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DNA Methylation in Type 2 Diabetes and Weight loss


Reports of research work funded by grants prior to 2016

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.

It took us a while to obtain sufficient funding to start the study.  The equipment necessary to conduct wireless motility capsule studies (WMC) is unfortunately expensive, with the cost per study exceeding $1000.  However there is no alternative technique that could provide similar data without radiation exposure.  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.

We also received additional funding from the Maurice and Phyllis Paykel trust and a grant-in-aide from the University of Otago which collectively meant the project became viable in the middle of last year.  We are also grateful to Massey University for lending us some of the equipment.

We began recruiting in October 2015.  To date we have performed 12 whole-of-gut motility studies in clozapine treated patients using a WMC.

The studies have been successful and well tolerated by all participants.  We are continuing to recruit at a slow and steady rate (this takes time as the possible pool of participants is small; they must be mentally stable inpatients residing on campus, competent to consent and having achieved a constant clozapine dose with the appropriate leave).  We will have recruited 15-20 participants by the end of 2016, which is when recruitment will cease.  At this stage there is every indication that the study will be adequately powered and that the results will change the way we think about this important topic


DNA Methylation in Type 2 Diabetes and Weight loss

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