Understanding the physical harm of taking more than one antipsychotic drug for schizophrenia

Schizophrenia is a serious mental illness that affects about 1 per cent of people. The most common treatment is a type of drug called an antipsychotic. Many patients are prescribed more than one at a time, even though experts recommend that only one should be taken at a time. There is no clear evidence that taking more than one at a time is more effective.

People with schizophrenia die about 20 years earlier than those without a serious mental illness, partly because they are more likely to have serious health problems such as obesity, diabetes, high blood pressure and high cholesterol. All of these increase the risk of having a heart attack or stroke. People may be more likely to have these problems if they take more than one antipsychotic over a long time, although we don’t have firm evidence about this.

Project aims

We want to find out whether taking more than one antipsychotic drug increases the chance of having serious physical health problems.

What we did

The project has two parts:

  • We looked at reviews of existing research on the association between taking more than one antipsychotic and high blood pressure, diabetes or high blood fat levels
  • We are analysing routine data on a large group of middle-aged people with schizophrenia collected from GP surgeries, to find out how many anti-psychotic drugs they are prescribed, and if being prescribed more than one gives them a higher risk of health problems

What we found and what this means

We found 12 systematic reviews of existing research, but the evidence they provided was low quality, so the findings weren’t very reliable.

Most of the reviews included clozapine, a commonly prescribed antipsychotic which is used when a patient doesn’t respond to other antipsychotics.

There was some indication that drug combinations with aripiprazole can protect against diabetes and high blood fat levels, compared to combinations without aripiprazole or single drug therapy. But we can’t be sure because the data was limited and from just a few small studies.  The only evidence on high blood pressure was from one low quality review, which said taking more than one antipsychotic drug didn’t increase the risk of high blood pressure.

Most people with schizophrenia are treated by their GP, with only severe cases treated in hospitals or specialist centres. None of the reviews separated results for patients treated by their GP from those treated in hospital.

With the existing evidence, we can’t be sure if taking more than one antipsychotic drug is effective or safe for most schizophrenia patients.

We are now working on the analysis of the routine GP data.

What next?

We will use the routine data to look at the relationship between more than one antipsychotic and high blood pressure, high blood fat levels and diabetes. We have ethical approval for this work and have started the analysis. We will also investigate whether some combinations of antipsychotic drugs are more harmful than others.

We will develop a long-term study of patients in the care of GPs to understand the risk of getting diabetes, high blood pressure and high blood fat levels when taking more than one antipsychotic drug.

We also need to find out whether using aripiprazole in combination with other antipsychotics could have benefits.

Links and downloads

Lead collaborators

CLAHRC West staff

profile picture Alison Richards

Alison Richards

Jelena Savovic

Dr Jelena Savović

  • Senior Research Fellow in Evidence Synthesis
  • Evidence
  • Team Lead

Dr Paul Moran

Dr Sharea Ijaz

Dr Theresa Redaniel

Partners on this project

University of Bristol

The University of Bristol is internationally renowned and one of the very best in the UK, due to its outstanding teaching and research, its superb facilities and highly talented students and staff. Its students thrive in a rich academic environment which is informed by world-leading research. It hosts the Elizabeth Blackwell Institute for Health Research.