Clozapine deaths cause concern
It was a Thursday in autumn when Daniel Warburton ate dinner with his parents, Maureen and Alan Warburton, as he did every week.
Daniel, who lived with schizophrenia, complained he felt a bit sick, but put it down to extra exercise.
On the Saturday, it was Alan Warburton who found Daniel, 37, lying on the porch of his Christchurch flat, television still going in the background.
‘‘I found him outside looking up at the sky. They’re not sure if he died on the Friday night or early hours of Saturday. But that was it,’’ Warburton said.
‘‘We didn’t realise – Daniel didn’t realise that he was on this train that was going to end for him.’’
A coroner’s report has determined Daniel’s death was caused by a condition called clozapineinduced gastrointestinal hypomotility (CIGH) – also known as slow-gut.
Data on antipsychotic drug clozapine found Daniel was one of 13 New Zealanders to die from the gut anomaly, prompting both Alan and Wellington researchers to call on drug manufacturing companies to take urgent action.
The condition can result in severe constipation, bowel obstruction, or death, said researchers from the University of Otago, Wellington, and Capital & Coast District Health Board.
Clozapine is one of the main treatments for schizophrenia, and works better than any other medication in about one third of people.
Researchers analysed all 160 reported cases of serious clozapineinduced ‘‘slow-gut’’ submitted to New Zealand and Australian
"People lose sight of what to watch out for." Alan Warburton
agencies over a 22-year period.
At least 29 of these patients died. Serious slow-gut reactions affected users of all ages, from a 17-year-old boy to 73-year-old man.
‘‘Despite a number of recent coroner’s cases looking at this sideeffect spectrum, with recommendations for better information and monitoring, we are yet to see action,’’ co-author Professor Pete Ellis, of the university’s Psychological Medicine Department, said.
Warburton said Daniel took clozapine for about 16 years, and if the family were told anything ‘‘it was lost in the vapour of time’’.
‘‘The key thing for us is making people aware of the risks of this drug, and it needs to be ongoing. People lose sight of what to watch out for.
‘‘We just thought he was unwell because he had been doing too much exercise. We didn’t see it.’’
While the researchers did not want people to stop taking the drug out of fear, they were worried that the message had not been getting across.
Lead author Dr Susanna EveryPalmer said: ‘‘Official drug safety information in all countries underestimated the prevalence of clozapine-induced slow gut almost 40-fold and provided almost no information about the range of effects this has.
‘‘We think serious harm from clozapine-related slow-gut is preventable, but ... this is not an area to which researchers have been paying much attention.’’
Every-Palmer and Ellis compared the rate of serious clozapinerelated gastrointestinal complications with those in official drug safety sheets issued in New Zealand, Australia, Britain and the United States. ‘‘While Medsafe has issued a number of prescriber updates on this issue, the manufacturers’ official drug safety data sheets are completely out of date,’’ Every-Palmer said.
Earlier studies by the same team measured the frequency and extent to which clozapine affected gut function, finding that clozapine slowed the gut in 80 per cent of users. Giving laxatives improved gut motility significantly for people taking clozapine and reduced the chances of serious harm such as bowel obstruction.
Ellis said drug regulators such as the FDA, Medsafe and the MHRA in Britain need to ensure manufacturers keep clozapine data sheets up to date.