Inappropriate data and measures lead to questionable conclusions

Letter to the EditorGlen I. Spielmans, Jon Jureidini, David Healy, Robert Pursse

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OBJECTIVE: This is an analysis of the unpublished continuation phase of Study 329, the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the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

BRIDGE study warrants critique

David M. Allen, Peter I. Parry, Robert Purssey, Glen I. Spielmans, Jon Jureidini, Nicholas Z. Rosenlicht, David Healy, Irwin Feinber

Childhood tetanus in Australia: ethical issues for a should-be-forgotten preventable disease

Refusal of a parent to have a child vaccinated against tetanus raised ethical issues for the treating clinicians. The clinicians felt their duty to the child was compromised, but recognised that our society leaves the authority for such decisions with the parents. As there was no reason, other than different beliefs about vaccination, to doubt the parent\u27s care for the child, the clinicians limited their response to providing strong recommendations in favour of vaccination. Other issues raised by this case include community protection, and the costs to the community of treating a vaccine-preventable disease

Educating Health Professionals about Drug and Device Promotion: Advocates' Recommendations

Mansfield and colleagues outline the recommendations from four advocacy groups for improving the education of health professionals on promotion of drugs and devices

Aripiprazole in the Maintenance Treatment of Bipolar Disorder: A Critical Review of the Evidence and Its Dissemination into the Scientific Literature

A systematic search of the literature reveals limited evidence to support use of aripiprazole, a second-generation antipsychotic medication, in maintenance therapy of bipolar disorder, despite widespread use

The black box warning: decreased prescriptions and increased youth suicide?

Full Text: JON JUREIDINI, M.B.B.S., F.R.A.N.Z.C.P., Ph.D. British Columbia, Canada To The Editor: The article by Robert D. Gibbons, Ph.D., et al., published in the September 2007 issue of the Journal, incorrectly analyzed the relationship between U.S. selective serotonin reuptake inhibitor (SSRI) prescription rates and suicide rates among children (1). Dr. Gibbons et al. indicated that there is a correspondence between a 22% decrease in prescriptions after warnings were issued by the Food and Drug Administration (FDA) and the 14% increase in youth suicide rates between 2003 and 2004. They concluded that decreases in prescriptions "were associated with increases in suicide rates in children and adolescents" (1, p. 1357). Unless carefully examined, Figure 1 and Figure 2 in their article create the same impression. However, the data show no such association. In the year in which suicide rates rose sharply, there was no significant drop in SSRI prescribing. This fact is only acknowledged in the Discussion section, where an attempt is made to explain away the inconvenient truth: "While only a small decrease in the SSRI prescription rate for U.S. children and adolescents occurred from 2003 to 2004, the public health warnings may have left some of the most vulnerable youths untreated" (1, p. 1359). The discussion then continues at length as though a clear association (if not causal relationship) has been established, with alarmist predictions regarding the consequences of decreased prescribing. As it turns out, preliminary figures are now available from the Centers for Disease Control (CDC), which show that fewer people under age 25 committed suicide in 2005 (when prescribing did decrease) than in 2004 (2). In the editorial accompanying the article, James F. Leckman, M.D., and Robert A. King, M.D., noted that the authors cited several studies that agreed with their position, but no studies that reported neutral or opposite findings (3). There is no mention of the fact that the suicide rate was already declining before SSRIs were introduced. The 2004 suicide figures were compared simplistically with the previous year, rather than examining the change in trends over several years. The y axes were contracted to make trends appear more impressive and no data tables were provided, and thus it is difficult for readers to make their own calculations