Cognitive Behavioral Program for the Prevention of Depression in At-Risk Adolescents: Isolating the Effects of Dose.

The current study estimated effects of intervention dose (attendance) of a cognitive behavioral prevention (CBP) program on depression-free days (DFD) in adolescent offspring of parents with a history of depression. As part of secondary analyses of a multi-site randomized controlled trial, we analyzed the complete intention-to-treat sample of 316 at-risk adolescents ages 13-17. Youth were randomly assigned to the CBP program plus usual care (n=159) or to usual care alone (n=157). The CBP program involved 8 weekly acute sessions and 6 monthly continuation sessions. Results showed that higher CBP program dose predicted more DFDs, with a key threshold of approximately 75% of a full dose in analyses employing instrumental variable methodology to control multiple channels of bias. Specifically, attending at more than 75% of acute phase sessions led to 45.3 more DFDs over the 9-month period post randomization, which accounted for over 12% of the total follow-up days. Instrument sets were informed by study variables and external data including weather and travel burden. In contrast, conventional analysis methods failed to find a significant dose-outcome relation. Application of the instrumental variable approach, which better controls the influence of confounding, demonstrated that higher CBP program dose resulted in more DFDs.

Collaborative care for adolescents with depression in primary care: a randomized clinical trial.

IMPORTANCE: Up to 20% of adolescents experience an episode of major depression by age 18 years yet few receive evidence-based treatments for their depression. OBJECTIVE: To determine whether a collaborative care intervention for adolescents with depression improves depressive outcomes compared with usual care. DESIGN: Randomized trial with blinded outcome assessment conducted between April 2010 and April 2013. SETTING: Nine primary care clinics in the Group Health system in Washington State. PARTICIPANTS: Adolescents (aged 13-17 years) who screened positive for depression (Patient Health Questionnaire 9-item [PHQ-9] score ≥10) on 2 occasions or who screened positive and met criteria for major depression, spoke English, and had telephone access were recruited. Exclusions included alcohol/drug misuse, suicidal plan or recent attempt, bipolar disorder, developmental delay, and seeing a psychiatrist. INTERVENTIONS: Twelve-month collaborative care intervention including an initial in-person engagement session and regular follow-up by master's-level clinicians. Usual care control youth received depression screening results and could access mental health services through Group Health. MAIN OUTCOMES AND MEASURES: The primary outcome was change in depressive symptoms on a modified version of the Child Depression Rating Scale-Revised (CDRS-R; score range, 14-94) from baseline to 12 months. Secondary outcomes included change in Columbia Impairment Scale score (CIS), depression response (≥50% decrease on the CDRS-R), and remission (PHQ-9 score <5). RESULTS: Intervention youth (n = 50), compared with those randomized to receive usual care (n = 51), had greater decreases in CDRS-R scores such that by 12 months intervention youth had a mean score of 27.5 (95% CI, 23.8-31.1) compared with 34.6 (95% CI, 30.6-38.6) in control youth (overall intervention effect: F2,747.3 = 7.24, P < .001). Both intervention and control youth experienced improvement on the CIS with no significant differences between groups. At 12 months, intervention youth were more likely than control youth to achieve depression response (67.6% vs 38.6%, OR = 3.3, 95% CI, 1.4-8.2; P = .009) and remission (50.4% vs 20.7%, OR = 3.9, 95% CI, 1.5-10.6; P = .007). CONCLUSIONS AND RELEVANCE: Among adolescents with depression seen in primary care, a collaborative care intervention resulted in greater improvement in depressive symptoms at 12 months than usual care. These findings suggest that mental health services for adolescents with depression can be integrated into primary care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01140464.

Zero Suicide Quality Improvement: Developmental and Pandemic-Related Patterns in Youth at Risk for Suicide Attempts.

The Zero Suicide (ZS) approach to health system quality improvement (QI) aspires to reduce/eliminate suicides through enhancing risk detection and suicide-prevention services. This first report from our randomized trial evaluating a stepped care for suicide prevention intervention within a health system conducting ZS-QI describes 1) our screening and case identification process, 2) variation among adolescents versus young adults; and 3) pandemic-related patterns during the first COVID-19 pandemic year. Between April 2017 and January 2021, youths aged 12-24 with elevated suicide risk were identified through an electronic health record (EHR) case-finding algorithm followed by direct assessment screening to confirm risk. Eligible/enrolled youth were evaluated for suicidality, self-harm, and risk/protective factors. Case finding, screening, and enrollment yielded 301 participants showing suicide risk-indicators: 97% past-year suicidal ideation, 83% past suicidal behavior; 90% past non-suicidal self-injury (NSSI). Compared to young adults, adolescents reported: more past-year suicide attempts (47% vs 21%, p<.001) and NSSI (past 6-months, 64% vs 39%, p<.001); less depression, anxiety, posttraumatic stress, and substance use; and greater social connectedness. Pandemic-onset was associated with lower participation of racial-ethnic minority youths (18% vs 33%, p<.015) and lower past-month suicidal ideation and behavior. Results support the value of EHR case-finding algorithms for identifying youths with potentially elevated risk who could benefit from suicide-prevention services, which merit adaptation for adolescents versus young adults. Lower racial-ethnic minority participation after the COVID-19 pandemic-onset underscores challenges for services to enhance health equity during a period with restricted in-person health care, social distancing, school closures, and diverse stresses.

Sleep Characteristics are Associated with Risk of Treated Diabetes Among Postmenopausal Women.

OBJECTIVE: The purpose of this study was to determine whether sleep characteristics are associated with incidence of treated diabetes in postmenopausal individuals. METHODS: Postmenopausal participants ages 50-79 years reported sleep duration, sleep-disordered breathing, or insomnia at baseline and again in a subsample 3 years later. The primary outcome was self-reported new diagnosis of diabetes treated with oral drugs or insulin at any time after baseline. Multivariable Cox proportional hazards models were used. RESULTS: In 135,964 participants followed for 18.1 (± 6.3) years, there was a nonlinear association between sleep duration and risk of treated diabetes. Participants sleeping ≤5 hours at baseline had a 21% increased risk of diabetes compared with those sleeping 7 hours (adjusted hazard ratio [aHR] 1.21; 95% confidence interval [CI], 1.00-1.47). Those who slept for ≥9 hours had a nonsignificant 6% increased risk of diabetes compared with those sleeping 7 hours (aHR 1.06; 95% CI, 0.97-1.16). Participants whose sleep duration had decreased at 3 years had a 9% (aHR 1.09; 95% CI, 1.02-1.16) higher risk of diabetes than participants with unchanged sleep duration. Participants who reported increased sleep duration at 3 years had a risk of diabetes (HR 1.01; 95% CI, 0.95-1.08) similar to those with no sleep duration change. Participants at high risk of sleep-disordered breathing at baseline had a 31% higher risk of diabetes than those without (aHR 1.31; 95% CI, 1.26-1.37). No association was found between self-reported insomnia score and diabetes risk. CONCLUSIONS: Sleep-disordered breathing and short or long sleep duration were associated with higher diabetes risk in a postmenopausal population.

Defensive startle response to emotional social cues in social anxiety.

Potentiation of fear-related defense behaviours coordinated by the amygdala in response to environmental threat characterizes several anxiety disorders. We compared eye-blink startle responses to startle probes delivered during the presentation of emotional and neutral social cues in high and low generalized social anxiety. Socially anxious individuals exhibited larger startle responses to emotional (positive and negative) relative to neutral social cues, compared to non-anxious individuals.

Crustal rheology of the Himalaya and Southern Tibet inferred from magnetotelluric data.

The Cenozoic collision between the Indian and Asian continents formed the Tibetan plateau, beginning about 70 million years ago. Since this time, at least 1,400 km of convergence has been accommodated by a combination of underthrusting of Indian and Asian lithosphere, crustal shortening, horizontal extrusion and lithospheric delamination. Rocks exposed in the Himalaya show evidence of crustal melting and are thought to have been exhumed by rapid erosion and climatically forced crustal flow. Magnetotelluric data can be used to image subsurface electrical resistivity, a parameter sensitive to the presence of interconnected fluids in the host rock matrix, even at low volume fractions. Here we present magnetotelluric data from the Tibetan-Himalayan orogen from 77 degrees E to 92 degrees E, which show that low resistivity, interpreted as a partially molten layer, is present along at least 1,000 km of the southern margin of the Tibetan plateau. The inferred low viscosity of this layer is consistent with the development of climatically forced crustal flow in Southern Tibet.

Predicting suicide attempts and suicide deaths among adolescents following outpatient visits.

BACKGROUND: Few studies report on machine learning models for suicide risk prediction in adolescents and their utility in identifying those in need of further evaluation. This study examined whether a model trained and validated using data from all age groups works as well for adolescents or whether it could be improved. METHODS: We used healthcare data for 1.4 million specialty mental health and primary care outpatient visits among 256,823 adolescents across 7 health systems. The prediction target was 90-day risk of suicide attempt following a visit. We used logistic regression with least absolute shrinkage and selection operator (LASSO) and generalized estimating equations (GEE) to predict risk. We compared performance of three models: an existing model, a recalibrated version of that model, and a newly-learned model. Models were compared using area under the receiver operating curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: The AUC produced by the existing model for specialty mental health visits estimated in adolescents alone (0.796; [0.789, 0.802]) was not significantly different than the AUC of the recalibrated existing model (0.794; [0.787, 0.80]) or the newly-learned model (0.795; [0.789, 0.801]). Predicted risk following primary care visits was also similar: existing (0.855; [0.844, 0.866]), recalibrated (0.85 [0.839, 0.862]), newly-learned (0.842, [0.829, 0.854]). LIMITATIONS: The models did not incorporate non-healthcare risk factors. The models relied on ICD9-CM codes for diagnoses and outcome measurement. CONCLUSIONS: Prediction models already in operational use by health systems can be reliably employed for identifying adolescents in need of further evaluation.

Augmenting usual care SSRIs with cognitive behavioral therapy for insomnia to improve depression outcomes in youth: Design of a randomized controlled efficacy-effectiveness trial.

IMPORTANCE: Extant treatments for youth depression are only modestly effective. Alternative approaches are needed to improve health outcomes. A novel approach to improve depression outcomes is suggested by epidemiological studies finding that insomnia often predates and may contribute to depression risk. We test whether treating insomnia among youth starting a new course of SSRI antidepressants improves depression outcomes. This paper describes our study design. DESIGN: 2-arm randomized controlled efficacy-effectiveness trial. SETTING: A large non-profit health maintenance organization. PARTICIPANTS: 165 adolescents aged 12-19 with research-confirmed depression and insomnia diagnoses, starting a new episode of selective serotonin reuptake inhibitor (SSRI) antidepressant treatment prescribed by their usual care provider. INTERVENTIONS: Two sleep interventions, each 6-7 sessions, both overlaying "treatment as usual" (TAU) SSRIs: a sleep hygiene (SH) attention control condition, and cognitive-behavioral therapy for insomnia (CBTI). CONCLUSIONS AND RELEVANCE: If CBT-I improved sleep is shown to improve depression-related outcomes, this may provide an additional, easily tolerated intervention for an important public health target. TRIAL REGISTRATION: clinicaltrials.gov, NCT02290496, https://clinicaltrials.gov/ct2/show/NCT02290496.

Using a website to build community and enhance outcomes in a group, multi-component intervention promoting healthy diet and exercise in adolescents.

OBJECTIVE: This article describes website use and behavioral outcomes in a multi-component lifestyle intervention promoting healthy diet and exercise. METHODS: A 2-year randomized clinical trial to improve bone density in 228 adolescent girls, the intervention included a website designed to enhance intervention adherence, retention of participants, and behavioral outcomes. Measures included diet and exercise recalls, surveys, and web-usage data. RESULTS: Website use was associated with increases in calcium intake (ss = 69.72, p =.01, ES = 0.15) and high-impact activity (ss = 10.93, p =.04, ES =.13). Use of web pages related to behavioral feedback and communications was not significantly associated with behavioral outcomes. The most visited website pages had content related to incentive points, caption contests, and fun facts. CONCLUSIONS: Web elements of a multi-component intervention may promote retention and engagement in target behaviors. Such websites may be most acceptable to adolescent participants if they blend fun and behavioral elements, rather than exclusively focusing on behavioral changes.

Randomized effectiveness trial of an Internet, pure self-help, cognitive behavioral intervention for depressive symptoms in young adults.

This study evaluated an Internet-delivered, cognitive behavioral skills training program versus a treatment-as-usual (TAU) control condition targeting depression symptoms in young adults aged 18 to 24 years. Potential participants were mailed a recruitment brochure; if interested, they accessed the study website to complete an online consent and baseline assessment. Intervention participants could access the website at their own pace and at any time. Reminder postcards were mailed periodically to encourage return use of the intervention. The pure self-help intervention was delivered without contact with a live therapist. The primary depression outcome measure was the Patient Health Questionnaire, administered at 0, 5, 10, 16, and 32 weeks after enrollment. A small but significant between-group effect was found from Week 0 to Week 32 for the entire sample (N = 160, d = .20, 95% confidence interval [CI] 0.00-0.50), with a moderate effect among women (n = 128, d .42, 95%C1 = 0.09-0.77). Greater depression reduction was associated with two measures of lower website usage, total minutes, and total number of page hits. Although intervention effects were modest, they were observed against a background of substantial TAU depression pharmacotherapy and psychosocial services. Highly disseminable, low-cost, and self-help interventions such as this have the potential to deliver a significant public health benefit.

Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial.

CONTEXT: Only about 60% of adolescents with depression will show an adequate clinical response to an initial treatment trial with a selective serotonin reuptake inhibitor (SSRI). There are no data to guide clinicians on subsequent treatment strategy. OBJECTIVE: To evaluate the relative efficacy of 4 treatment strategies in adolescents who continued to have depression despite adequate initial treatment with an SSRI. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of a clinical sample of 334 patients aged 12 to 18 years with a primary diagnosis of major depressive disorder that had not responded to a 2-month initial treatment with an SSRI, conducted at 6 US academic and community clinics from 2000-2006. INTERVENTIONS: Twelve weeks of: (1) switch to a second, different SSRI (paroxetine, citalopram, or fluoxetine, 20-40 mg); (2) switch to a different SSRI plus cognitive behavioral therapy; (3) switch to venlafaxine (150-225 mg); or (4) switch to venlafaxine plus cognitive behavioral therapy. MAIN OUTCOME MEASURES: Clinical Global Impressions-Improvement score of 2 or less (much or very much improved) and a decrease of at least 50% in the Children's Depression Rating Scale-Revised (CDRS-R); and change in CDRS-R over time. RESULTS: Cognitive behavioral therapy plus a switch to either medication regimen showed a higher response rate (54.8%; 95% confidence interval [CI], 47%-62%) than a medication switch alone (40.5%; 95% CI, 33%-48%; P = .009), but there was no difference in response rate between venlafaxine and a second SSRI (48.2%; 95% CI, 41%-56% vs 47.0%; 95% CI, 40%-55%; P = .83). There were no differential treatment effects on change in the CDRS-R, self-rated depressive symptoms, suicidal ideation, or on the rate of harm-related or any other adverse events. There was a greater increase in diastolic blood pressure and pulse and more frequent occurrence of skin problems during venlafaxine than SSRI treatment. CONCLUSIONS: For adolescents with depression not responding to an adequate initial treatment with an SSRI, the combination of cognitive behavioral therapy and a switch to another antidepressant resulted in a higher rate of clinical response than did a medication switch alone. However, a switch to another SSRI was just as efficacious as a switch to venlafaxine and resulted in fewer adverse effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00018902.

Overcoming Depression on the Internet (ODIN) (2): a randomized trial of a self-help depression skills program with reminders.

BACKGROUND: Guided self-help programs for depression (with associated therapist contact) have been successfully delivered over the Internet. However, previous trials of pure self-help Internet programs for depression (without therapist contact), including an earlier trial conducted by us, have failed to yield positive results. We hypothesized that methods to increase participant usage of the intervention, such as postcard or telephone reminders, might result in significant effects on depression. OBJECTIVES: This paper presents a second randomized trial of a pure self-help Internet site, ODIN (Overcoming Depression on the InterNet), for adults with self-reported depression. We hypothesized that frequently reminded participants receiving the Internet program would report greater reduction in depression symptoms and greater improvements in mental and physical health functioning than a comparison group with usual treatment and no access to ODIN. METHODS: This was a three-arm randomized control trial with a usual treatment control group and two ODIN intervention groups receiving reminders through postcards or brief telephone calls. The setting was a nonprofit health maintenance organization (HMO). We mailed recruitment brochures by US post to two groups: adults (n = 6030) who received depression medication or psychotherapy in the previous 30 days, and an age- and gender-matched group of adults (n = 6021) who did not receive such services. At enrollment and at 5-, 10- and 16-weeks follow-up, participants were reminded by email (and telephone, if nonresponsive) to complete online versions of the Center for Epidemiological Studies Depression Scale (CES-D) and the Short Form 12 (SF-12). We also recorded participant HMO health care services utilization in the 12 months following study enrollment. RESULTS: Out of a recruitment pool of 12051 approached subjects, 255 persons accessed the Internet enrollment site, completed the online consent form, and were randomized to one of the three groups: (1) treatment as usual control group without access to the ODIN website (n = 100), (2) ODIN program group with postcard reminders (n = 75), and (3) ODIN program group with telephone reminders (n = 80). Across all groups, follow-up completion rates were 64% (n = 164) at 5 weeks, 68% (n = 173) at 10 weeks, and 66% (n = 169) at 16 weeks. In an intention-to-treat analysis, intervention participants reported greater reductions in depression compared to the control group (P = .03; effect size = 0.277 standard deviation units). A more pronounced effect was detected among participants who were more severely depressed at baseline (P = .02; effect size = 0.537 standard deviation units). By the end of the study, 20% more intervention participants moved from the disordered to normal range on the CES-D. We found no difference between the two intervention groups with different reminders in outcomes measures or in frequency of log-ons. We also found no significant intervention effects on the SF-12 or health care services. CONCLUSIONS: In contrast to our earlier trial, in which participants were not reminded to use ODIN, in this trial we found a positive effect of the ODIN intervention compared to the control group. Future studies should address limitations of this trial, including relatively low enrollment and follow-up completion rates, and a restricted number of outcome measures. However, the low incremental costs of delivering this Internet program makes it feasible to offer this type of program to large populations with widespread Internet access.

Cognitive-behavioral treatment of insomnia and depression in adolescents: A pilot randomized trial.

We tested whether augmenting conventional depression treatment in youth by treating sleep issues with cognitive behavioral therapy for insomnia (CBT-I) improved depression outcomes. We randomized youth 12-20 years of age to 10 weekly sessions of a sleep hygiene control condition (SH) combined with CBT for depression (CBT-D) (n = 20), or an experimental condition consisting of CBT-I combined with CBT-D (n = 21). We assessed outcomes through 26 weeks of follow-up and found medium-large effects favoring the experimental CBT-I arm on some sleep outcomes (actigraphy total sleep time and Insomnia Severity Index "caseness") and depression outcomes (higher percentage recovered, faster time to recovery), but little effect on other measures. Total sleep time improved by 99 min from baseline to week 12 in the CBT-I arm, but not in the SH arm. In addition, our pilot yielded important products to facilitate future studies: the youth-adapted CBT-I program; the study protocol; estimates of recruitment, retention, and attrition; and performance and parameters of candidate outcome measures. ClinicalTrials.gov Identifier NCT00949689.

AACAP 2001 research forum: challenges and recommendations regarding recruitment and retention of participants in research investigations.

OBJECTIVE: Clinical research depends on the participation of representative samples. At the 2001 Annual Meeting of the American Academy of Child and Adolescent Psychiatry, the Workgroup on Research conducted a research forum with the purpose of improving recruitment and retention of children and adolescents in research protocols. METHOD: An interdisciplinary group of participants focused on (1) consumers and families, (2) communities, (3) professionals and health care delivery systems, (4) regulatory bodies, and (5) alternative research designs. Obstacles and challenges were identified and solutions were discussed. RESULTS: Key recommendations include the following: Investigators must become involved with community stakeholders and more explicitly communicate with families about research procedures, risks, and benefits; budgets should include explicit items for case management and referrals to families who do not meet entry criteria; the culture of clinical settings must incorporate research conducted by clinicians; regulatory bodies must streamline and coordinate protocols and procedures; designs emphasizing flexible treatment strategies and adaptive treatments should be encouraged; and health care systems should consider changing incentives for research participation, including the radical notion that reimbursement be made in terms of improvement rather than service units. CONCLUSIONS: An integrated approach is recommended, requiring direct involvement of investigators in communities where research is to be conducted.

Physician-patient relations: no more models.

Currently, the common theoretical models of "preferred" decision-making relationships do not correspond well with clinical experience. This interview study of congestive heart failure (CHF) patients documents the variety of patient preferences for decision-making, and the necessity for attention to family involvement. In addition, these findings illustrate the confusion as to the designation of surrogate decision-makers and physicians in charge. We conclude that no single model of physician-patient decision-making should be preferred, and that physicians should first ask patients how they want medical information and decision-making to be handled.

Overcoming depression on the Internet (ODIN): a randomized controlled trial of an Internet depression skills intervention program.

BACKGROUND: Psychoeducational programs are increasingly being delivered over the Internet. We created an Internet-based, cognitive therapy, self-help program to be used as a stand-alone intervention for mild-to-moderate depression, or as an adjunct to traditional services for more severe depression. OBJECTIVE: To evaluate the effectiveness of a web-based intervention program to reduce depression in a randomized, controlled trial. METHODS: In a private, nonprofit health maintenance organization, we mailed recruitment brochures to two populations: depressed adults (n = 6994) who received traditional medical services for depression, and an age/gender matched sample of nondepressed adults (n = 6996). Participants consenting to the study were randomized to either the experimental Web site (n = 144), or a no-access control group (n = 155). Participants in both groups were free to obtain nonexperimental, usual care services for their depression. All participants completed an on-line version of the Center for Epidemiological Studies Depression Scale (CES-D) at enrollment and at 4-, 8-, 16- and 32-weeks after enrollment. Mean intake scores were in the severely depressed range. 74% of participants completed at least one follow-up assessment. Unfortunately, most intervention participants accessed the Internet site infrequently. RESULTS: We failed to find an effect for the Internet program across the entire sample. However, post-hoc, exploratory analyses revealed a modest effect among persons reporting low levels of depression at intake. CONCLUSIONS: The negative results might have resulted from infrequent patient use of the Internet site, or a more seriously depressed sample than the intervention was intended to help. Future studies should focus on recruiting persons with mild to moderate levels of depression, and on increasing participant use of the Internet site.

Evaluating the promise of health IT to enhance/expand the reach of mental health services.

OBJECTIVE: A growing number of health information technologies (HIT) are being developed and tested to address mental health conditions. HIT includes Internet and smartphone programs or apps, text messaging protocols and telepsychiatry. We reviewed the promise and evidence that HIT can expand access to mental health care and reduce disparities in use of services across groups in need. CONCLUSIONS: Limited reach of mental health services is a pervasive problem in the United States, and solving it will require innovations that enable us to extend our clinical reach into underserved populations without significantly expanding our workforce. In theory, HIT can extend access to mental health care in several ways: by enhancing the reach to priority populations, addressing system capacity issues, supporting training, improving clinical decision making, lowering the "consumer's threshold" for treatment, delivering preventive mental health services, speeding innovation and adoption and reducing cost barriers to treatment. At present, evidence is limited, and research is needed, focusing on consumer engagement strategies, the benefits and harms of HIT for the therapeutic relationship and the comparative effectiveness of various HIT alternatives.

Evidence for the management of adolescent depression.

Adolescent depression is a prevalent and disabling condition resulting in emotional suffering and social and educational dysfunction. Care for adolescent depression is suboptimal and could be improved through the development and use of quality indicators (QIs). This article reports on the development of a care pathway and QIs for the primary and specialty care management of adolescent depression from case identification through symptom remission. It presents evidence from a review of adolescent clinical practice guidelines and research literature to support QIs at critical nodes in the pathway, and describes implications for practice based on existing evidence. Barriers to measure development are identified, including gaps in empirical evidence, and a research agenda is suggested.

Impact of treatments for depression on comorbid anxiety, attentional, and behavioral symptoms in adolescents with selective serotonin reuptake inhibitor-resistant depression.

OBJECTIVE: To assess the relative efficacy of antidepressant medication, alone and in combination with cognitive behavioral therapy (CBT), on comorbid symptoms of anxiety, attention, and disruptive behavior disorders in participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial. METHOD: Adolescents with selective serotonin reuptake inhibitor (SSRI)-resistant depression (N = 334) were randomly assigned to a medication switch alone (to another SSRI or to venlafaxine) or to a medication switch plus CBT. Anxiety, attention-deficit/hyperactivity disorder (ADHD), and disruptive behavior disorder (DBD) symptoms were assessed by psychiatric interview and self-report at regular intervals between baseline and 24 weeks. The differential effects of medication and of CBT, and the impact of remission on the course of comorbid symptoms and diagnoses, were assessed using generalized linear mixed models. RESULTS: Remission was associated with a greater reduction in scalar measures of anxiety, ADHD, and DBDs, and a greater decrease in the rate of diagnosed anxiety disorders. The correlations between the changes in symptoms of depression on the CDRS-R and anxiety, ADHD, and oppositional symptoms were modest, ranging from r = 0.12 to r = 0.28. There were no significant differential treatment effects on diagnoses, or corresponding symptoms. CONCLUSION: The achievement of remission had a beneficial effect on anxiety, ADHD, and DBD symptoms, regardless of the type of treatment received. There were no differential effects of medication or CBT on outcome, except for a nonsignificant trend that those adolescents treated with SSRIs showed a greater decrease in rates of comorbid DBDs relative to those treated with venlafaxine. Clinical trial registration information-Treatment of SSRI-Resistant Depression In Adolescents (TORDIA); http://clinicaltrials.gov/; NCT00018902.