Remission and Recovery in the Treatment for Adolescents With Depression Study (TADS): Acute and Long-Term Outcomes

ObjectiveWe examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS).MethodThe TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder to 12 weeks of treatment with fluoxetine, cognitive–behavioral therapy, their combination, or pill placebo. The pill placebo group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at weeks 12 (acute phase remitters) and 18 (continuation phase remitters) are summarized. We also examined whether residual symptoms at the end of 12 weeks of acute treatment predicted later remission.ResultsAt week 36, the estimated remission rates for intention-to-treat cases were as follows: combination, 60%; fluoxetine, 55%; cognitive–behavioral therapy, 64%; and overall, 60%. Paired comparisons reveal that, at week 24, all active treatments converge on remission outcomes. The recovery rate at week 36 was 65% for acute phase remitters and 71% for continuation phase remitters, with no significant between-treatment differences in recovery rates. Residual symptoms at the end of acute treatment predicted failure to achieve remission at weeks 18 and 36.ConclusionsMost depressed adolescents in all three treatment modalities achieved remission at the end of 9 months of treatment.     

Mixture Toxicity Indices in acute lethal toxicity tests

The use of Mixture Toxicity Indices (MTI's) is one of the more attractive approaches for describing and predicting the effects of mixtures of toxicants. For an MTI to apply to all possible mixtures of the compounds in question, it must summarize information from a model describing all possible responses of interest. A method of obtaining MTI's from response surface equations or from tolerance models similar to the toxic units model is presented. Methods of calculating several MTI's with desirable properties from multivariable probit response surfaces are demonstrated.     

Regional haemodynamic effects of human and rat adrenomedullin in conscious rats.

1. Male, Long Evans rats were chronically instrumented with pulsed Doppler flow probes and intravascular catheters to permit assessment of the regional haemodynamic responses to human and rat adrenomedullin, to compare the responses to human adrenomedullin to those of human alpha-CGRP in the absence and presence of the CGRP1-receptor antagonist, human alpha-CGRP [8-37], and to determine the involvement of nitric oxide (NO)-mediated mechanisms in the responses to human adrenomedullin, relative to human alpha-CGRP. 2. Human and rat adrenomedullin (0.3, 1, and 3 nmol kg-1, i.v.) caused dose-dependent hypotension and tachycardia, accompanied by increases in renal, mesenteric and hindquarters flows and vascular conductances. At the lowest dose only, the hypotensive and mesenteric vasodilator effects of rat adrenomedullin were significantly greater than those of human adrenomedullin. 3. Human alpha-CGRP at a dose of 1 nmol kg-1 caused hypotension, tachycardia and increases in hindquarters flow and vascular conductance, but reduction in renal and mesenteric flows, and only transient vasodilatations in these vascular beds. These effects were substantially inhibited by human alpha-CGRP [8-37] (100 nmol kg-1 min-1), but those of human adrenomedullin (1 nmol kg-1) were not; indeed, the mesenteric haemodynamic effects of the latter peptide were enhanced by the CGRP1-receptor antagonist. 4. In the presence of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 183 nmol kg-1 min-1), there was only a slight, but significant, inhibition of the hindquarters hyperaemic vasodilator effect of human adrenomedullin, but not that of human alpha-CGRP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tics moderate treatment outcome with sertraline but not cognitive-behavior therapy in pediatric obsessive-compulsive disorder.

BACKGROUND: The presence of a comorbid tic disorder may predict a poorer outcome in the acute treatment of pediatric obsessive-compulsive disorder (OCD). METHODS: Using data from the National Institute of Mental Health (NIMH)-funded Pediatric OCD Treatment Study (POTS) that compared cognitive-behavior therapy (CBT), medical management with sertraline (SER), and the combination of CBT and SER (COMB), to pill placebo (PBO) in children and adolescents with OCD, we asked whether the presence of a comorbid tic disorder influenced symptom reduction on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) after 12 weeks of treatment. RESULTS: Fifteen percent (17 of 112) of patients exhibited a comorbid tic disorder. In patients without tics, results replicated previously published intent-to-treat outcomes: COMB > CBT > SER > PBO. In patients with a comorbid tic disorder, SER did not differ from PBO, while COMB remained superior to CBT and CBT remained superior to PBO. CONCLUSIONS: In contrast to CBT outcomes, which are not differentially impacted, tic disorders appear to adversely impact the outcome of medication management of pediatric OCD. Children and adolescents with obsessive-compulsive disorder and a comorbid tic disorder should begin treatment with cognitive-behavior therapy alone or the combination of cognitive-behavior therapy plus a serotonin reuptake inhibitor.