Young woman with head in hands

The clinical effectiveness and cost-effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED) study

No drugs are approved for treating people who have borderline personality disorder. In recent years, doctors have tried prescribing ‘clozapine’ and think that it may improve people’s mental health and reduce self-harm and impulsive behaviour. However, clozapine has serious side effects, including reductions in white blood cells, which are potentially life-threatening. This means that people prescribed clozapine need regular blood tests and other checks on their physical health.

What we planned

We planned to conduct the first ever clinical trial of clozapine to see if it helps improve the mental health of inpatients with borderline personality disorder. We aimed to recruit 222 people and randomise them to either clozapine or a placebo. The placebo was a capsule that looked the same as clozapine but did not contain any medication. We planned to follow up everyone for six months so that we could compare the mental health of people prescribed clozapine with those who took the placebo. 

What happened

We found it hard to recruit people to the study. Inpatients on general wards were usually not in hospital long enough to have the physical health checks they needed. Many patients and staff on secure units simply wanted to use clozapine rather than take part in the trial. In March 2020, we had to stop the trial because of COVID. Some hospitals gave us permission to restart recruitment again in autumn 2020. However, researchers were not allowed to visit the wards, and this made it even more difficult to continue the study. By February 2021, we had recruited 29 people. With funding running short, we decided to stop the study and learn what we could from the information we had collected.

What we found

Some patients and staff did not want to take part in the study because of concerns about side effects from clozapine, others wanted medication and were worried that people would be given a placebo.

It was very difficult to treat people admitted to general adult wards with clozapine because they were due to be discharged before they had the physical health checks that are needed.

Even though they weren’t told what they were taking, most people prescribed clozapine took it, but 6 out of 10 people prescribed placebo stopped it before their six-month follow-up assessment.

We found that the mental health of almost all people who took part in the study had improved after six months. The improvement in mental health among people who took clozapine was greater than that among people who took the placebo, but the study was too small for us to know if this was due to the medication that people were given.

We are grateful to all those who took part in the CALMED trial. Although not enough people were entered into the study for us to be able to properly test the effects of clozapine for inpatients with borderline personality disorder, we were able learn lessons about the challenges of conducting a trial like this. We hope that these lessons can be used to plan future studies aimed at improving the mental health of inpatients with borderline personality disorder.

If you would like to find out more about the CALMED trial, please read the findings here.