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39 results

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  • Clozapine-induced gastrointestinal hypomotility: UK pharmacovigilance reports, 2018–2022

  • Robert James Flanagan, Simon Alfred Handley, Charlotte James, Lilly Wells, Susanna Every-Palmer
  • Journal:
    BJPsych Open / Volume 11 / Issue 3 / May 2025
    Published online by Cambridge University Press:
    31 March 2025, e79
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  • Background

    Clozapine-induced gastrointestinal hypomotility (CIGH) can cause constipation, which may progress to ileus, intestinal perforation and other life-threatening conditions. There were at least 527 unique cases of harmful CIGH (172 deaths) assessed by strict criteria in the UK, 1992–2017.

    Aims

    To assess the impact of strengthened warnings about the risks of CIGH, such as those issued by the UK Medicines and Healthcare products Regulatory Agency (MHRA) (2017) and the US Food and Drug Administration (2020), on reports of harmful CIGH in the UK.

    Method

    We audited UK MHRA Yellow Card reports recorded as clozapine-related gastrointestinal disorders, 2018–end 2022.

    Results

    Of 335 unique reports (36 fatal, 26 male) that met initial CIGH criteria, there were 129 (22 fatal, 18 male) that met the final CIGH inclusion criteria. Reports of non-fatal CIGH (final criteria) averaged 26 per year (15 in 2022). Deaths averaged four per year (two in 2022). Where data were available the greatest proportion of deaths occurred after 10–14 years of clozapine treatment.

    Conclusions

    Publicity aimed at raising awareness of the problem posed by CIGH has been associated with a reduction in harmful CIGH as reported to the UK MHRA since 2017. Continued vigilance is needed to reduce risk. Stopping smoking may pose a particular risk and should be monitored carefully.

  • Opioid antagonists: clinical utility, pharmacology, safety, and tolerability

  • Roger S. McIntyre, Marni E. Harris, Mark S. Todtenkopf, Sarah Akerman, Joshua Burgett
  • Journal:
    CNS Spectrums / Volume 29 / Issue 6 / December 2024
    Published online by Cambridge University Press:
    25 November 2024, pp. 542-548
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  • Opioid antagonists block opioid receptors, a mechanism associated with utility in several therapeutic indications. Here, we review the sites of action, clinical uses, pharmacology, and general safety profiles of US Food and Drug Administration (FDA)-approved opioid antagonists. A review of the literature and product labels of opioid antagonists was conducted. The unique clinical uses of approved opioid antagonists are related to their ability to block opioid receptors centrally and/or peripherally. Centrally acting opioid antagonists treat opioid and alcohol use disorders (AUDs) and reverse opioid overdose. Because the opioid system influences weight and metabolism, one opioid antagonist combination product is approved for chronic weight management; another, approved for adults with schizophrenia or bipolar I disorder, mitigates olanzapine-associated weight gain. Peripherally acting opioid antagonists are approved for opioid-induced constipation; another accelerates gastrointestinal recovery after bowel surgery. Opioid antagonists are generally well tolerated; they are not associated with physiologic dependence or abuse. However, opioid antagonists can precipitate acute opioid withdrawal in patients using or undergoing withdrawal from opioid agonists. Likewise, their use can confer a risk for opioid overdose if attempts are made to overcome opioid antagonist blockade of opioid receptors via the intake of additional opioids. Opioid receptor antagonists have diverse therapeutic benefits based on their respective pharmacology and sites of action; understanding their respective nuances facilitates the safe and effective use of these agents.

  • Dietary fibre intakes of two cohorts of New Zealand adults with and without constipation

  • H.M. Ng, J. Maggo, C. Wall, S. Bayer, N.C. Roy, R. Gearry
  • Journal:
    Proceedings of the Nutrition Society / Volume 83 / Issue OCE1 / April 2024
    Published online by Cambridge University Press:
    07 May 2024, E72
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  • Adequate dietary fibre (DF) intake is recommended to relieve constipation and improve gut health(1). It is often assumed that individuals with constipation have relatively low DF intake and do not meet the recommended adequate intake of 25 g and 30 g for females and males, respectively. The 2008/09 New Zealand Adult Nutrition Survey confirmed that the mean DF was 17.9 grams (g) per day for females and 22.8 g per day for males, which was well below the recommended adequate intake(2). With the continuous shift of dietary patterns over time, we sought to compare the current usual DF intake of two cohorts of New Zealand adults: those who have constipation with those without constipation but with relatively low DF intake. We report baseline dietary data from two randomised controlled dietary studies (Kiwifruit Ingestion to Normalise Gut Symptoms (KINGS) (ACTRN12621000621819) and Bread Related Effects on microbiAl Distribution (BREAD) (ACTRN12622000884707)) conducted in Christchurch, New Zealand in 2021 and 2022, respectively. The KINGS study included adults with either functional constipation or constipation-predominant irritable bowel syndrome to consume either two green kiwifruit or maltodextrin for four weeks. The BREAD study is a crossover study and included healthy adults without constipation but with relatively low DF intake (<18 g for females, <22 g for males) to consume two types of bread with different DF content, each bread for four weeks separated by a two-week washout period. All participants completed a non-consecutive three-day food diary at baseline. Dietary data were entered into FoodWorks Online Professional (Xyris Software Australia, 2021) to assess mean daily DF intake. Fifty-six adults from the KINGS study (n = 48 females, n= 8 males; mean age ± standard deviation: 42.8 ± 12.6 years) and BREAD study (n = 33 females, n= 23 males; mean age: 40.4 ± 13.4 years) completed a baseline food diary. In the KINGS study, females with constipation had a daily mean DF intake of 25.0 ± 9.4 g whilst male participants consumed 26.9 ± 5.0 g per day. In the BREAD study, females without constipation had a mean daily DF intake of 19.4 ± 5.8 g, whereas males had 22.6 ± 8.5 g per day. There was a statistically significant difference in the mean daily DF intake between females with constipation and those without constipation (p < 0.001) but not between males (p = 0.19). These two studies found that DF intakes among females with constipation were not as relatively low as previously assumed, as they met their adequate intake of 25 g. Further data analysis from the KINGS and BREAD studies will reveal the effects of using diet to manage constipation and promote better gut health in these two cohorts of New Zealand adults.

  • Chronic constipation in people with intellectual disabilities in the community: cross-sectional study

  • Richard Laugharne, Indermeet Sawhney, Bhathika Perera, Delia Wainwright, Paul Bassett, Briony Caffrey, Maire O'Dwyer, Kirsten Lamb, Mike Wilcock, Ashok Roy, Katy Oak, Sharon Eustice, Nick Newton, James Sterritt, Ruth Bishop, Rohit Shankar
  • Journal:
    BJPsych Open / Volume 10 / Issue 2 / March 2024
    Published online by Cambridge University Press:
    01 March 2024, e55
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  • Background

    One-third to half of people with intellectual disabilities suffer from chronic constipation (defined as two or fewer bowel movements weekly or taking regular laxatives three or more times weekly), a cause of significant morbidity and premature mortality. Research on risk factors associated with constipation is limited.

    Aims

    To enumerate risk factors associated with constipation in this population.

    Method

    A questionnaire was developed on possible risk factors for constipation. The questionnaire was sent to carers of people with intellectual disabilities on the case-loads of four specialist intellectual disability services in England. Data analysis focused on descriptively summarising responses and comparing those reported with and without constipation.

    Results

    Of the 181 people with intellectual disabilities whose carers returned the questionnaire, 42% reported chronic constipation. Constipation was significantly associated with more severe intellectual disability, dysphagia, cerebral palsy, poor mobility, polypharmacy including antipsychotics and antiseizure medication, and the need for greater toileting support. There were no associations with age or gender.

    Conclusions

    People with intellectual disabilities may be more vulnerable to chronic constipation if they are more severely intellectually disabled. The associations of constipation with dysphagia, cerebral palsy, poor mobility and the need for greater toileting support suggests people with intellectual disabilities with significant physical disabilities are more at risk. People with the above disabilities need closer monitoring of their bowel health. Reducing medication to the minimum necessary may reduce the risk of constipation and is a modifiable risk factor that it is important to monitor. By screening patients using the constipation questionnaire, individualised bowel care plans could be implemented.

  • Chapter 8 - Session 3: The Explosions

  • from Part II - A Session-by-Session Guide to Feeling and Body Investigators
  • Nancy L. Zucker, Duke University Medical Center, Durham, Katharine L. Loeb, Chicago Center for Evidence Based Treatment, Martha E. Gagliano, Duke University Medical Center, Durham
  • Book:
    Treating Functional Abdominal Pain in Children
    Published online:
    18 November 2023
    Print publication:
    30 November 2023, pp 66-77

  • Summary

    Clinicians begin the Explosions! with familiar routines: a Henry Heartbeat activity, reviewing homework and adding data to the Body Map, and a new ritual: checking in with our energy and seeing if we need a snack. New characters related to processes of eating and digesting food are introduced: Victor Vomit, Gaggy Greg, Gordon Gotta Go. Investigations explore activities that may induce gagging. Equipped with garbage cans and paper towels, families are prepared for any result of these disgusting but fun investigations. Body Brainstorms explore questions such as who passes the most gas in the family and what foods produce the smelliest farts. Clinicians introduce a decision-tree in the Body Clues Worksheet that helps family members notice their body sensations, figure out what those sensations may mean (e.g., is Betty the Butterfly telling me I am excited?), and design a corresponding investigation (e.g., what happens to Betty the Butterfly if I take some deep breaths while facing my fears?). Families practice using their Body Clues Worksheet to review the highs and lows of the day or to explore the meaning of an intense moment. Armed with these new investigative tools, families are prepared for any intense situation even if it’s disgusting!

  • Chapter 11 - Session 6: The Ouchies

  • from Part II - A Session-by-Session Guide to Feeling and Body Investigators
  • Nancy L. Zucker, Duke University Medical Center, Durham, Katharine L. Loeb, Chicago Center for Evidence Based Treatment, Martha E. Gagliano, Duke University Medical Center, Durham
  • Book:
    Treating Functional Abdominal Pain in Children
    Published online:
    18 November 2023
    Print publication:
    30 November 2023, pp 97-105

  • Summary

    The Ouchies is our session about pain: emotional pain, poop pain, muscle pain, worry pain – among others. Investigations focus on the important messages of pain and explore what happens to certain pain sensations when you listen and respond to them. For example, what happens to emotional pain when you get a hug? Sample characters include Ella the Emotional Pain and Patricia the Poop Pain. Children challenge themselves to show how strong they are and how much they can do even when they feel a bit uncomfortable.

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