KFairbank  JBurns  BDomino  MMcNulty  SVitiello  BSevere  JTreatment for Adolescents With Depression Study (TADS) Team, Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial. JAMA 2004;292 (7) 807- 820
PubMed Link to Article
Rohde  PSilva  SGTonev  STKennard  BDVitiello  BKratochvil  CJReinecke  MACurry  JFSimons  ADMarch  JS Achievement and maintenance of sustained response during the Treatment for Adolescents With Depression Study continuation and maintenance therapy. Arch Gen Psychiatry 2008;65 (4) 447- 455
PubMed Link to Article
Kennard  BDSilva  SGTonev  SRohde  PHughes  JLVitiello  BKratochvil  CJCurry  JFEmslie  GJReinecke  MRMarch  JS Remission and recovery in the Treatment for Adolescents With Depression Study (TADS): acute and long-term outcomes. J Am Acad Child Adolesc Psychiatry 2009;48 (2) 186- 195
PubMed Link to Article
March  JSilva  SCurry  JWells  KFairbank  JBurns  BDomino  MVitiello  BSevere  JRiedal  KGoldman  MFeeny  NFindling  RStull  SBaab  SWeller  EBRobbins  MWeller  RAJessani  NWaslick  BSweeney  MDublin  RWalkup  JGinsburg  GKastelic  EKoo  HKratochvil  CMay  DLaGrone  RVaughan  BAlbano  AMHirsch  GSPodniesinki  EChu  AReincecke  MLeventhal  BRogers  GJacobs  RPathak  SWells  JLavanier  SADanielyan  ARohde  PSimons  AGrimm  JFrank  SEmslie  GKennard  BHughes  CMayes  TLRosenberg  DBenazon  NButkus  MBartoi  MTreatment for Adolescents With Depression Study (TADS) Team, The Treatment for Adolescents With Depression Study (TADS): outcomes over 1 year of naturalistic follow-up. Am J Psychiatry 2009;166 (10) 1141- 1149
PubMed Link to Article
Kennard  BDSilva  SGMayes  TLRohde  PHughes  JLVitiello  BKratochvil  CJCurry  JFEmslie  GJReinecke  MAMarch  JSTADS, Assessment of safety and long-term outcomes of initial treatment with placebo in TADS. Am J Psychiatry 2009;166 (3) 337- 344
PubMed Link to Article
Curry  JRohde  PSimons  ASilva  SVitiello  BKratochvil  CReinecke  MFeeny  NWells  KPathak  SWeller  ERosenberg  DKennard  BRobins  MGinsburg  GMarch  JTADS Team, Predictors and moderators of acute outcome in the Treatment for Adolescents With Depression Study (TADS). J Am Acad Child Adolesc Psychiatry 2006;45 (12) 1427- 1439
PubMed Link to Article
Kendall  PCKessler  RC The impact of childhood psychopathology interventions on subsequent substance abuse: policy implications, comments, and recommendations. J Consult Clin Psychol 2002;70 (6) 1303- 1306
PubMed Link to Article
Treatment for Adolescents With Depression Study (TADS) Team, The Treatment for Adolescents With Depression Study (TADS): demographic and clinical characteristics. J Am Acad Child Adolesc Psychiatry 2005;44 (1) 28- 40
PubMed Link to Article
March  JSSilva  SPetrycki  SCurry  JWells  KFairbank  JBurns  BDomino  MMcNulty  SVitiello  BSevere  JTreatment for Adolescents With Depression Study (TADS) Team, The Treatment for Adolescents With Depression Study (TADS): long-term effectiveness and safety outcomes. Arch Gen Psychiatry 2007;64 (10) 1132- 1143
PubMed Link to Article
Guy  W ECDEU Assessment Manual for Psychopharmacology. 2nd Washington, DC US Government Printing Office1976;DHEW publication ABM76- 388
Poznanski  EMokros  H Children's Depression Rating Scale–Revised Manual.  Los Angeles, CA Western Psychological Services1996;
Kaufman  JBirmaher  BBrent  DRao  UFlynn  CMoreci  PWilliamson  DRyan  N Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 1997;36 (7) 980- 988
PubMed Link to Article
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 4thtext revision. Washington, DC American Psychiatric Association2000;
Frank  EPrien  RFJarrett  RBKeller  MBKupfer  DJLavori  PWRush  AJWeissman  MM Conceptualization and rationale for consensus definitions of terms in major depressive disorder: remission, recovery, relapse, and recurrence. Arch Gen Psychiatry 1991;48 (9) 851- 855
PubMed Link to Article
Reynolds  W Professional Manual for the Reynolds Adolescent Depression Scale.  Odessa, FL Psychological Assessment Resources1987;
Shaffer  DGould  MSBrasic  JAmbrosini  PFisher  PBird  HAluwahlia  S A Children's Global Assessment Scale (CGAS). Arch Gen Psychiatry 1983;40 (11) 1228- 1231
PubMed Link to Article
Reynolds  W Professional Manual for the Suicidal Ideation Questionnaire.  Odessa, FL Psychological Assessment Resources1987;
Beck  ATSteer  RA Manual for the Beck Hopelessness Scale.  San Antonio, TX Psychological Corp1993;
Leitenberg  HYost  LWCarroll-Wilson  M Negative cognitive errors in children: questionnaire development, normative data, and comparisons between children with and without self-reported symptoms of depression, low self-esteem, and evaluation anxiety. J Consult Clin Psychol 1986;54 (4) 528- 536
PubMed Link to Article
Prinz  RJ The Assessment of Parent-Adolescent Relations: Discriminating Distressed and Non-distressed Dyads [doctoral dissertation].  Stony Brook State University of New York1977;
Wade  TJCairney  JPevalin  DJ Emergence of gender differences in depression during adolescence: national panel results from three countries. J Am Acad Child Adolesc Psychiatry 2002;41 (2) 190- 198
PubMed Link to Article
Hasin  DSGoodwin  RDStinson  FSGrant  BF Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry 2005;62 (10) 1097- 1106
PubMed Link to Article
Lewinsohn  PMRohde  PSeeley  JRKlein  DNGotlib  IH Natural course of adolescent major depressive disorder in a community sample: predictors of recurrence in young adults. Am J Psychiatry 2000;157 (10) 1584- 1591
PubMed Link to Article
Angold  A Sex and developmental psychopathology. JJ  HudziakIn: ed.Developmental Psychopathology and Wellness: Genetic and Environmental Influences. Arlington, VA American Psychiatric Publishing2008;109- 138
Nolen-Hoeksema  SLarson  JGrayson  C Explaining the gender difference in depressive symptoms. J Pers Soc Psychol 1999;77 (5) 1061- 1072
PubMed Link to Article
Clayton  PJGrove  WMCoryell  WKeller  MHirschfeld  RFawcett  J Follow-up and family study of anxious depression. Am J Psychiatry 1991;148 (11) 1512- 1517
PubMed
Brown  CSchulberg  HCMadonia  MJShear  MKHouck  PR Treatment outcomes for primary care patients with major depression and lifetime anxiety disorders. Am J Psychiatry 1996;153 (10) 1293- 1300
PubMed
Brent  DEmslie  GClarke  GWagner  KDAsarnow  JRKeller  MVitiello  BRitz  LIyengar  SAbebe  KBirmaher  BRyan  NKennard  BHughes  CDeBar  LMcCracken  JStrober  MSuddath  RSpirito  ALeonard  HMelhem  NPorta  GOnorato  MZelazny  J Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial. JAMA 2008;299 (8) 901- 913
PubMed Link to Article
Hughes  CWEmslie  GJCrismon  MLPosner  KBirmaher  BRyan  NJensen  PCurry  JVitiello  BLopez  MShon  SPPliszka  SRTrivedi  MHTexas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder, Texas Children's Medication Algorithm Project: update from Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder. J Am Acad Child Adolesc Psychiatry 2007;46 (6) 667- 686
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Survey of Outcomes Following Treatment for Adolescent Depression (SOFTAD) patient flow. TADS indicates Treatment for Adolescents With Depression Study; CBT, cognitive behavioral therapy.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Cumulative recovery and recurrence rates. TADS indicates Treatment for Adolescents With Depression Study.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Potential Predictors of Recovery or Recurrence
Table Graphic Jump LocationTable 2. Schedule of Diagnostic Interview Assessments During the Treatment for Adolescents With Depression Study and the Survey of Outcomes Following Treatment for Adolescent Depressiona
Table Graphic Jump LocationTable 3. Treatment for Adolescents With Depression Study Baseline Characteristics of Participants and Nonparticipants in the Survey of Outcomes Following Treatment for Adolescent Depression

References

Jane Costello  EErkanli  AAngold  A Is there an epidemic of child or adolescent depression? J Child Psychol Psychiatry 2006;47 (12) 1263- 1271
PubMed
Birmaher  BBridge  JAWilliamson  DEBrent  DADahl  REAxelson  DADorn  LDRyan  ND Psychosocial functioning in youths at high risk to develop major depressive disorder. J Am Acad Child Adolesc Psychiatry 2004;43 (7) 839- 846
PubMed Link to Article
Gould  MSKing  RGreenwald  SFisher  PSchwab-Stone  MKramer  RFlisher  AJGoodman  SCanino  GShaffer  D Psychopathology associated with suicidal ideation and attempts among children and adolescents. J Am Acad Child Adolesc Psychiatry 1998;37 (9) 915- 923
PubMed Link to Article
Lewinsohn  PMRohde  PKlein  DNSeeley  JR Natural course of adolescent major depressive disorder, I: continuity into young adulthood. J Am Acad Child Adolesc Psychiatry 1999;38 (1) 56- 63
PubMed Link to Article
Keller  MBBeardslee  WLavori  PWWunder  JDrs  DLSamuelson  H Course of major depression in non-referred adolescents: a retrospective study. J Affect Disord 1988;15 (3) 235- 243
PubMed Link to Article
Essau  CA Course and outcome of major depressive disorder in non-referred adolescents. J Affect Disord 2007;99 (1-3) 191- 201
PubMed Link to Article
Lewinsohn  PMClarke  GNSeeley  JRRohde  P Major depression in community adolescents: age at onset, episode duration, and time to recurrence. J Am Acad Child Adolesc Psychiatry 1994;33 (6) 809- 818
PubMed Link to Article
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 (6) 705- 715
PubMed Link to Article
Emslie  GJRush  AJWeinberg  WAGullion  CMRintelmann  JHughes  CW Recurrence of major depressive disorder in hospitalized children and adolescents. J Am Acad Child Adolesc Psychiatry 1997;36 (6) 785- 792
PubMed Link to Article
Brent  DAHolder  DKolko  DBirmaher  BBaugher  MRoth  CIyengar  SJohnson  BA A clinical psychotherapy trial for adolescent depression comparing cognitive, family, and supportive therapy. Arch Gen Psychiatry 1997;54 (9) 877- 885
PubMed Link to Article
Emslie  GJRush  AJWeinberg  WAKowatch  RAHughes  CWCarmody  TRintelmann  J A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 1997;54 (11) 1031- 1037
PubMed Link to Article
Emslie  GJRush  AJWeinberg  WAKowatch  RACarmody  TMayes  TL Fluoxetine in child and adolescent depression: acute and maintenance treatment. Depress Anxiety 1998;7 (1) 32- 39
PubMed Link to Article
Clarke  GNRohde  PLewinsohn  PMHops  HSeeley  JR Cognitive-behavioral treatment of adolescent depression: efficacy of acute group treatment and booster sessions. J Am Acad Child Adolesc Psychiatry 1999;38 (3) 272- 279
PubMed Link to Article
Birmaher  BBrent  DAKolko  DBaugher  MBridge  JHolder  DIyengar  SUlloa  RE Clinical outcome after short-term psychotherapy for adolescents with major depressive disorder. Arch Gen Psychiatry 2000;57 (1) 29- 36
PubMed Link to Article
March  JSilva  SPetrycki  SCurry  JWells  KFairbank  JBurns  BDomino  MMcNulty  SVitiello  BSevere  JTreatment for Adolescents With Depression Study (TADS) Team, Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial. JAMA 2004;292 (7) 807- 820
PubMed Link to Article
Rohde  PSilva  SGTonev  STKennard  BDVitiello  BKratochvil  CJReinecke  MACurry  JFSimons  ADMarch  JS Achievement and maintenance of sustained response during the Treatment for Adolescents With Depression Study continuation and maintenance therapy. Arch Gen Psychiatry 2008;65 (4) 447- 455
PubMed Link to Article
Kennard  BDSilva  SGTonev  SRohde  PHughes  JLVitiello  BKratochvil  CJCurry  JFEmslie  GJReinecke  MRMarch  JS Remission and recovery in the Treatment for Adolescents With Depression Study (TADS): acute and long-term outcomes. J Am Acad Child Adolesc Psychiatry 2009;48 (2) 186- 195
PubMed Link to Article
March  JSilva  SCurry  JWells  KFairbank  JBurns  BDomino  MVitiello  BSevere  JRiedal  KGoldman  MFeeny  NFindling  RStull  SBaab  SWeller  EBRobbins  MWeller  RAJessani  NWaslick  BSweeney  MDublin  RWalkup  JGinsburg  GKastelic  EKoo  HKratochvil  CMay  DLaGrone  RVaughan  BAlbano  AMHirsch  GSPodniesinki  EChu  AReincecke  MLeventhal  BRogers  GJacobs  RPathak  SWells  JLavanier  SADanielyan  ARohde  PSimons  AGrimm  JFrank  SEmslie  GKennard  BHughes  CMayes  TLRosenberg  DBenazon  NButkus  MBartoi  MTreatment for Adolescents With Depression Study (TADS) Team, The Treatment for Adolescents With Depression Study (TADS): outcomes over 1 year of naturalistic follow-up. Am J Psychiatry 2009;166 (10) 1141- 1149
PubMed Link to Article
Kennard  BDSilva  SGMayes  TLRohde  PHughes  JLVitiello  BKratochvil  CJCurry  JFEmslie  GJReinecke  MAMarch  JSTADS, Assessment of safety and long-term outcomes of initial treatment with placebo in TADS. Am J Psychiatry 2009;166 (3) 337- 344
PubMed Link to Article
Curry  JRohde  PSimons  ASilva  SVitiello  BKratochvil  CReinecke  MFeeny  NWells  KPathak  SWeller  ERosenberg  DKennard  BRobins  MGinsburg  GMarch  JTADS Team, Predictors and moderators of acute outcome in the Treatment for Adolescents With Depression Study (TADS). J Am Acad Child Adolesc Psychiatry 2006;45 (12) 1427- 1439
PubMed Link to Article
Kendall  PCKessler  RC The impact of childhood psychopathology interventions on subsequent substance abuse: policy implications, comments, and recommendations. J Consult Clin Psychol 2002;70 (6) 1303- 1306
PubMed Link to Article
Treatment for Adolescents With Depression Study (TADS) Team, The Treatment for Adolescents With Depression Study (TADS): demographic and clinical characteristics. J Am Acad Child Adolesc Psychiatry 2005;44 (1) 28- 40
PubMed Link to Article
March  JSSilva  SPetrycki  SCurry  JWells  KFairbank  JBurns  BDomino  MMcNulty  SVitiello  BSevere  JTreatment for Adolescents With Depression Study (TADS) Team, The Treatment for Adolescents With Depression Study (TADS): long-term effectiveness and safety outcomes. Arch Gen Psychiatry 2007;64 (10) 1132- 1143
PubMed Link to Article
Guy  W ECDEU Assessment Manual for Psychopharmacology. 2nd Washington, DC US Government Printing Office1976;DHEW publication ABM76- 388
Poznanski  EMokros  H Children's Depression Rating Scale–Revised Manual.  Los Angeles, CA Western Psychological Services1996;
Kaufman  JBirmaher  BBrent  DRao  UFlynn  CMoreci  PWilliamson  DRyan  N Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 1997;36 (7) 980- 988
PubMed Link to Article
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. 4thtext revision. Washington, DC American Psychiatric Association2000;
Frank  EPrien  RFJarrett  RBKeller  MBKupfer  DJLavori  PWRush  AJWeissman  MM Conceptualization and rationale for consensus definitions of terms in major depressive disorder: remission, recovery, relapse, and recurrence. Arch Gen Psychiatry 1991;48 (9) 851- 855
PubMed Link to Article
Reynolds  W Professional Manual for the Reynolds Adolescent Depression Scale.  Odessa, FL Psychological Assessment Resources1987;
Shaffer  DGould  MSBrasic  JAmbrosini  PFisher  PBird  HAluwahlia  S A Children's Global Assessment Scale (CGAS). Arch Gen Psychiatry 1983;40 (11) 1228- 1231
PubMed Link to Article
Reynolds  W Professional Manual for the Suicidal Ideation Questionnaire.  Odessa, FL Psychological Assessment Resources1987;
Beck  ATSteer  RA Manual for the Beck Hopelessness Scale.  San Antonio, TX Psychological Corp1993;
Leitenberg  HYost  LWCarroll-Wilson  M Negative cognitive errors in children: questionnaire development, normative data, and comparisons between children with and without self-reported symptoms of depression, low self-esteem, and evaluation anxiety. J Consult Clin Psychol 1986;54 (4) 528- 536
PubMed Link to Article
Prinz  RJ The Assessment of Parent-Adolescent Relations: Discriminating Distressed and Non-distressed Dyads [doctoral dissertation].  Stony Brook State University of New York1977;
Wade  TJCairney  JPevalin  DJ Emergence of gender differences in depression during adolescence: national panel results from three countries. J Am Acad Child Adolesc Psychiatry 2002;41 (2) 190- 198
PubMed Link to Article
Hasin  DSGoodwin  RDStinson  FSGrant  BF Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry 2005;62 (10) 1097- 1106
PubMed Link to Article
Lewinsohn  PMRohde  PSeeley  JRKlein  DNGotlib  IH Natural course of adolescent major depressive disorder in a community sample: predictors of recurrence in young adults. Am J Psychiatry 2000;157 (10) 1584- 1591
PubMed Link to Article
Angold  A Sex and developmental psychopathology. JJ  HudziakIn: ed.Developmental Psychopathology and Wellness: Genetic and Environmental Influences. Arlington, VA American Psychiatric Publishing2008;109- 138
Nolen-Hoeksema  SLarson  JGrayson  C Explaining the gender difference in depressive symptoms. J Pers Soc Psychol 1999;77 (5) 1061- 1072
PubMed Link to Article
Clayton  PJGrove  WMCoryell  WKeller  MHirschfeld  RFawcett  J Follow-up and family study of anxious depression. Am J Psychiatry 1991;148 (11) 1512- 1517
PubMed
Brown  CSchulberg  HCMadonia  MJShear  MKHouck  PR Treatment outcomes for primary care patients with major depression and lifetime anxiety disorders. Am J Psychiatry 1996;153 (10) 1293- 1300
PubMed
Brent  DEmslie  GClarke  GWagner  KDAsarnow  JRKeller  MVitiello  BRitz  LIyengar  SAbebe  KBirmaher  BRyan  NKennard  BHughes  CDeBar  LMcCracken  JStrober  MSuddath  RSpirito  ALeonard  HMelhem  NPorta  GOnorato  MZelazny  J Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial. JAMA 2008;299 (8) 901- 913
PubMed Link to Article
Hughes  CWEmslie  GJCrismon  MLPosner  KBirmaher  BRyan  NJensen  PCurry  JVitiello  BLopez  MShon  SPPliszka  SRTrivedi  MHTexas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder, Texas Children's Medication Algorithm Project: update from Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder. J Am Acad Child Adolesc Psychiatry 2007;46 (6) 667- 686
PubMed Link to Article

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Beyond Depression
Posted on November 29, 2010
Gili W. Adler Nevo, MD
University of Toronto,
Conflict of Interest: None Declared
The article by Curry et al., published in the online Nov. 1 version of the journal, highlights an important void in youth treatment outcome research. The authors conclude that “Almost all depressed adolescents recovered. However, recurrence occurs in almost half of recovered adolescents”. Careful scrutiny of the literature uncovers a plethora of short to moderate term, but very few long term treatment outcome studies, even when considering what is considered “long term” as brief as two years. Furthermore, not a single long term study was found capable of controlling for confounders by randomization to a control condition.1 Thus, when considering a certain treatment for youth as “evidence based”, is it really “evidence based” or “evidence based solely for short term benefit”? It would not be surprising if we found recurrence, not only in depression, but in the treatment of other psychiatric disorders as well.
The absence of Long-Term-Follow-Up (LTFU) studies is not surprising; LTFUs are very difficult to conduct. Difficulties can be divided into three categories: ethical considerations, methodological issues and organizational difficulties.2-3 We would like to highlight only one from each category (for a more detailed review please see Toner and Steuve’s compelling chapter on the subject).3 Ethically, we could never ask patients to stay in a control condition for long periods of time when an efficacious treatment exists; from an organizational perspective, better alliance and high retention rate is reported in stable conditions.4-10 Population flux in modern western society rarely allows therapists, researchers and patients to stay in the same location for long periods of time, resulting in high attrition rates; and methodologically, the longer the study, the higher the potential for accumulating confounders.
Nevertheless, it is important to evaluate the long term effects of treatment in children and youth. Our goal in child and adolescent mental health is not only immediate symptom reduction, but ensuring the child’s ongoing emotional stability and providing psychological tools that would help her/him move into a happy and productive adulthood. Controlled follow-up studies which span the transition to adulthood and examine multiple aspects of psychological adjustment (including recurrence rates) are essential if we are to determine the true impact of our evidence-based treatments on children’s development.
Reference List
1. Nevo GA, Manassis K. Outcomes for treated anxious children: a critical review of Long-Term-Follow-Up studies. Depress.Anxiety. 2009;26:650-60.
2. Chambless DL, Hollon SD. Defining empirically supported therapies. J.Consult Clin.Psychol. 1998;66:7-18.
3. Toner JA, Stueve AC. Methodological issues in Long-Term Follow Up studies of Chronic Illness. In: Light E, Lebowitz BD, editors. The Elderly with Chronic mental Illness. New York: Springer Publishing Company; 1994. p. 285-320.
4. Heath C. What People Are. Cambridge, Mass: Harvard University Press, 2010:4.
5. Glueck S, Glueck E. Unraveling Juvenile Deliquency. New York Commonwealth Foundation, 2010.
6. Glueck S, Glueck E. Delinquents and Non-Delinquents in Perspective. cambridge, Mass: Harvard University Press, 2010.
7. Terman MD, Oden MH. The Gifted Group at Midlife.Volume: 5 genetic Studies of Genius. Stanford: Stanford University Press; 2010.
8. Oden, M. H. the fulfillment of Promise: 40-year Follow-Up of the Terman Gifted Group. 3-93. 1-1-1968. genetic Psychological Monographs 77. 1-1-1968. Ref Type: Serial (Book,Monograph)
9. Sears RR. The Terman Gifted children Study. Handbook of Longitudinal Research. New York: Praeger; 11984. p. 398-414.
10. Valliant G.E. The Wisdom of the Ego. Cambridge, Mass; London, England: Harvard University Press, 1993.

Conflict of Interest: None declared
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