Podcast: Drug treatments for constipation caused by antipsychotic medications

Antipsychotic medicines are widely used in mental health settings and there are several Cochrane Reviews of their potential benefits and harms. One of the adverse effects is constipation and a new Cochrane Review from January 2017 looks at some of the treatments for this. We asked the lead author, Susanna Every-Palmer from the Wellington School of Medicine in the University of Otago in New Zealand to tell us what they found.

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John: Hello, I'm John Hilton, editor of the Cochrane Editorial unit. Antipsychotic medicines are widely used in mental health settings and there are several Cochrane Reviews of their potential benefits and harms. One of the adverse effects is constipation and a new Cochrane Review from January 2017 looks at some of the treatments for this. We asked the lead author, Susanna Every-Palmer from the Wellington School of Medicine in the University of Otago in New Zealand to tell us what they found.

Susanna: Antipsychotic-related constipation is a common and serious adverse effect, especially for people taking clozapine. For every thousand patients treated with this drug, 300 to 600 will suffer constipation and at least four will develop serious gastrointestinal complications (such as paralytic ileus), from which at least one will die.
It’s important, therefore, to have effective and safe treatments for antipsychotic-related constipation and we did our Cochrane Review to look at the evidence on pharmacologic treatment. We defined pharmacological treatments broadly as laxatives and any other medicines that might be used to combat constipation in this population.
We found surprisingly little evidence. There were no eligible studies in the Western literature and the four potentially relevant studies were all published in China; and only two of these reported sufficient data to be included, giving a total sample of just 480 participants.
The included studies had Traditional Chinese Medicine, or TCM, as their primary focus, meaning that there are no robust, randomised trials of the common treatments for constipation, like fibre supplements, senna, docusate, lactulose, or macrogol, or of novel treatments such as linaclotide.
The two included studies were over ten years old, poorly reported, and we classified both as having a high risk of bias. They were also short, with one running for just 24 hours, and one for 17 days.
However, it is still worth thinking a little about their results. One study found that glycerol enema was less effective than TCM in promoting a bowel movement in constipated psychiatric inpatients, and the other study found mannitol to be more effective than rhubarb soda or phenolphthalein. We found no data for our other important outcomes such as the need for rescue medication, acceptability, leaving the study early, quality of life, serious adverse events, or economic costs.
Overall, we have to conclude that there is insufficient trial-based evidence to make specific recommendations about treating antipsychotic-related constipation. This is disappointing. It’s not an obscure adverse effect. It’s common, and particularly in the case of clozapine, potentially life-threatening. We hope that more studies will be done to address this massive evidence gap and that these will use a validated method of measuring constipation (such as the Rome criteria), last at least a month and consider medium- and long-term outcomes including serious outcomes. We also recommend looking to the evidence on the treatment of chronic constipation in the general population to help guide treatment choices.”

John: If you would like to read the current version of Susanna’s review and to watch for future updates should the much-needed trials get done, you can find it online. Just go to Cochrane Library dot com and search ‘antipsychotic-related constipation’.

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