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.     

Second Thoughts on Living Wills

Advance directives such as living wills are attractive in that they give us a sense of control over our futures. But they also tend to obscure conflicts between a patient's competent wishes and later, incompetent interests. They allow caregivers to avoid evaluating quality of life in assessing the best interests of incompetent patients.     

The effect of tartrate on bone cell acid phosphatase activity: a quantitative cytochemical study

Tartrate-resistant acid phosphatase activity (TRAPase) is widely used as a cytochemical marker to distinguish osteoclasts from macrophages and other related cell types. The degree of tartrate resistance, however, may depend on which reaction methods, tissues, or species are used. To investigate this further, we have measured the amount of cytochemical reaction product by microdensitometry. We compared osteoclast acid phosphatase (APase) activity in fresh frozen sections of neonatal rat calvaria using two different reaction methods; one is commonly employed for qualitative histochemistry and includes alpha naphthyl phosphate as substrate, simultaneous coupling to the chromagen Fast Garnet, and a 30-minute reaction time (method A). The other may be used to measure enzyme reaction rates in cells in situ and employs conditions suitable for initial velocity kinetics, namely naphthol-ASBI phosphate as substrate, post coupling to Fast Garnet, and a 2-minute reaction time. Although enzyme reaction rates differed greatly between the two methods, significant inhibition of APase activity by tartrate was observed in calvarial osteoclasts (69% and 59% with methods A and B, respectively), osteoblasts, and spleen macrophages. Using method B, mouse calvarial osteoclasts had similar APase activity to that seen in the rat. Tartrate produced little inhibition in these mouse cells, in contrast to the observations made with rat tissue, but murine spleen macrophages were significantly tartrate sensitive (40% inhibition with tartrate). On this basis, conclusions regarding the cell specificity of TRAPase should be treated cautiously.     

Long-term course of epilepsy in a large cohort of intellectually disabled patients.

This study was designed to describe the course of epilepsy (in terms of seizure frequency) and to assess the variables (antiepileptic therapy regimens and others) correlated to improvement. Seizure frequency (categories: seizure free, more than one seizure/year, monthly seizures, weekly seizures and daily seizures) and antiepileptic medication were retrospectively compared between 1992 and 2002 in a large cohort of 550 inpatients with chronic epilepsy and different degrees of intellectual disability or multiple handicaps. RESULTS: Seizure frequency decreased significantly (p<0.001). 218 of the 394 patients (55.3%) not seizure free in 1992 improved (changed into a better frequency category). The improvement rate was marginally higher in patients who had undergone a medication change (p=0.08). A high seizure frequency in 1992 (p=0.016) and older age (p=0.006), but not epilepsy syndrome or degree of intellectual disability, were predictors for improvement (stepwise logistic regression analysis). 56.4% of the improved patients were on combinations of two AEDs (17.4%, monotherapy; 20.2%, triple therapy). The most frequent therapy regimens in the improved patients were lamotrigine/valproate (48 patients), carbamazepine/phenobarbital (21) and carbamazepine only (19). Lamotrigine/valproate was effective in all kinds of epileptic syndromes. Most patients on lamotrigine had serum concentrations above 10microg/ml, approximately one half had dosages above 200mg/day. The rate of seizure freedom increased from 28.4 to 37.6%. The 84% of the patients seizure free in 1992 remained seizure free. Predictors for seizure freedom in 2002 were higher age (stepwise logistic regression, p<0.0005) and seizure freedom in 1992 (p<0.0005). CONCLUSIONS: Substantial improvement can be achieved even in intellectually disabled patients with chronic epilepsy. Although the rate of seizure freedom is reduced in comparison with a non-ID population, once seizure freedom has been achieved it is most likely to continue. For a majority of this patient population, monotherapy may not be sufficient. Lamotrigine/valproate appears to be a major therapeutic innovation.