The common distinction between first- and second-generation antipsychotics has no scientific basis and should be dropped, according toa paper in The Lancet. A meta-analysis of 150 double-blind studies found little evidence that newer, so-called atypical antipsychotics are more effective than older drugs for symptoms of schizophrenia, MedPage Today writes.
The researchers also found that, although newer drugs induced fewer extrapyramidal effects (including tremor, slurred speech, restlessness, movement disorders, among other things) than Haldol, which is also known as haloperidol, this did not occur when compared with low-potency first-generation agents.
"Second-generation antipsychotic drugs differ in many properties" - including structure and mode of action as well as clinical effects - "and are not a homogeneous class," the researchers concluded. "Improper generalization creates confusion and, as a result, the classification (of first- versus second-generation agents) might be abandoned."
In an accompanying editorial, two British researchers went further, calling the notion that newer agents are more effective or safer than older drugs "spurious." "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," wrote Peter Tyrer of Imperial College in London and Tim Kendall of the National Collaborating Centre for Mental Health in London.
Both groups of researchers emphasized the findings do not mean that all antipsychotics are alike. Instead, they wrote "this meta-analysis provides data that clinicians could use for individualized treatment of patients with schizophrenia based on efficacy, side-effects, and cost of antipsychotic drugs."
In their analysis, for each efficacy and adverse-effect outcome they studied - overall symptoms, positive symptoms, negative symptoms, depression, extrapyramidal effects, weight gain, and sedation -- there was no clear pattern favoring newer over older drugs. Although they did find that four second-generation agents - Clozaril, Zyprexa, Risperdal and Solian, which is not approved in the US - were significantly more effective than older drugs.
The researchers wrote their findings differed from some earlier meta-analyses partly because they excluded open-label studies that "systematically favored second-generation drugs."
More than half the studies they did include had a different type of bias - Haldol was used as the comparative drug, according to Tyrer and Kendall. And this has a high rate of extrapyramidal effects compared with other first-generation drugs. The result, they suggested, was to make the side effect profile of the newer drugse look better than if other comparators had been tested instead.
The researchers said that most of the second-generation drugs "have not been shown to be better than low-potency first-generation antipsychotic drugs (for extrapyramidal effects), and we noted a robust superiority based on more than two studies only for" Clozaril.
Weight gain is more of an issue for second- than first-generation drugs, they found. In studies using Haldol as the comparator, Abilify and Geodon did not lead to more weight gain. There was no difference in weight gain between any second-generation drug and other older agents, they found. For sedation, no clear pattern emerged to separate first- from second-generation agents.
Many of the results of the meta-analysis echoed those of the prospective CATIE study, in which three newer agents were compared with perphenazine. The researchers wrote that the use of a comparator other than haloperidol in the CATIE trial was a major strength and should be repeated in future studies.
The National Institute of Mental Health funded the analysis. Stefan Leucht reported relationships with Sanofi-Aventis, Bristol-Myers Squibb, Lilly, Johnson & Johnsons' Janssen, Lundbeck, and Pfizer. Other study authors reported no potential conflicts of interest. Kendall reported involvement in an ongoing update of the schizophrenia guideline for the UK' National Institute for Health and Clinical Excellence. Tyrer reported no potential conflicts of interest.