Do the New Antipsychotics Make A Difference?

Major study published in the British Medical Journal  on the effectiveness of treating schizophrenia with antipsychotic drugs.

Although most individuals with psychosis show a moderate to substantial reduction in their positive symptoms after treatment with antipsychotic drugs, about 30% of patients do not respond to psychopharmacology. The negative symptoms of schizophrenia are even less responsive to drug treatment. Once an individual is in remission, antipsychotic drugs substantially reduce the risk of relapse. During one year, 55% of those on placebo have a relapse compared with 20-25% of those on antipsychotic drugs.

The greatest limitation of treatment with traditional antipsychotic drugs has been their side effects. In particular, people with schizophrenia have had to tolerate disabling and distressing extrapyramidal side effects such as parkinsonism, akathisia (restlessness in the legs and body), acute dystonia, and tardive dyskinesia (involuntary movements, often of the tongue and face but also of the fingers, hands, legs, and trunk).

The recommended doses for acute and maintenance treatment with traditional antipsychotics can be found in guidelines such as those published by the Patient Outcomes Research Team. [4] Several new antipsychotic drugs have been introduced recently. Of these, risperidone (Risperdal), olanzapine (Zyprexa), and clozapine (Clozaril) are available in most countries. At the time of writing, aripiprazole (Abilify) has been approved in the U.S., quetiapine (Seroquel) was available in some countries but sertindole has been withdrawn pending review of data on cardiac safety. Ziprasidone (Geodon) is are available in most countries. At the time of writing, awaiting approval in many countries, but may be introduced in the next year or so. These drugs are sometimes called atypical antipsychotics.

There is a substantial body of evidence that shows that the new antipsychotic drugs are effective in treating positive symptoms.[9] Data from trials and clinical experience also suggest that they are effective in reducing the risk of relapse during maintenance treatment, although the evidence is less extensive. In the past it was commonly thought that all traditional antipsychotics were equally effective.[10] A recently published Cochrane review comparing clozapine with traditional antipsychotics has shown that clozapine has greater clinical efficacy than traditional antipsychotics.[11] It has been claimed that some of the other new antipsychotics have statistically significant advantages on various measures of clinical outcome when compared with traditional antipsychotics; however, it remains to be seen whether these differences are clinically relevant in daily practice. There is evidence to suggest that patients on the new antipsychotic drugs have superior performance on neurocognitive measures (for example, working memory) compared with patients on traditional antipsychotics.[12 13]

The table summarises selected data on the efficacy and side effects of the new antipsychotics. Clozapine, olanzapine, and quetiapine have a wide range of receptor affinities and the other products have more selective dopamine and serotonergic properties. Because of the increased risk of agranulocytosis associated with clozapine, it should not be the first choice treatment. Updated sources of evidence based recommendations should be consulted regularly. Some of these sources are given in the box.

The greatest limitation of treatment with traditional antipsychotic drugs has been their side effects. In particular, people with schizophrenia have had to tolerate disabling and distressing extrapyramidal side effects such as parkinsonism, akathisia (restlessness in the legs and body), acute dystonia, and tardive dyskinesia (involuntary movements, often of the tongue and face but also of the fingers, hands, legs, and trunk).

The recommended doses for acute and maintenance treatment with traditional antipsychotics can be found in guidelines such as those published by the Patient Outcomes Research Team.[4] Several new antipsychotic drugs have been introduced recently. Of these, risperidone, olanzapine, and clozapine are available in most countries. At the time of writing quetiapine was available in some countries but sertindole has been withdrawn pending review of data on cardiac safety. Ziprasidone is awaiting approval in many countries, but may be introduced in the next year or so. These drugs are sometimes called atypical antipsychotics.

There is a substantial body of evidence that shows that the new antipsychotic drugs are effective in treating positive symptoms.[9] Data from trials and clinical experience also suggest that they are effective in reducing the risk of relapse during maintenance treatment, although the evidence is less extensive. In the past it was commonly thought that all traditional antipsychotics were equally effective.[10] A recently published Cochrane review comparing clozapine with traditional antipsychotics has shown that clozapine has greater clinical efficacy than traditional antipsychotics.[11] It has been claimed that some of the other new antipsychotics have statistically significant advantages on various measures of clinical outcome when compared with traditional antipsychotics; however, it remains to be seen whether these differences are clinically relevant in daily practice. There is evidence to suggest that patients on the new antipsychotic drugs have superior performance on neurocognitive measures (for example, working memory) compared with patients on traditional antipsychotics.[12 13]

The table summarises selected data on the efficacy and side effects of the new antipsychotics. Clozapine, olanzapine, and quetiapine have a wide range of receptor affinities and the other products have more selective dopamine and serotonergic properties. Because of the increased risk of agranulocytosis associated with clozapine, it should not be the first choice treatment. Updated sources of evidence based recommendations should be consulted regularly. Some of these sources are given in the box.