It might seem that by calling your attention to this post on Dr. Doug Bremner's blog--
--I am being incredibly self-serving, as the post includes a nice plug for HOOKED, which Dr. Bremner has just begin to read. (Hey, better late than never. He's been busy writing his own book as you'll see from his blogsite.) However, read past that and you'll see a useful commentary on an article and editorial that recently showed up in Lancet (cited at end of this post; subscription required to access article).
The so-called first generation antipsychotic medications, of which one of the most widely known is probably haloperidol (Haldol), were reasonably effective in treating the symptoms of schizophrenia and other psychoses--indeed, the arrival of those medications in the 1950s was seen as the main reason why the inmates of the old state psychiatric hospitals could be let out into the community, though what really happened there is a whole different story. However, the doses required to effectively treat serious psychosis, and the life long nature of many psychoses, led to the major downside, the severe side effects resembling Parkinson's disease.
Along came the "second generation" antipsychotics, among which the best known is probably risperidone (Risperdal). The word on the street was that these drugs work as well as, or even better than, their first generation cousins, but are much kinder and gentler in terms of side effects--thus making them worth the high cost (the new kids on the block being brand name while the old guys had gone generic ages ago). The word on the street was dashed recently with revelations that meds like Risperdal were causing humongous weight gain and new onset diabetes among many psychiatric patients.
Leucht and colleagues from Munich set out to do a meta-analysis of all the available studies that compared first-and second-generation drugs directly, and summarized what they had found from 150 such studies. Tyrer and Kendall added a pithy editorial comment.
In typical British fashion, the editorialists do not mince words:
Stefan Leucht and colleagues [suggest] that what was seen as an advance 20 years ago—when a new generation of antipsychotic drugs with additional benefits and fewer adverse effects was introduced—is now, and only now, seen as a chimera that has passed spectacularly before our eyes before disappearing and leaving puzzlement and many questions in its wake.
Importantly, the second-generation drugs have no special atypical characteristics that separate them from the typical, or first-generation, antipsychotics. As a group they are no more efficacious, do not improve specific symptoms, have no clearly different side-effect profiles than the first-generation antipsychotics, and are less cost effective. The spurious invention of the atypicals can now be regarded as invention only, cleverly manipulated by the drug industry for marketing purposes and only now being exposed.
On present evidence from all sources it is difficult not to conclude that the trials of the second-generation antipsychotics seem to be driven more by marketing strategy than to clarify their role for clinicians and patients.
How, ask the editorialists, did the marketers accomplish this subterfuge? The meta-analysis by Leucht et al. shows that the major strategy was first, to always compare the newer drug to haloperidol, known to cause more Parkinsons-like symptoms than others; and second, to choose whenever possible the highest dose of haloperidol to maximize its side effects. (Strategies that Dr. Bremner kindly notes were discussed in HOOKED.)
What all of these authors agree on is that both first- and second-generation (so-called) antipsychotics are a motley crew of individual drugs. Instead of throwing them in wastebasket categories, the smart physician should be carefully distinguishing among them and choosing the right one for each individual patient based on benefits, side effects, and costs.
The tragedy here is that had any of this hot-shot science been invested in issues of clinical importance rather than used as marketing (recall that we are talking about 150 clinical trials, which is not exactly chopped liver), by now we would have a sizeable database on what drug works best for which type of patient, allowing the dedicated doc to choose based on decent evidence. Because the exercise was taken over by marketing hype from the get-go, we are more or less back to square one. "Old drugs bad, new (expensive) drugs good"--maybe an excellent marketing message, but lousy science.
Leucht S, Corves C, Arbter D, et al. Second-generation vs. first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 373:31-41, 2009.
Tyrer P, Kendall T. The spurious advance of antipsychotic drug therapy. Lancet 373:4-5, 2009.