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.