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Reports of research work funded by grants prior to 2015

University of Otago Wellington

Antipsychotic induced gastrointestinal hypomotility

S Every-Palmer
Department of Psychological Medicine

Our project investigates gastrointestinal hypomotility (“slow gut”) caused by antipsychotic medication, a common, important and poorly understood side effect spectrum that causes distress and even sudden death amongst those with serious mental illnesses.  Up to 50% of patients prescribed antipsychotics (especially those on clozapine) suffer chronic constipation as a side effect, reducing their quality of life. Some of these patients experience such profound gut motility problems that they develop obstruction which can lead to their bowel perforation.  In Australia and New Zealand dozens of mental health patients have died from these complications.

In 2014 we completed a pilot study (the first of its kind) investigating how long it took for food to pass through the gut (termed transit time) in antipsychotic-treated patients.  In normal healthy adults transit time is usually just over 24 hours.  We found some antipsychotics virtually paralysed the bowel.  For example, all subjects on clozapine had profoundly abnormal gut function, with average transit times being over four days.  Some of the patients had not passed any bowel motions for over a week, but had become so accustomed to this they did not perceive it as abnormal.  

These results clearly warranted further investigation, particularly to determine whether medications like laxatives are helpful in improving gut function and reducing the risk of serious side effects like obstruction and bowel perforation.  Surprisingly this has never been studied before, although antipsychotics are some of the most commonly prescribed medications in the world.  The principal investigator is currently doing a comprehensive review on this topic for the Cochrane Library and has failed to find any trials addressing management of this problem.

If our research does show that treating slow gut transit times is successful, we hope this might change the way people with psychotic disorders are managed, not just in New Zealand but internationally, with all patients starting on antipsychotics like clozapine being offered laxatives as protection against the universal and potentially serious “slow gut” side effects.  This would likely lead to improved health outcomes in this disadvantaged group of patients.

The WMRF partial grant validated the importance of the topic.  In order for the project to be viable (i.e. adequately powered) it has been necessary to obtain additional funding before commencing.  Although the WMRF provided money towards the first year costs, we did not want to start recruitment until we knew funding would be available for the second year (as ethically this would mean exposing participants to bowel motility studies for a project that would be potentially underpowered).  We have spent the last nine months making further research applications to other funding bodies.  We have also been collaborating with Massey University to borrow some of their equipment to reduce expenditure.

 We are pleased to advise that we have been successful in obtaining further funding including a partial grant from the Maurice and Phyllis Paykel trust and a grant-in-aide from the University of Otago which collectively mean the project is now viable and recruitment is about to start.

We have modified our bowel motility protocol due to some operational difficulties.  We planned to use radiopaque markers (ROMs) and nuclear medicine scintigraphy with egg pre-labelled with a technetium colloid in order to quantify bowel motility.  The scintigraphy investigations were to be conducted at the Nuclear Medicine Department of Wellington Public Hospital.  There were a number of logistical difficulties with this, particularly resourcing difficulties at the Nuclear Medicine Department, with a shortage of experienced staff meaning our research participants could not easily be accommodated.  This, combined with the time required and the radiation exposure to the patient has meant we modified our protocol to perform the bowel motility studies with a wireless motility capsule (WMC) obviating the need for both nuclear medicine and ROMs hence avoiding duplication of tests and radiation exposure.  This will yield better results and will be better tolerated by our participants.  The WMC is a vitamin-pill sized single use capsule that is easily swallowed by the participant.  It is an ambulatory, safe, minimally invasive and validated diagnostic modality that allows continuous assessment of intraluminal pH, temperature, and pressure during its transit through the gastrointestinal (GI) tract.  The technology allows for measurement of transit times in multiple regions of the upper and lower GI tract.

Recruitment for the antipsychotic induced hypomotility project will start in August 2015.  

Antipsychotic induced gastrointestinal hypomotility

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