Skip to main content
Log in

Antipsychotic-Induced Constipation: A Review of the Pathogenesis, Clinical Diagnosis, and Treatment

  • Review Article
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Antipsychotic-induced gastrointestinal hypomotility and, in particular, its manifestation of constipation are common adverse effects in patients with schizophrenia in clinical practice. Serious complications of antipsychotic-induced constipation include ileus, ischaemic bowel disease, colon perforation, aspiration pneumonia, and bacterial septicaemia, which can be life threatening if left untreated, especially in patients prescribed clozapine. The aim of this paper is to review the latest research on the epidemiology, clinical examination methods, pathophysiology, and treatment options and preventive measures for antipsychotic-induced constipation. While clinicians are normally aware of the overall side effects caused by antipsychotics, constipation is often an under-recognized condition despite its relatively high incidence and its impact on daily living. The incidence of constipation differs among individual antipsychotics, but more than 50% of patients prescribed antipsychotics suffer from constipation. Limited fluid intake, poor dietary habits, and a sedentary lifestyle can also worsen constipation. The mechanisms of antipsychotic-induced constipation may be antagonism of cholinergic, histaminergic, and serotonergic receptors, with both parent drug and metabolite(s) contributing to the effects on gastrointestinal motility. Numerous methods, mainly divided into scale evaluations and objective examinations, are applied to evaluate antipsychotic-induced constipation; however, objective examinations have a greater ability to identify cases of gastrointestinal hypomotility since there is often an under-reporting of symptoms in subjective reporting and scale evaluation due to a higher pain threshold, an inability to express pain sensations, and a lack of symptom awareness in these patients. Antipsychotic drug-induced constipation should be closely monitored in patients receiving these medications, with timely intervention to avoid serious gastrointestinal consequences. There is currently no consensus on the efficacy of laxatives in these patients. Further in-depth studies should explore the underlying mechanisms and devise optimal therapeutic approaches to minimize constipation during antipsychotic treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Stroup TS, Gray N. Management of common adverse effects of antipsychotic medications. World Psychiatry Off J World Psychiatr Assoc (WPA). 2018;17(3):341–56. https://doi.org/10.1002/wps.20567.

    Article  Google Scholar 

  2. Sperber AD, Bangdiwala SI, Drossman DA, Ghoshal UC, Simren M, Tack J, et al. Worldwide prevalence and burden of functional gastrointestinal disorders, results of rome foundation global study. Gastroenterology. 2020. https://doi.org/10.1053/j.gastro.2020.04.014.

    Article  PubMed  Google Scholar 

  3. Chen HK, Hsieh CJ. Risk of gastrointestinal Hypomotility in schizophrenia and schizoaffective disorder treated with antipsychotics: a retrospective cohort study. Schizophr Res. 2018;195:237–44. https://doi.org/10.1016/j.schres.2017.10.024.

    Article  PubMed  Google Scholar 

  4. Nielsen J, Meyer JM. Risk factors for ileus in patients with schizophrenia. Schizophr Bull. 2012;38(3):592–8. https://doi.org/10.1093/schbul/sbq137.

    Article  PubMed  Google Scholar 

  5. Thomas N, Jain N, Connally F, Yeung JM, Pantelis C. Prucalopride in clozapine-induced constipation. Aust N Z J Psychiatry. 2018;52(8):804. https://doi.org/10.1177/0004867418774413.

    Article  PubMed  Google Scholar 

  6. Palmer SE, McLean RM, Ellis PM, Harrison-Woolrych M. Life-threatening clozapine-induced gastrointestinal hypomotility: an analysis of 102 cases. J Clin Psychiatry. 2008;69(5):759–68. https://doi.org/10.4088/jcp.v69n0509.

    Article  CAS  PubMed  Google Scholar 

  7. Cohen D, Bogers JP, van Dijk D, Bakker B, Schulte PF. Beyond white blood cell monitoring: screening in the initial phase of clozapine therapy. J Clin Psychiatry. 2012;73(10):1307–12. https://doi.org/10.4088/JCP.11r06977.

    Article  CAS  PubMed  Google Scholar 

  8. Mijovic A, MacCabe JH. Clozapine-induced agranulocytosis. Ann Hematol. 2020;99(11):2477–82. https://doi.org/10.1007/s00277-020-04215-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. De Hert M, De Beugher A, Sweers K, Wampers M, Correll CU, Cohen D. Knowledge of psychiatric nurses about the potentially lethal side-effects of clozapine. Arch Psychiatr Nurs. 2016;30(1):79–83. https://doi.org/10.1016/j.apnu.2015.09.003.

    Article  PubMed  Google Scholar 

  10. Lu Y-S, Chen Y-C, Kuo S-H, Tsai C-H. Prevalence of antipsychotic drugs related to constipation in patients with schizophrenia. Taiwanese J Psychiatry. 2016;30(4):294–9

  11. Ingimarsson O, MacCabe JH, Sigurdsson E. Constipation, ileus and medication use during clozapine treatment in patients with schizophrenia in Iceland. Nord J Psychiatry. 2018;72(7):497–500. https://doi.org/10.1080/08039488.2018.1517189.

    Article  PubMed  Google Scholar 

  12. De Hert M, Dockx L, Bernagie C, Peuskens B, Sweers K, Leucht S, et al. Prevalence and severity of antipsychotic related constipation in patients with schizophrenia: a retrospective descriptive study. BMC Gastroenterol. 2011;11:17. https://doi.org/10.1186/1471-230X-11-17.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Koizumi T, Uchida H, Suzuki T, Sakurai H, Tsunoda K, Nishimoto M, et al. Oversight of constipation in inpatients with schizophrenia: a cross-sectional study. Gen Hosp Psychiatry. 2013;35(6):649–52. https://doi.org/10.1016/j.genhosppsych.2013.06.007.

    Article  PubMed  Google Scholar 

  14. Ozbilen M, Adams CE. Systematic overview of Cochrane reviews for anticholinergic effects of antipsychotic drugs. J Clin Psychopharmacol. 2009;29(2):141–6. https://doi.org/10.1097/JCP.0b013e31819a91f1.

    Article  CAS  PubMed  Google Scholar 

  15. Ozbilen M, Adams C, Marley J. Anticholinergic effects of oral antipsychotic drugs of typicals versus atypicals over medium-and long-term: systematic review and meta-analysis. Curr Med Chem. 2012;19(30):5214–8.

    Article  CAS  Google Scholar 

  16. De Hert M, Hudyana H, Dockx L, Bernagie C, Sweers K, Tack J, et al. Second-generation antipsychotics and constipation: a review of the literature. Eur Psychiatry J Assoc Eur Psychiatr. 2011;26(1):34–44. https://doi.org/10.1016/j.eurpsy.2010.03.003.

    Article  Google Scholar 

  17. Citrome L. Cariprazine in schizophrenia: clinical efficacy, tolerability, and place in therapy. Adv Ther. 2013;30(2):114–26. https://doi.org/10.1007/s12325-013-0006-7.

    Article  CAS  PubMed  Google Scholar 

  18. Tardy M, Huhn M, Kissling W, Engel RR, Leucht S. Haloperidol versus low-potency first-generation antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2014. https://doi.org/10.1002/14651858.CD009268.pub2.

    Article  PubMed  Google Scholar 

  19. Gomez-Revuelta M, Pelayo-Teran JM, Juncal-Ruiz M, Vazquez-Bourgon J, Suarez-Pinilla P, Romero-Jimenez R, et al. Antipsychotic treatment effectiveness in first episode of psychosis: PAFIP 3-year follow-up randomized clinical trials comparing haloperidol, olanzapine, risperidone, aripiprazole, quetiapine, and ziprasidone. Int J Neuropsychopharmacol. 2020;23(4):217–29. https://doi.org/10.1093/ijnp/pyaa004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li H, Shen Y, Wang G, Shi J, Ma C, Xie S, et al. A 6-week, multicenter, double-blind, double-dummy, chlorpromazine-controlled non-inferiorityrandomized phase iiitrial to evaluate the efficacy and safety of quetiapine fumarate (SEROQUEL) extended-release (XR) in the treatment of patients with schizophrenia and acute episodes. Psychiatry Res. 2018;259:117–24. https://doi.org/10.1016/j.psychres.2017.07.006.

    Article  CAS  PubMed  Google Scholar 

  21. Sampford JR, Sampson S, Li BG, Zhao S, Xia J, Furtado VA. Fluphenazine (oral) versus atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2016;7:832. https://doi.org/10.1002/14651858.CD010832.pub2.

    Article  Google Scholar 

  22. Gomez-Revuelta M, Pelayo-Teran JM, Juncal-Ruiz M, Ortiz-Garciaoz V, Vazquez-Bourgon J, Gonzalez-Pinto A, et al. Long-term antipsychotic effectiveness in first episode of psychosis: a 3-year follow-up randomized clinical trial comparing aripiprazole, quetiapine, and ziprasidone. Int J Neuropsychopharmacol. 2018;21(12):1090–101. https://doi.org/10.1093/ijnp/pyy082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Crespo-Facorro B, de la Foz VO, Mata I, Ayesa-Arriola R, Suarez-Pinilla P, Valdizan EM, et al. Treatment of first-episode non-affective psychosis: a randomized comparison of aripiprazole, quetiapine and ziprasidone over 1 year. Psychopharmacology. 2014;231(2):357–66. https://doi.org/10.1007/s00213-013-3241-3.

    Article  CAS  PubMed  Google Scholar 

  24. Katzman MA, Brawman-Mintzer O, Reyes EB, Olausson B, Liu S, Eriksson H. Extended release quetiapine fumarate (quetiapine XR) monotherapy as maintenance treatment for generalized anxiety disorder: a long-term, randomized, placebo-controlled trial. Int Clin Psychopharmacol. 2011;26(1):11–24. https://doi.org/10.1097/YIC.0b013e32833e34d9.

    Article  PubMed  Google Scholar 

  25. Chougule A, Praharaj SK, Bhat SM, Sharma P. Prevalence and factors associated with clozapine-related constipation: an observational study. J Clin Psychopharmacol. 2018;38(1):42–6. https://doi.org/10.1097/jcp.0000000000000824.

    Article  CAS  PubMed  Google Scholar 

  26. Baptista T, Carrizo E, Fernandez E, Connell L, Servigna M, Parra A, et al. Colonic transit diagnostic test shows significant gastrointestinal hypomotility in clozapine-treated patients in comparison with subjects treated with other antipsychotics. Schizophr Res. 2015;166(1):207–11. https://doi.org/10.1016/j.schres.2015.05.025.

    Article  PubMed  Google Scholar 

  27. Every-Palmer S, Nowitz M, Stanley J, Grant E, Huthwaite M, Dunn H, et al. Clozapine-treated patients have marked gastrointestinal hypomotility, the probable basis of life-threatening gastrointestinal complications: a cross sectional study. EBioMedicine. 2016;5:125–34.

    Article  Google Scholar 

  28. Iqbal E, Govind R, Romero A, Dzahini O, Broadbent M, Stewart R, et al. The side effect profile of Clozapine in real world data of three large mental health hospitals. PLoS ONE. 2020;15(12):e0243437. https://doi.org/10.1371/journal.pone.0243437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Koller D, Almenara S, Mejía G, Saiz-Rodríguez M, Zubiaur P, Román M, et al. Safety and cardiovascular effects of multiple-dose administration of aripiprazole and olanzapine in a randomised clinical trial. Hum Psychopharmacol Clin Exp. 2021;36(1):1–12.

    Article  CAS  Google Scholar 

  30. Fava M, Mischoulon D, Iosifescu D, Witte J, Pencina M, Flynn M, et al. A double-blind, placebo-controlled study of aripiprazole adjunctive to antidepressant therapy among depressed outpatients with inadequate response to prior antidepressant therapy (ADAPT-A Study). Psychother Psychosom. 2012;81(2):87–97. https://doi.org/10.1159/000332050.

    Article  PubMed  Google Scholar 

  31. Zhang H, Li H, Shu L, Gu N, Wang G, Weng Y, et al. Double-blind comparison of ziprasidone and risperidone in the treatment of Chinese patients with acute exacerbation of schizophrenia. Neuropsychiatr Dis Treat. 2011;7:77–85. https://doi.org/10.2147/NDT.S16664.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hu S, Yao M, Peterson BS, Xu D, Hu J, Tang J, et al. A randomized, 12-week study of the effects of extended-release paliperidone (paliperidone ER) and olanzapine on metabolic profile, weight, insulin resistance, and β-cell function in schizophrenic patients. Psychopharmacology. 2013;230(1):3–13. https://doi.org/10.1007/s00213-013-3073-1.

    Article  CAS  PubMed  Google Scholar 

  33. Fu DJ, Turkoz I, Bossie CA, Patel H, Alphs L. Rapid onset of treatment effects on psychosis, depression, and mania in patients with acute exacerbation of schizoaffective disorder following treatment with oral extended-release paliperidone. J Affect Disord. 2016;193:381–90. https://doi.org/10.1016/j.jad.2015.12.060.

    Article  CAS  PubMed  Google Scholar 

  34. McEvoy JP, Byerly M, Hamer RM, Dominik R, Swartz MS, Rosenheck RA, et al. Effectiveness of paliperidone palmitate vs haloperidol decanoate for maintenance treatment of schizophrenia: a randomized clinical trial. JAMA. 2014;311(19):1978–87. https://doi.org/10.1001/jama.2014.4310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Alphs L, Bossie CA, Sliwa JK, Ma YW, Turner N. Onset of efficacy with acute long-acting injectable paliperidone palmitate treatment in markedly to severely ill patients with schizophrenia: post hoc analysis of a randomized, double-blind clinical trial. Ann Gen Psychiatry. 2011;10(1):12. https://doi.org/10.1186/1744-859x-10-12.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Raedler TJ, Reimer J, Wiedemann K. Dose-dependent constipation with higher doses of quetiapine: a case series. Int Clin Psychopharmacol. 2007;22(4):244–6. https://doi.org/10.1097/YIC.0b013e32805b71a3.

    Article  PubMed  Google Scholar 

  37. Jessurun JG, van Harten PN, Egberts TC, Pijl YJ, Wilting I, Tenback DE. The relation between psychiatric diagnoses and constipation in hospitalized patients: a cross-sectional study. Psychiatry J. 2016;2016:2459693. https://doi.org/10.1155/2016/2459693.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Shirazi A, Stubbs B, Gomez L, Moore S, Gaughran F, Flanagan RJ, et al. Prevalence and predictors of clozapine-associated constipation: a systematic review and meta-analysis. Int J Mol Sci. 2016. https://doi.org/10.3390/ijms17060863.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Every-Palmer S, Ellis PM. Clozapine-induced gastrointestinal hypomotility: a 22-year bi-national pharmacovigilance study of serious or fatal “slow gut” reactions, and comparison with international drug safety advice. CNS Drugs. 2017;31(8):699–709. https://doi.org/10.1007/s40263-017-0448-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Every-Palmer S, Inns SJ, Ellis PM. Constipation screening in people taking clozapine: a diagnostic accuracy study. Schizophr Res. 2020;220:179–86. https://doi.org/10.1016/j.schres.2020.03.032.

    Article  PubMed  Google Scholar 

  41. Schneider C, Corrigall R, Hayes D, Kyriakopoulos M, Frangou S. Systematic review of the efficacy and tolerability of clozapine in the treatment of youth with early onset schizophrenia. Eur Psychiatry J Assoc Eur Psychiatr. 2014;29(1):1–10. https://doi.org/10.1016/j.eurpsy.2013.08.001.

    Article  CAS  Google Scholar 

  42. Bobes J, Arango C, Aranda P, Carmena R, Garcia-Garcia M, Rejas J, et al. Cardiovascular and metabolic risk in outpatients with schizophrenia treated with antipsychotics: results of the CLAMORS Study. Schizophr Res. 2007;90(1–3):162–73. https://doi.org/10.1016/j.schres.2006.09.025.

    Article  PubMed  Google Scholar 

  43. Singh MK, Giles LL, Nasrallah HA. Pain insensitivity in schizophrenia: trait or state marker? J Psychiatr Pract. 2006;12(2):90–102. https://doi.org/10.1097/00131746-200603000-00004.

    Article  PubMed  Google Scholar 

  44. Jakobsen AS, Speyer H, Norgaard HCB, Karlsen M, Hjorthoj C, Krogh J, et al. Dietary patterns and physical activity in people with schizophrenia and increased waist circumference. Schizophr Res. 2018;199:109–15. https://doi.org/10.1016/j.schres.2018.03.016.

    Article  PubMed  Google Scholar 

  45. Bharucha AE, Lacy BE. Mechanisms, evaluation, and management of chronic constipation. Gastroenterology. 2020. https://doi.org/10.1053/j.gastro.2019.12.034.

    Article  PubMed  Google Scholar 

  46. Bharucha AE, Wald A. Chronic constipation. Mayo Clin Proc. 2019;94(11):2340–57. https://doi.org/10.1016/j.mayocp.2019.01.031.

    Article  PubMed  Google Scholar 

  47. World Health Organization. Role of anticholinergic medications in patients requiring long-term antipsychotic treatment for psychotic disorders. 2012. https://www.who.int/mental_health/mhgap/evidence/psychosis/q6/en/. Accessed 27 May 2021.

  48. Sarangi A, Armin S, Vargas A, Chu VM, Fain K, Nelson J. Management of constipation in patients with schizophrenia—a case study and review of literature. Middle East Curr Psychiatry. 2021;28(1):1–7.

    Article  Google Scholar 

  49. Silverman M, Aroniadis OC, Feuerstadt P, Fenster M, Huisman T, Mansoor MS, et al. Older patients are significantly more likely to have colon ischaemia-associated conditions that are chronic and complex. Aliment Pharmacol Ther. 2019;49(12):1502–8. https://doi.org/10.1111/apt.15268.

    Article  PubMed  Google Scholar 

  50. Feinberg M. The problems of anticholinergic adverse effects in older patients. Drugs Aging. 1993;3(4):335–48. https://doi.org/10.2165/00002512-199303040-00004.

    Article  CAS  PubMed  Google Scholar 

  51. Bharucha AE, Pemberton JH, Locke GR. American gastroenterological association technical review on constipation. Gastroenterology. 2013;144(1):218–38. https://doi.org/10.1053/j.gastro.2012.10.028.

    Article  PubMed  Google Scholar 

  52. Every-Palmer S, Lentle RG, Reynolds G, Hulls C, Chambers P, Dunn H, et al. Spatiotemporal mapping techniques show clozapine impairs neurogenic and myogenic patterns of activity in the colon of the rabbit in a dose-dependent manner. Front Pharmacol. 2017;8:209. https://doi.org/10.3389/fphar.2017.00209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Huhn M, Nikolakopoulou A, Schneider-Thoma J, Krause M, Samara M, Peter N, et al. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet. 2019;394(10202):939–51.

    Article  CAS  Google Scholar 

  54. Solismaa A, Kampman O, Lyytikainen LP, Seppala N, Viikki M, Mononen N, et al. Genetic polymorphisms associated with constipation and anticholinergic symptoms in patients receiving clozapine. J Clin Psychopharmacol. 2018;38(3):193–9. https://doi.org/10.1097/JCP.0000000000000885.

    Article  CAS  PubMed  Google Scholar 

  55. Schuster P, Gabriel E, Kufferle B, Strobl G, Karobath M. Reversal by physostigmine of clozapine-induced delirium. Clin Toxicol. 1977;10(4):437–41. https://doi.org/10.3109/15563657709046281.

    Article  CAS  PubMed  Google Scholar 

  56. Every-Palmer S, Inns SJ, Grant E, Ellis PM. Effects of clozapine on the gut: cross-sectional study of delayed gastric emptying and small and large intestinal dysmotility. CNS Drugs. 2019;33(1):81–91. https://doi.org/10.1007/s40263-018-0587-4.

    Article  CAS  PubMed  Google Scholar 

  57. Hermann B, Wetzel CH, Pestel E, Zieglgansberger W, Holsboer F, Rupprecht R. Functional antagonistic properties of clozapine at the 5-HT3 receptor. Biochem Biophys Res Commun. 1996;225(3):957–60. https://doi.org/10.1006/bbrc.1996.1278.

    Article  CAS  PubMed  Google Scholar 

  58. Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, et al. H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2003;28(3):519–26. https://doi.org/10.1038/sj.npp.1300027.

    Article  CAS  Google Scholar 

  59. Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007;132(1):397–414. https://doi.org/10.1053/j.gastro.2006.11.002.

    Article  CAS  PubMed  Google Scholar 

  60. Gershon MD. Review article: serotonin receptors and transporters—roles in normal and abnormal gastrointestinal motility. Aliment Pharmacol Ther. 2004;20(Suppl 7):3–14. https://doi.org/10.1111/j.1365-2036.2004.02180.x.

    Article  CAS  PubMed  Google Scholar 

  61. Bailey L, Varma S, Ahmad N, Gee S, Taylor DM. Factors predicting use of laxatives in outpatients stabilized on clozapine. Ther Adv Psychopharmacol. 2015;5(5):256–62. https://doi.org/10.1177/2045125315591917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. DiCello JJ, Saito A, Rajasekhar P, Sebastian BW, McQuade RM, Gondin AB, et al. Agonist-dependent development of delta opioid receptor tolerance in the colon. Cell Mol Life Sci CMLS. 2019;76(15):3033–50. https://doi.org/10.1007/s00018-019-03077-6.

    Article  CAS  PubMed  Google Scholar 

  63. Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006;130(5):1377–90. https://doi.org/10.1053/j.gastro.2006.03.008.

    Article  PubMed  Google Scholar 

  64. Drossman DA, Hasler WL. Rome IV-functional GI disorders: disorders of gut–brain interaction. Gastroenterology. 2016;150(6):1257–61. https://doi.org/10.1053/j.gastro.2016.03.035.

    Article  PubMed  Google Scholar 

  65. McMillan SC, Williams FA. Validity and reliability of the constipation assessment scale. Cancer Nurs. 1989;12(3):183–8. https://doi.org/10.1097/00002820-198906000-00012.

    Article  CAS  PubMed  Google Scholar 

  66. Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997;32(9):920–4. https://doi.org/10.3109/00365529709011203.

    Article  CAS  PubMed  Google Scholar 

  67. Blake MR, Raker JM, Whelan K. Validity and reliability of the Bristol Stool Form Scale in healthy adults and patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2016;44(7):693–703. https://doi.org/10.1111/apt.13746.

    Article  CAS  PubMed  Google Scholar 

  68. Kim ER, Rhee P-L. How to interpret a functional or motility test—colon transit study. J Neurogastroenterol Motil. 2012;18(1):94–9. https://doi.org/10.5056/jnm.2012.18.1.94.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Parthasarathy G, Chen J, Chen X, Chia N, O’Connor HM, Wolf PG, et al. Relationship between microbiota of the colonic mucosa vs feces and symptoms, colonic transit, and methane production in female patients with chronic constipation. Gastroenterology. 2016;150(2):367-79.e1. https://doi.org/10.1053/j.gastro.2015.10.005.

    Article  PubMed  Google Scholar 

  70. Every-Palmer S, Ellis PM, Nowitz M, Stanley J, Grant E, Huthwaite M, et al. The porirua protocol in the treatment of clozapine-induced gastrointestinal hypomotility and constipation: a pre- and post-treatment study. CNS Drugs. 2017;31(1):75–85. https://doi.org/10.1007/s40263-016-0391-y.

    Article  CAS  PubMed  Google Scholar 

  71. Grønlund D, Vase L, Knudsen SA, Christensen M, Drewes AM, Olesen AE. Comparison of subjective and objective measures of constipation—employing a new method for categorizing gastrointestinal symptoms. J Pharmacol Toxicol Methods. 2018;94(Pt 2):23–8. https://doi.org/10.1016/j.vascn.2018.08.002.

    Article  CAS  PubMed  Google Scholar 

  72. De Hert M, Correll CU, Bobes J, Cetkovich-Bakmas M, Cohen D, Asai I, et al. Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care. World Psychiatry Off J World Psychiatr Assoc (WPA). 2011;10(1):52.

    Google Scholar 

  73. Dworkin RH. Pain insensitivity in schizophrenia: a neglected phenomenon and some implications. Schizophr Bull. 1994;20(2):235–48. https://doi.org/10.1093/schbul/20.2.235.

    Article  CAS  PubMed  Google Scholar 

  74. Ohashi K, Himaki D, Nagao K, Kawai M, Gale JD, Furness JB, et al. A selective, high affinity 5-HT 2B receptor antagonist inhibits visceral hypersensitivity in rats. Neurogastroenterol Motil Off J Eur Gastrointestinal Motil Soc. 2010;22(2):69–76. https://doi.org/10.1111/j.1365-2982.2009.01395.x.

    Article  CAS  Google Scholar 

  75. De Ponti F. Pharmacology of serotonin: what a clinician should know. Gut. 2004;53(10):1520–35. https://doi.org/10.1136/gut.2003.035568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Lee YJ, Park KS. Understanding the changes in diagnostic criteria for functional constipation in pediatric patients: from rome III to rome IV. J Neurogastroenterol Motil. 2019;25(1):3–5. https://doi.org/10.5056/jnm18199.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Bishara D, Taylor D. Adverse effects of clozapine in older patients: epidemiology, prevention and management. Drugs Aging. 2014;31(1):11–20. https://doi.org/10.1007/s40266-013-0144-2.

    Article  CAS  PubMed  Google Scholar 

  78. Bak M. Monitoring clozapine adverse effects calls for the integration of protocol and good clinical practice. J Clin Psychiatry. 2012;73(10):1313–4. https://doi.org/10.4088/JCP.12com07964.

    Article  CAS  PubMed  Google Scholar 

  79. Hayat U, Dugum M, Garg S. Chronic constipation: update on management. Cleve Clin J Med. 2017;84(5):397–408. https://doi.org/10.3949/ccjm.84a.15141.

    Article  PubMed  Google Scholar 

  80. Camilleri M, Ford AC, Mawe GM, Dinning PG, Rao SS, Chey WD, et al. Chronic constipation. Nat Rev Dis Primers. 2017;3:17095. https://doi.org/10.1038/nrdp.2017.95.

    Article  PubMed  Google Scholar 

  81. Suzuki T, Uchida H, Watanabe K, Kashima H. Minimizing antipsychotic medication obviated the need for enema against severe constipation leading to paralytic ileus: a case report. J Clin Pharm Ther. 2007;32(5):525–7. https://doi.org/10.1111/j.1365-2710.2007.00843.x.

    Article  CAS  PubMed  Google Scholar 

  82. Kwiatkowski M, Denka ZD, White CC. Paralytic ileus requiring hospitalization secondary to high-dose antipsychotic polypharmacy and benztropine. Gen Hosp Psychiatry. 2011;33(2):200.e5-7. https://doi.org/10.1016/j.genhosppsych.2010.10.005.

    Article  Google Scholar 

  83. Rege S, Lafferty T. Life-threatening constipation associated with clozapine. Aust Psychiatry Bull R Aust N Zeal Coll Psychiatr. 2008;16(3):216–9. https://doi.org/10.1080/10398560701882203.

    Article  Google Scholar 

  84. Meyer JM, Cummings MA. Lubiprostone for treatment-resistant constipation associated with clozapine use. Acta Psychiatr Scand. 2014;130(1):71–2. https://doi.org/10.1111/acps.12259.

    Article  CAS  PubMed  Google Scholar 

  85. Poetter CE, Stewart JT. Treatment of clozapine-induced constipation with bethanechol. J Clin Psychopharmacol. 2013;33(5):713–4. https://doi.org/10.1097/JCP.0b013e3182a1160d.

    Article  PubMed  Google Scholar 

  86. Damodaran I, Hui KO, Nordin ASA, Yee A, Gill JS, Francis B, et al. An open-label, head to head comparison study between prucalopride and lactulose for clozapine induced constipation in patients with treatment resistant schizophrenia. Healthc (Basel Switz). 2020. https://doi.org/10.3390/healthcare8040533.

    Article  Google Scholar 

  87. Lacy BE, Levy LC. Lubiprostone: a novel treatment for chronic constipation. Clin Interv Aging. 2008;3(2):357–64. https://doi.org/10.2147/cia.s2938.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Nakamura M, Nagamine T. Prevalence and predictors of laxatives use in clozapine-related constipation: an observational study. Int Clin Psychopharmacol. 2021;36(3):162–7. https://doi.org/10.1097/yic.0000000000000354.

    Article  PubMed  Google Scholar 

  89. Every-Palmer S, Newton-Howes G, Clarke MJ. Pharmacological treatment for antipsychotic-related constipation. Schizophr Bull. 2017. https://doi.org/10.1093/schbul/sbx011.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Rao SS, Rattanakovit K, Patcharatrakul T. Diagnosis and management of chronic constipation in adults. Nat Rev Gastroenterol Hepatol. 2016;13(5):295–305. https://doi.org/10.1038/nrgastro.2016.53.

    Article  CAS  PubMed  Google Scholar 

  91. George J, Hotham R, Melton W, Chapple K. Clozapine-induced stercoral colitis: a surgical perspective. BMJ Case Rep. 2019. https://doi.org/10.1136/bcr-2018-227718.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiangrong Zhang.

Ethics declarations

Funding

This work was supported by the National Key Research and Development Program of China (2018YFC1314300), the National Natural Science Foundation of China (81971255), the Social Development Foundation of Jiangsu Province, China (No. BE2019610), and the Jiangsu Provincial Medical Talent project of China (ZDRCA2016075).

Conflict of interest

The authors declared no conflicts of interest that are relevant to the contents of this review.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Author contributions

YX drafted and revised the manuscript. NA polished the language and revised the manuscript. YX and NA contributed equally to the work. XRZ designed the framework of manuscript and guided the writing and revision of the manuscript. YX, NA, and XRZ approved the final version and agreed to be accountable for its contents.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, Y., Amdanee, N. & Zhang, X. Antipsychotic-Induced Constipation: A Review of the Pathogenesis, Clinical Diagnosis, and Treatment. CNS Drugs 35, 1265–1274 (2021). https://doi.org/10.1007/s40263-021-00859-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40263-021-00859-0

Navigation