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Treatment-resistant depressed youth show a higher response rate if treatment ends during summer school break.

ABSTRACT: OBJECTIVE:There is little work on the effect of school on response to treatment of depression, with available research suggesting that children and adolescents with school difficulties are less likely to respond to fluoxetine compared with those with no school difficulties. METHOD:Depressed adolescents in the Treatment of Resistant Depression in Adolescents study, who had not responded to a previous adequate selective serotonin reuptake inhibitor (SSRI) trial, were randomly assigned to one of the following: another SSRI, venlafaxine, another SSRI + cognitive behavior therapy (CBT), or venlafaxine + CBT. Participants were classified into four groups depending on whether their enrollment in the study and end of treatment was during school or summer vacation. RESULTS:Controlling for baseline differences, adolescents ending their 12-week treatment during summer vacation had odds 1.7 times (95% confidence interval = 1.02-2.8, p = .04) greater to have an adequate response as those ending their treatment while being in school. In addition, adequate depression response was associated with fewer school problems at week 12 (scores <5 versus scores ?5: odds ratio = 3.3, 95% confidence interval = 1.9-5.8, p < .001). There was a significant interaction between school difficulties and timing of treatment, with the lowest rates of response being among adolescents having school difficulties and ending their treatment during the active school year. CONCLUSION:School problems are relevant to treatment response in depressed adolescents and should be incorporated into the treatment plan. These findings also suggest that the time of the year might need to be taken into consideration for analysis of clinical trials in school-aged youth. CLINICAL TRIAL REGISTRATION INFORMATION:Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://www.clinicaltrials.gov; NCT00018902.

SUBMITTER: Shamseddeen W

PROVIDER: S-EPMC3658110 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Treatment-resistant depressed youth show a higher response rate if treatment ends during summer school break.

Shamseddeen Wael W Clarke Gregory G Wagner Karen Dineen KD Ryan Neal D ND Birmaher Boris B Emslie Graham G Asarnow Joan Rosenbaum JR Porta Giovanna G Mayes Taryn T Keller Martin B MB Brent David A DA

Journal of the American Academy of Child and Adolescent Psychiatry 20110909 11

<h4>Objective</h4>There is little work on the effect of school on response to treatment of depression, with available research suggesting that children and adolescents with school difficulties are less likely to respond to fluoxetine compared with those with no school difficulties.<h4>Method</h4>Depressed adolescents in the Treatment of Resistant Depression in Adolescents study, who had not responded to a previous adequate selective serotonin reuptake inhibitor (SSRI) trial, were randomly assign ...[more]

PMID: 22024002

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Project description:BackgroundBortezomib (Bz) is a proteasome inhibitor that directly targets antibody-producing plasma cells. We recently reported the first randomized control trial that evaluated the effects of Bz in patients with systemic lupus erythematosus (SLE). In that study, we demonstrated that Bz treatment is associated with many adverse reactions in patients with refractory disease. In the present study, we examine the therapeutic and toxic effects of Bz on MRL/MpJ-lpr/lpr (MRL/lpr) mice with severe disease activity.MethodsFemale MRL/lpr mice at 10 and 14 weeks of age were treated with phosphate buffered saline (PBS) (n = 19), Bz (750 μg/kg twice weekly) (n = 27), or cyclophosphamide (Cyc) (1 mg/body, once in 2 weeks) (n = 20). Cellular subsets, serum immunoglobulin, anti-double-stranded DNA (anti-dsDNA) antibody titer, and a pathological index of glomerulonephritis were then analyzed at 22 weeks of age. Survival curves of the 10-week-old and 14-week-old Bz-treated groups were compared. Blood counts, creatinine, liver enzymes, and serum cytokine levels were measured 1 week after Bz treatment. Gene expression profiling of spleens from Bz and Cyc treatment mice were compared with those from control mice.ResultsThe anti-dsDNA antibody levels were significantly higher in 14-week-old than in 10-week-old mice, indicating a higher disease activity at 14 weeks. A significant decrease in the number of splenic cells and glomerulonephritis index was observed in Bz-treated and Cyc-treated mice. Bz, but not Cyc, significantly decreased serum immunoglobulin and anti-dsDNA antibody titer levels. Survival curve analysis revealed a significantly higher mortality rate in 14-week-old than in 10-week-old Bz-treated and control groups. Following two injections of Bz, serum IL-6 and TNF-α levels were significantly more elevated in 14-week-old than in 10-week-old mice. Potentially immunogenic molecules, such as heat shock proteins, were characteristically upregulated in spleens of Bz-treated but not Cyc-treated mice.ConclusionsIn spite of its therapeutic effect, Bz treatment had more toxic effects associated with increased proinflammatory cytokine levels in mice with a higher disease activity. Understanding the mechanism of the toxicity and developing preventive strategies against it is important for the safe clinical application of Bz in human SLE.

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Treatment-resistant depressed youth show a higher response rate if treatment ends during summer school break.

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Treatment-resistant depressed youth show a higher response rate if treatment ends during summer school break.

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