DOLESCENT DEPRESSION IS A common, chronic, recurrent, and impairing condition that accounts for a substantial proportion of the disability and mortality incurred in this age group. 1,2 Untreated depression results in impairment in school, interpersonal relationships, occupational adjustment, and in

Objective The purpose of this study was to report on the outcome of participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial after 24 weeks of treatment, including remission and relapse rates and predictors of treatment outcome. Method Adolescents (ages 12–18 years) with selective serotonin reuptake inhibitor (SSRI)-resistant depression were randomly assigned to either a medication switch alone (alternate SSRI or venlafaxine) or a medication switch plus cognitive-behavioral therapy (CBT). At week 12, responders could continue in their assigned treatment arm and nonresponders received open treatment (medication and/or CBT) for 12 more weeks (24 weeks total). The primary outcomes were remission and relapse, defined by the Adolescent Longitudinal Interval Follow-Up Evaluation as rated by an independent evaluator. Results Of 334 adolescents enrolled in the study, 38.9% achieved remission by 24 weeks, and initial treatment assignment did not affect rates of remission. Likelihood of remission was much higher (61.6% versus 18.3% ) and time to remission was much faster among those who had already demonstrated clinical response by week 12. Remission was also higher among those with lower baseline depression, hopelessness, and self-reported anxiety. At week 12, lower depression, hopelessness, anxiety, suicidal ideation, family conflict, and absence of comorbid dysthymia, anxiety, and drug/alcohol use and impairment also predicted remission. Of those who responded by week 12, 19.6% had a relapse of depression by week 24. Conclusions Continued treatment for depression among treatment-resistant adolescents results in remission in approximately one-third of patients, similar to adults. Eventual remission is evident within the first 6 weeks in many, suggesting that earlier intervention among non-responders could be important.

Objective-The authors sought to assess the relationship between candidate genes and two clinical outcomes, namely, symptomatic improvement and the occurrence of suicidal events, in a sample of treatment-resistant depressed adolescents. Method-A subsample of depressed adolescents participating in the Treatment of SSRI-ResistantDepression in Adolescents (TORDIA) trial, 155 of whom were of European origin, were genotyped with respect to 21 polymorphisms on 12 genes that have a reported association with depression, treatment response, or suicidal events. Participants had not responded to a previous adequate trial with an antidepressant and were randomized to receive either another selective serotonin reuptake inhibitor or venlafaxine, with or without cognitive-behavioral therapy (CBT). Single-nucleotide polymorphism (SNP) analyses were conducted using PLINK with permutation procedures.Results-No relationship was observed between any polymorphism and response to treatment. The FKBP5 (which codes for a protein causing subsensitivity of the glucocorticoid receptor) rs1360780TT and rs3800373GG genotypes were associated with suicidal events (N=18), even after controlling for treatment effects and relevant covariates. These two SNPs were in significant linkage disequilibrium (r=0.91).Conclusions-The FKBP5 genotypes associated with suicidal events in this study have been reported by others to cause the greatest degree of glucocorticoid receptor subsensitivity. These results are consistent with those of other studies linking alterations in the hypothalamic-pituitary-adrenal axis with suicidal behavior. The small number of events and lack of a placebo condition make these results preliminary. Replication with a larger sample and a placebo condition is needed to assess whether these events are related to treatment.Clinical guidelines recommend the use of antidepressants for moderate to severe adolescent depression (1). However, even under the controlled conditions of clinical trials, only around 60% of depressed adolescents respond to an initial trial with a selective serotonin reuptake inhibitor (SSRI) (2). The high rate of nonresponse and the occurrence of suicidal events in depressed adolescents are both important clinical concerns (2). In this context, efforts to NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript personalize treatment by identifying which patients are most likely to respond to antidepressants and least likely to experience a suicidal event are of high public health significance. Pharmacogenetics, which examines the relationship between genetic variation and clinical response to a given medication, holds promise for personalizing and optimizing pharmacotherapy.Pharmacogenetic predictors of antidepressant response have primarily focused on the impact of genetic variations in the serotonin transporter promoter gene (SLC64A) and on other serotonin-related receptors because of the mechanisms of action of SSRIs (3). Antidepressant treatment response has been associated with the l...

Objectives: To determine the prevalence of five mental disorders in primary care and to identify patient groups that have a relatively high prevalence of these disorders.Design: Two-stage case identification design that involves administration of a 16-item screening instrument followed by an independent diagnostic assessment.Setting: Three family practice offices in Rhode Island.Subjects: A total of 937 primary care patients completed the brief screen, 388 of whom completed the independent diagnostic assessment.Prevalence Estimation: A Bayesian procedure was used to estimate prevalence of mental disorder from screening and assessment results. Independent assessments were based on the Structured Clinical Interview for DSM\x=req-\ III-R administered by a mental health professional.Results: The prevalence estimates were alcohol abuse or dependence, 3.2%; generalized anxiety disorder, 2.8%; major depressive disorder, 14.1%; obsessive\x=req-\ compulsive disorder, 2.2%; panic disorder, 6.2%; and any of the five disorders, 22.0%. The prevalence of any of the five disorders was higher in patients returning for follow-up visits (27.9%) than in those either presenting with a new illness (21.7%) or seeking a routine physical examination (11.8%). The combined prevalence was also higher in patients with a chronic medical problem (25.8%) than in those without (16.7%).Conclusions: Patients returning for follow-up care and, to a lesser extent, those with chronic medical problems appear to be at increased risk of having a mental disorder. The practice of selectively screening new patients for mental health problems is questioned. Screening efforts in primary care should include established patients and those with chronic medical illnesses as well as new patients.

Objective-The authors used results from a twenty-year, high-intensity follow-up to measure the influence of aging, and of age at onset, on the long-term persistence of symptoms in major depressive disorder (MDD).Method-Subjects who completed a 20-year series of semi-annual and then annual assessments with a stable diagnosis of MDD, or schizoaffective disorder other than mainly schizophrenic, (n = 220), were divided according to their ages at intake into youngest (18-29 years), middle (30-44 years), and oldest (≥45 years) groups. Depressive morbidity was quantified as the proportion of weeks spent in major depressive or schizoaffective episodes. General linear models (GLM) then tested for effects of time and time-by-group interactions on these measures. Regression analyses compared the influence of age of onset and of current age.Results-Analyses revealed no significant time or group-by-time effects on the proportions of weeks in major depressive episodes in any of three age groups. Earlier ages of onset were associated with greater symptom persistence, particularly in the youngest group. The proportions of weeks ill showed intra-individual stability over time that was most evident in the oldest group.Conclusion-These results indicate that the persistence of depressive symptoms in MDD does not change as individuals move from their third to their fifth decade, from their fourth to their sixth decade, or from their sixth to their eighth decade. An early age of onset, rather than youth per se, is associated with greater morbidity over two decades.