Drugs News and Health Blog

Source: Before you take the pill (Doug Bremmer)

Spurious Advances in Antipsychotics, Indeed

An article from the Jan. 3 2009 issue of The Lancet used a meta analysis to show that so-called first generation antipsychotics (FGAs) and second generation antipsychotics (SGAs) are not that much different in terms of efficacy, safety, and side effect profiles. The purported superiority of SGAs for negative symptoms and fewer side effects for SGAs were primarily the results of comparator studies that put them up against high dose haloperidol.
I have been reading a book called Hooked: the Medical Profession and the Pharmaceutical Industry by Howard Brody, MD PhD, of the University of Texas, Galveston, which I highly recommend as an interesting book that adds a lot even for those of you who feel you are “read out” on this topic, and this episode of comparing new drugs to old drugs given at doses that cause more side effects without providing more efficacy (which is stacking the deck in favor of the new drugs) is a pharmaceutical industry tactic that he identifies, although this is the first time we have heard of it as applied to antipsychotic “life saving drugs”.
Psychiatrists moved en masse from the FGAs to the SGAs largely because of concerns about tardive dyskinesia, extra pyramidal side effects, and what may have been a misguided belief that these drugs worked better, fueled by pharmaceutical marketing. As the paper shows, most studies in the literature were found to be using high dose haloperidol (>7.5 mg/day) (Haldol) as the comparison drug, which biased the trials in favor of showing a better side effect profile for the newer drugs. When studies using lower potency first generation drugs were focused on, the differences in safety and efficacy were considerably diminished. Specifically, the SGA drugs as a whole were not seen to be specifically better for negative symptoms of schizophrenia, which does not support marketing claims to the contrary. The drugs that were better for negative symptoms were also equally better for positive symptoms and depression. Although clozapine, olanzapine, and risperidone were marginally better for extra pyramidal side effects, which is largely why psychiatrists moved so heavily into SGAs in the first place, the effects were not large, and there were no significant differences for the other SGAs. The only SGAs that were shown to be better for psychotic symptoms than low dose FGAs were amisulpride (Solian, Sultopride), clozapine (Clozaril), olanzapine (Zyprexa) and risperidone (Risperdal). These drugs, however, caused more weight gain than haloperidol (but not low potency FGAs). Only Amisulpride and sertindole (Serlect) were better for quality of life. Aripiprazole (Abilify) was only better for depression and quetiapine (Seroquel) was better for positive symptoms and depression. Sertindole (Serlect), ziprasidone (Geodon), and zotepine (Zoleptil) were not better for any symptom area.
The recent CATIE study compared SGAs to the FGA perphenazine (Trilafon), and found that most of them were not better for efficacy or side effects, only olanzapine had a longer time to discontinuation (the primary outcome) and clozapine was better for symptoms. However, clozapine has bothersome blood monitoring requirements because of the risk of aplastic anemia, and olanzapine has some worrisome diabetes risks. What was most amazing about the CATIE study, however, was the fact that half of people stopped taking their meds after a couple of months, which indicates that people feel really lousy on these drugs.
The article was accompanied by and editorial by Turner and Horton entitled “The Spurious Advance of Antipsychotic Therapy” in which the authors said that psychiatrists had been “beguiled” (presumably by the pharmaceutical industry) into believing that the SGAs were superior (a point highlighted by others like Vera Sharav of the Alliance for Human Research Protection (AHRP). Although I wouldn’t agree with the emphasis that there isno difference between these drugs, it is true that the safety and efficacy of these drugs have been greatly distorted, that we should stop using the distinction of SGA-FGA or talking about unique profiles of “atypicals”. In addition, It is unclear if the extra cost of these drugs justifies their use when there is an increased risk of obesity and diabetes with not that great of an advantage for extra pyramidal side effects. Certainly for the drugs not better than low potency FGAs there is not.
Guess we got duped by pharma. Yet again.
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Mayor mortalidad en enfermos de Alzheimer que toman antipsicoticos

La revista The Lancet Neurology publicó un amplio estudio en el que se ha encontrado un aumento de la mortalidad en relación con la toma de antipsicóticos en pacientes con enfermedad de Alzheimer.
Los datos de varios estudios controlados con placebo han llevado a la preocupación acerca de una mayor mortalidad en pacientes con enfermedad de Alzheimer a los que se les han prescrito antipsicóticos. Sin embargo, tales estudios han sido de 12 semanas de duración, y no se conocían datos de mortalidad en ensayos con placebo a largo plazo.
Los participantes, 165 enfermos de Alzheimer institucionalizados, fueron asignados aleatoriamente entre octubre de 2001 y diciembre de 2004 para continuar recibiendo su tratamiento antipsicótico durante 12 meses, o para recibir placebo en su lugar. El primer dato de salida fue la mortalidad a los 12 meses, llevándose a continuación un seguimiento telefónico para establecer qué sujetos continuaban con vida 24 meses más tarde del reclutamiento del último participante (entre 24 y 54 meses de rango). Las causas de muerte fueron obtenidas de los certificados de defunción.
Se encontró una reducción de la supervivencia en los pacientes que continuaron tomando antipsicóticos en relación con los que tomaron placebo. La probabilidad acumulada de supervivencia durante los 12 primeros meses fue del 70% para los sujetos que tomaron antipsicóticos, frente al 77% para los sujetos a los que se les administró placebo en su lugar.
Las diferencias fueron más pronunciadas entre el grupo con antipsicóticos y el grupo con placebo durante los periodos de seguimiento más allá de los 12 meses, siendo muy evidentes en puntos de corte específicos: 46% frente a 71% a los 24 meses, y 30% frente a 59% a los 36 meses, respectivamente.
En base a estos resultados, los autores interpretan que:
«Existe un riesgo aumentado de mortalidad en pacientes con enfermedad de Alzheimer que están tomando medicación antipsicótica; estos resultados resaltan aún más la necesidad de buscar alternativas menos peligrosas para el tratamiento a largo plazo de los síntomas neuropsiquiátricos en estos pacientes».
Referencia bibliográfica: Clive Ballard, Maria Luisa Hanney, Megan Theodoulou, Simon Douglas, Rupert McShane, Katja Kossakowski, Randeep Gill, Edmund Juszczak, Ly-Mee Yu, Robin Jacoby, for the DART-AD investigators. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. The Lancet Neurology 2009; Digital Object Identifier (DOI):10.1016/S1474-4422(08)70295-3.