Why is clozapine different from other antipsychotics?

Professor David Taylor: Clozapine is an unusual medication, it is unusually effective. It is effective where other medications haven’t worked. It’s also unusual in its range and sometimes severity of its adverse effects. It causes a great many adverse effects, some of which are potentially fatal.

The most well-known of these is the effect on white blood cells, where it can cause them to disappear almost completely, which can be life-threatening, but it also causes a range of other adverse effects, on the heart, it affects saliva production, it causes constipation.

We found clozapine by accident. It was synthesised in 1959, originally designed as an antidepressant, found not to be an antidepressant, then it was moved on to trials in schizophrenia, it was found to be effective in schizophrenia. But because it didn’t cause movement disorders, people were suspicious about its efficacy, because in the 1960s, antipsychotics were given to people until they developed movement disorder and then that was felt to be the right dose to be on. With clozapine, you never get movement disorder, there was a lack of confidence about it. By the time people were gaining confidence with it in the 1970s, it was found to have been responsible for a number of deaths in Finland, through this effect on white blood cells, agranulocytosis, so it was withdrawn and reintroduced, having had its superior effects established during the 1980s and 1990s.

So it’s a unique medication, it’s extremely helpful in treating people who don’t respond to the medication. But it’s got a wide range of adverse effects and in an ideal world, we’d find a drug which is as effective as clozapine but without the side effects.

You’re monitored on clozapine because of the effect on the white blood cells. So for 18 weeks you have to have a blood count every week, and then up to a year, it’s every 2 weeks and then after a year it’s every month. In other countries it is different, in the USA, for example, you have to have weekly tests throughout the treatment period.