Peter B. Jones, MD, PhD, of the department of psychiatry at the University of Cambridge, the lead researcher on the study, summarized the attitude of clinicians as "beguiled" by the appeal of atypicals.
The UK study involved 227 persons aged 18 to 64 with DSM-IV schizophrenia and related disorders whose psychiatrists had elected to change their treatment because of inadequate clinical response or intolerance of their current medication. They were randomized into 2 groups, one receiving an older antipsychotic and the other an SGA. The patients' own psychiatrists selected one of the agents designated for the appropriate treatment group.
FGAs in the study were chlorpromazine(Drug information on chlorpromazine) hydrochloride (Thorazine), flupenthixol (Fluanxol), haloperidol (Haldol), loxapine (Loxitane), methotrimeprazine (Nozinan), sulpiride (Dolmatil, Sulpitil), trifluoperazine(Drug information on trifluoperazine) hydrochloride (Stelazine), zuclopenthixol(Drug information on zuclopenthixol) (Clopixol), and the depot preparations of fluphenazine(Drug information on fluphenazine) (Prolixin, others), flupentixol(Drug information on flupentixol) (Depixol), haloperidol, pipotiazine (Piportil), and zuclopenthixol. Two other drugs, thioridazine(Drug information on thioridazine) hydrochloride and droperidol(Drug information on droperidol), had been included in the trial protocol but were dropped because they were withdrawn from licensed use.
SGAs used in the trial were risperidone (Risperdol), olanzapine(Drug information on olanzapine) (Zyprexa), amisulpride(Drug information on amisulpride) (Solian), zotepine(Drug information on zotepine) (Zoleptil), and quetiapine(Drug information on quetiapine) (Seroquel). Another atypical, ziprasidone(Drug information on ziprasidone), was not included because it has not been licensed in England. Not all of the drugs used in the trial are available in the United States.
The patients were evaluated using the Quality of Life Scale (QLS) at baseline and again at 12, 26, and 52 weeks. Secondary outcome measures included the Positive and Negative Syndrome Scale (PANSS); Calgary Depression Scale; the Drug Attitude Inventory and a 7-point drug adherence scale; Global Assessment of Functioning Scale; and several adverse effects scales to monitor for negative reactions.
In the end, "participants in the FGA arm tended to have greater improvements in QLS and symptom measures than those in the SGA arm, suggesting that the failure to find an advantage for SGAs was not due to the sample simply being too small. We emphasize that we do not present a null result; the hypothesis that SGAs are superior was clearly rejected," the researchers wrote.
Manufacturers of the newer drugs were quick to respond to the study. "I see at least design flaws with the study," said James Minnick, a spokesman for AstraZeneca, which makes the SGA Seroquel (quetiapine). "Patients were randomized to either first-generation or second-generation treatment, but the choice of medication wasn't random. Patients weren't blinded to what they were taking. The other point might be that every medication is different, and by lumping all second-generation drugs together and inferring they are the same, their unique attributes are undermined."
But Robert W. Baker, MD, group director of global product safety in therapeutic areas for Eli Lilly and Company, put a more positive face on the results. "It's valuable and interesting information for clinicians," he said. "It is useful if they . . . [learn] from this study and the vast existing literature on antipsychotics. It reinforces the notion that because individual drugs and patients differ from each other, clinicians can help their patients best if they are well informed and aggressively pursue the best choice." Eli Lilly's Zyprexa (olanzapine) was one of the SGAs included in the study and fared reasonably well in terms of acceptance. At the end of the study, 74% of the SGA patients for whom olanzapine had been prescribed were still taking the drug.