Classification Of So-Called First Generation And Second Generation Antipsychotic Drugs Should Be Abandoned

Main Category: Schizophrenia
Also Included In: Psychology / Psychiatry;  Mental Health;  Pharmacy / Pharmacist
Article Date: 05 Dec 2008 - 5:00 PDT

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A meta-analysis of randomized controlled trials into the effects of antipsychotic drugs has found important differences between individual drugs, which are blurred by classification of 'first' or 'second' generation. Authors of an Article and an accompanying Comment, published Online first and in an upcoming edition of The Lancet, call for the classification to be abandoned.

Dr Stefan Leucht, Clinic and Polyclinic for Psychiatry and Psychotherapy, Technische Universität München, Germany, and Dr John Davis, University of Illinois Chicago, USA and colleagues compare nine second-generation antipsychotic drugs with first-generation drugs for overall efficacy (main outcome), positive, negative, and depressive symptoms, relapse, quality of life, extra-pyramidal side-effects*, weight gain, and sedation.

The meta-analysis included 150 studies and over 21,000 participants, and the analysis showed that four second generation drugs (amisulpride, clozapine, olanzapine, risperidone) were better than first generation drugs for overall efficacy, with small to medium sized differences. The other second generation drugs were not better. When compared with the high-potency first generation drug haloperidol (even at low doses), second generation drugs induced fewer extra-pyramidal side effects; but only a few second generation drugs were shown to induce fewer of these side effects when compared with lower-potency first generation drugs. With the exception of aripiprazole and and ziprasidone, second generation antipsychotic drugs induced more weight gain, in various degrees, than did haloperidol, but not than low-potency first generation drugs.

The authors conclude: "Because the second-generation antipsychotic drugs differ in many properties, including efficacy, side-effects, cost (some are now generic), and pharmacology (amisulpride is not a serotonin receptor blocker), they do not form a homogeneous class and neither do first generation antipsychotic drugs. Improper generalisation creates confusion and as a result the classification might be abandoned.

"This meta-analysis provides data that clinicians could use for individualised treatment of patients with schizophrenia based on efficacy, side-effects, and cost of antipsychotic drugs".

In the accompanying Comment, Professor Peter Tyrer, Department of Psychological Medicine, Imperial College London, UK, and Dr Tim Kendall of the National Collaborating Centre for Mental Health, Royal College of Psychiatrists' Research Unit, London, UK, say: "Individual responses vary, and so a range of drugs is needed for good clinical practice. So where should we go now? First, the time has come to abandon the terms first-generation and second-generation antipsychotics, as they do not merit this distinction. The only second-generation antipsychotic that is obviously better than other drugs in resistant schizophrenia is clozapine, and this is a very old drug indeed. Second, clinicians must remember to keep the benefit - risk ratio of each antipsychotic drug in constant perspective because all are associated in different ways with serious adverse effects, which should be important outcome measures. Finally, it is prudent to remember that although science rules during a drug's development, the market usurps control once the drug is released for care of patients."

*extra-pyramidal side-effects are those that resemble Parkinson's disease, eg, tremor and shuffling gait.

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Tony Kirby
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