Los antidepresivos en pediatría: ¿el mayor fracaso de la asistencia sanitaria?

Se dice que los servicios de salud mental infantil son el mayor fracaso de la sanidad británica; en particular, en lo que respecta al tratamiento de la depresión y las conductas suicidas en niños y adolescentes. El uso de los antidepresivos en niños y adolescentes ilustra la mayor brecha existente en los servicios sanitarios entre práctica médica y evidencias científicas, entre estudios de diseño abierto que reivindican beneficios y un gran número de ensayos clínicos aleatorizados (ECA) que señalan lo contrario, y entre los estudios ECA tal como se publican y publicitan y lo que en realidad demuestran sus datos. Sin embargo, los antidepresivos se usan de forma habitual y, probablemente, son los fármacos más prescritos en la adolescencia. Se examina el contexto del uso de antidepresivos en la infancia, el análisis de las pruebas, los daños y riesgos, el aumento de conductas suicidas y otras cuestiones de práctica clínica asociadas. El lugar para la clínica de los ISRS puede estar asociado a su posible efecto “serénico”, distinto al efecto ansiolítico de las benzodiacepinas y antipsicóticos. Considerar este “principio terapéutico” como resultado primario permitiría una mejor comprensión de los datos de los ensayos clínicos y una práctica clínica más equilibrada en su balance riesgo/beneficio. Su aplicación obligaría a un trabajo colaborativo con los pacientes y a un importante grado de autonomía respecto a lo que recogen las guías clínicas. Se analizan los problemas generales de los servicios sanitarios, su sostenibilidad, la promoción de la salud y el uso de medicamentos, ilustrado por el diagnóstico y tratamiento de la depresión infanto-juvenil y otras afecciones, como la osteoporosis, el asma o la hipertensión arterial. Finalmente, se aboga por una campaña de acceso libre a los datos de los ensayos clínicos

Study 329 continuation phase:Safety and efficacy of paroxetine and imipramine in extended treatment of adolescent major depression

OBJECTIVE: This is an analysis of the unpublished continuation phase of Study 329, the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The objectives of the continuation phase were to assess safety and relapse rates in the longer term. The objective of this publication, under the Restoring Invisible and Abandoned Trials (RIAT) initiative, was to see whether access to and analysis of the previously unpublished dataset from the continuation phase of this randomized controlled trial would have clinically relevant implications for evidence-based medicine. METHODS: The study was an eight-week double-blind randomized placebo-controlled trial with a six month continuation phase. The setting was 12 North American academic psychiatry centres, from 20 April 1994 to 15 February 1998. 275 adolescents with major depression were originally enrolled in Study 329, with 190 completing the eight-week acute phase. Of these, 119 patients (43%) entered the six-month continuation phase (paroxetine n = 49; imipramine n = 39; placebo n = 31), in which participants were continued on their current treatment, blinded. As per the protocol, we have looked at rates of relapse (based on Hamilton Depression Scale scores) across both acute and continuation phases, and generated a safety profile for paroxetine and imipramine compared with placebo for up to six months. ANOVA testing (generalized linear model) using a model including effects of site, treatment and site x treatment interaction was applied. Otherwise we used only descriptive statistics. RESULTS: Of patients entering the continuation phase, 15 of 49 for paroxetine (31%), 12 of 39 for imipramine (31%) and 12 of 31 for placebo (39%) completed as responders. Across the study, 25 patients on paroxetine relapsed (41% of those showing an initial response), 15 on imipramine (26%), and 10 on placebo (21%). In the continuation and taper phases combined there were 211 adverse events in the paroxetine group, 147 on imipramine and 100 on placebo. The taper phase had a higher proportion of severe adverse events per week of exposure than the acute phase, with the continuation phase having the fewest events. CONCLUSIONS: The continuation phase did not offer support for longer-term efficacy of either paroxetine or imipramine. Relapse and adverse events on both active drugs open up the risks of a prescribing cascade. The previously largely unrecognised hazards of the taper phase have implications for prescribing practice and need further exploration

The incidence and prevalence of diabetes in patients with serious mental illness in North West Wales: Two cohorts, 1875–1924 & 1994–2006 compared

<p>Abstract</p> <p>Background</p> <p>Against a background of interest in rates of diabetes in schizophrenia and related psychoses and claims that data from historical periods demonstrate a link that antedates modern antipsychotics, we sought to establish the rate of diabetes in first onset psychosis and subsequent prevalence in historical and contemporary cohorts.</p> <p>Methods</p> <p>Analysis of two epidemiologically complete databases of individuals admitted for mental illness. 3170 individuals admitted to the North Wales Asylum between 1875–1924 and tracked over 18,486 patient years and 394 North West Wales first admissions for schizophrenia and related psychoses between 1994 and 2006 and tracked after treatment.</p> <p>Results</p> <p>The prevalence of Type 2 diabetes among patients with psychoses at time of first admission in both historical and contemporary samples was 0%. The incidence of diabetes remained 0% in the historical sample throughout 15 years of follow-up but rose in the contemporary sample after 3, 5 and 6 years of treatment with an incidence rate double the expected population rate so that the 15 year prevalence is likely to be over 8%.</p> <p>Conclusion</p> <p>No association was found between diabetes and serious mental illness, but there may be an association between diabetes and treatment.</p

Food choice phenotypes : causes and consequences of habitual food selection

The primary aim of this thesis was to investigate the characteristics of individuals defined by their contrasting habitual selection of high fat and low fat foods. Previous studies have applied the term phenotype to this classification. The first study aimed to further characterise the eating patterns of lean high fat (HF-L) and low fat (LF) consumers. It was shown that HF-L consumed much higher amounts of fat (and energy) during the latter part of the evening (Ch 5). HF-L have to deal with this metabolic load late on in the day and during sleep. This may be the reason for a somewhat inferior sleep quality (reflected in a higher heart rate). The second study aimed to investigate i) whether HF-L and LF have different patterns of physiological satiety signals (and therefore a different modulation of appetite control) and ii) to examine the impact of short-term changes to the habitual diet on hunger and satiety. HF-L and LF were both found to be less hungry following consumption of the meal most dissimilar to their habitual diet; perhaps indicating an up-regulation of satiety signals related to nutrients least often consumed (Ch. 6). No significant difference on food preference tests was found between the two groups, indicating that the development of the dietary `habit' may be independent of current preference, at least for normal weight individuals. HF-L were shown to significantly increase energy and fat intake following a high fat preload (Ch. 7), indicating a tendency toward overconsumption under certain conditions (independent of hedonic response), and therefore representing a risk factor for obesity. In HF consumers high fat foods seemed to further disinhibit appetite leading to enhanced consumption. The aim of the third study (Ch. 8) was to define a cluster of characteristics that might ultimately diagnose susceptibility and resistance to dietary induced obesity. A third high fat-overweight phenotype (HF-O) was introduced in order to further investigate how body weight might be influenced by a high fat diet. The results of the free-living study found that both HF-O and HF-L appear to make similar habitual dietary choices in terms of energy and macronnutrient intakes, yet have (by definition) very different body compositions. One issue raised here concerns the validity of the instrument used to define dietary intakes. For example, when using the FFQ, a selection of larger portion sizes would give rise to an underestimation of energy intake from this tool. This may be the case with HF-O who were found to score more highly on the TFEQ disinhibition factor. Studies in Ch. 9 and Ch. 10 indicated that HF-O actually consume greater amounts of food than HF-L and LF in a test meal situation, and display heightened hedonic responses to certain high fat foods. It may be assumed that the pleasure yielded by food influences the expression of food preferences and that these factors are important in influencing food choices (confirmed by descriptive reports in Ch. 10). If food is perceived as more pleasant then this would stimulate more eating through an increased sensation of hunger and a consequent weakening of satiety. A form of qualitative analysis was applied in Ch. 10 to explore motives to eat outside of laboratory conditions. Interestingly, attitudes and intentions were poor predictors of their actual behaviour, suggesting that food choice is not under socio-cognitive control. Therefore a more unconscious or psychobiological explanation of human food selection, emphasising the interaction between biology and behaviour, may be appropriate. The final study (Ch. 11) specifically targeted motives for eating based on the distinction between liking and wanting. What characterises individual's susceptibility to weight gain? HF-O receive pleasure from eating but in comparison to their lean counterparts this might be termed a `super' sensitive hedonic response to food and particularly to high fat (savoury) foods. They show a directed preference for high fat foods coupled with increased levels of disinhibition. This susceptibility to overeating along with the hedonic response to food may be responsible for the increase in meal size demonstrated in experimental situations. Small but consistent overeating is probably one of the main reasons why some individuals are overweight. It appears to be the case that psychological and physiological dispositions of the subject will effect preferences and responses to the qualities of foods (Stubbs et al, 2002), and that the interaction between behavioural and metabolic responses influence weight gain (Pagliassotti et al, 1997)

Los antidepresivos en pediatría: ¿el mayor fracaso de la asistencia sanitaria?

Se dice que los servicios de salud mental infantil son el mayor fracaso de la sanidad británica; en particular, en lo que respecta al tratamiento de la depresión y las conductas suicidas en niños y adolescentes. El uso de los antidepresivos en niños y adolescentes ilustra la mayor brecha existente en los servicios sanitarios entre práctica médica y evidencias científicas, entre estudios de diseño abierto que reivindican beneficios y un gran número de ensayos clínicos aleatorizados (ECA) que señalan lo contrario, y entre los estudios ECA tal como se publican y publicitan y lo que en realidad demuestran sus datos. Sin embargo, los antidepresivos se usan de forma habitual y, probablemente, son los fármacos más prescritos en la adolescencia. Se examina el contexto del uso de antidepresivos en la infancia, el análisis de las pruebas, los daños y riesgos, el aumento de conductas suicidas y otras cuestiones de práctica clínica asociadas. El lugar para la clínica de los ISRS puede estar asociado a su posible efecto “serénico”, distinto al efecto ansiolítico de las benzodiacepinas y antipsicóticos. Considerar este “principio terapéutico” como resultado primario permitiría una mejor comprensión de los datos de los ensayos clínicos y una práctica clínica más equilibrada en su balance riesgo/beneficio. Su aplicación obligaría a un trabajo colaborativo con los pacientes y a un importante grado de autonomía respecto a lo que recogen las guías clínicas. Se analizan los problemas generales de los servicios sanitarios, su sostenibilidad, la promoción de la salud y el uso de medicamentos, ilustrado por el diagnóstico y tratamiento de la depresión infanto-juvenil y otras afecciones, como la osteoporosis, el asma o la hipertensión arterial. Finalmente, se aboga por una campaña de acceso libre a los datos de los ensayos clínicos

National suicide rates 1961-2003: Further analysis of nordic data for suicide, autopsies and ill-defined death rates

BACKGROUND: Concerns about the risk-benefit ratio of treatment with antidepressants in the light of recent evidence pointing to a risk of suicide induction during the course of treatment with antidepressants. These concerns have led to a series of recent studies exploring national rates of suicide and correlating these with data on antidepressant consumption. METHODS: We have compared suicide rates in the Nordic countries with autopsy and ill-defined death rates, and antidepressant sales, during the period 1961 through to 2003. RESULTS: There is a close correlation between suicide rates and both autopsy and ill-defined death rates. CONCLUSIONS: The role of autopsies and other factors in the registration of a death as a suicide appear to need further clarification

Historical overview: Kraepelin's impact on psychiatry

This paper reviews the importance Emil Kraepelin put on disease course as a classificatory principle. It then outlines the academic reception of Kraepelin's disease entities outside Germany, charts the uptake of his diagnostic concepts within clinical practice in Britain, and compares data on admissions for bipolar disorders, involutional melancholia and postpartum psychoses to the North Wales asylum during the period Kraepelin was working to data on contemporary admissions in an effort to shed further light on the validity of his diagnostic concepts

Data from: Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence

Objectives: To reanalyse SmithKline Beecham’s Study 329 (published by Keller and colleagues in 2001), the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The reanalysis under the restoring invisible and abandoned trials (RIAT) initiative was done to see whether access to and reanalysis of a full dataset from a randomised controlled trial would have clinically relevant implications for evidence based medicine. Design: Double blind randomised placebo controlled trial. Setting: 12 North American academic psychiatry centres, from 20 April 1994 to 15 February 1998. Participants: 275 adolescents with major depression of at least eight weeks in duration. Exclusion criteria included a range of comorbid psychiatric and medical disorders and suicidality. Interventions: Participants were randomised to eight weeks double blind treatment with paroxetine (20-40 mg), imipramine (200-300 mg), or placebo. Main outcome measures: The prespecified primary efficacy variables were change from baseline to the end of the eight week acute treatment phase in total Hamilton depression scale (HAM-D) score and the proportion of responders (HAM-D score ≤8 or ≥50% reduction in baseline HAM-D) at acute endpoint. Prespecified secondary outcomes were changes from baseline to endpoint in depression items in K-SADS-L, clinical global impression, autonomous functioning checklist, self-perception profile, and sickness impact scale; predictors of response; and number of patients who relapse during the maintenance phase. Adverse experiences were to be compared primarily by using descriptive statistics. No coding dictionary was prespecified. Results: The efficacy of paroxetine and imipramine was not statistically or clinically significantly different from placebo for any prespecified primary or secondary efficacy outcome. HAM-D scores decreased by 10.7 (least squares mean) (95% confidence interval 9.1 to 12.3), 9.0 (7.4 to 10.5), and 9.1 (7.5 to 10.7) points, respectively, for the paroxetine, imipramine and placebo groups (P=0.20). There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and cardiovascular problems in the imipramine group. Conclusions: Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base