Do new drugs work better than old for treating schizophrenia?

The challenge

Pharmacological treatment of schizophrenia began in the early 1950s with the discovery that chlorpromazine had antipsychotic properties. Since then, conventional or typical antipsychotic drugs have formed the pillar of both acute and long-term treatment for schizophrenia, and have been invariably used as a  first line of therapy.

Then ‘atypical’ antipsychotics were introduced - a new class of drugs with a lower risk of side effects and, in the case of clozapine, better outcomes. These second-generation drugs appeared to have important advantages over their conventional predecessors, including better effectiveness for a variety of symptoms, and improved tolerability.The cost of these new drugs however was 20 - 30 times that of conventional drugs and little scientific evidence was available to support their superiority.


Man with mental health issues

What we did

To enable better prescribing decisions, a 4-centre, randomised, controlled trial was conducted. It aimed to evaluate the relative effectiveness of the new drugs compared to conventional drugs and to clozapine in a sample of 702.

The patient population comprised people for whom a change in antipsychotic drug treatment was being considered, because of intolerance or insufficient clinical improvement, and for whom a choice between a first-generation antipsychotic and a second-generation antipsychotic (other than clozapine) was relevant.

The trial set out to demonstrate important differences in quality of life and other outcomes after one year, assess value for money and identify cost-effective management strategies.



What we found

The results of the study showed that atypical antipsychotic drugs offered no clear advantage over the older, typical drugs that had been used for the treatment of schizophrenia.

In people with schizophrenia whose medication was changed to clozapine, rather than new atypical drugs due to treatment resistance, there was a significant advantage in terms of symptoms but not quality of life and with increased associated costs of care.




As a result of the CUtLASS findings, NICE changed its recommendation from using an atypical antipsychotic as first-line treatment to discussing with the patient which drug should be used, with no mention of whether or not that should be typical or atypical.

This in turn could lead to more careful prescribing of antipsychotics, with more consideration of side effects and quality of life.