Published: 1 June 2023

Publications

Antipsychotic-induced constipation – high impact for patients

Published: 1 June 2023
Prescriber Update 44(2): 24–26
June 2023

Antipsychotics are a class of medicines that are indicated for the treatment of schizophrenia and related disorders.¹

Constipation is a common side effect of all antipsychotics that can occur at any stage of treatment.¹

Regular monitoring of bowel movements is essential throughout antipsychotic treatment. Constipation is a risk factor for serious bowel-related complications if not detected and managed appropriately.^2,3

Antipsychotics impact bowel motility

The neurotransmitters acetylcholine, serotonin and histamine play a role in promoting intestinal peristalsis, a mechanism required to push intestinal content through the colon to the rectum.³

Antipsychotics can inhibit the action of one or more of these neurotransmitters, resulting in prolonged gastrointestinal transit time, which contributes to constipation.³

The risk of constipation differs between antipsychotics, due to varying affinity with different neurotransmitter receptor types.^2,3

Serious bowel-related adverse events with some antipsychotics

Untreated or delayed diagnosis of antipsychotic-induced constipation may increase the risk of ileus and/or intestinal obstruction.^2,3

Complications of an intestinal obstruction can include intestinal ischaemia, intestinal necrosis and intestinal perforation. If these complications occur, patients require hospital admission and may need surgery.⁵

Serious bowel-related adverse events can occur at any time during treatment with antipsychotics, although the risk is higher with clozapine.^2,4 On rare occasions these events have proved fatal.⁴

Risk factors for developing antipsychotic-induced constipation

Some patients may have risk factors for developing constipation with antipsychotics, including concomitant medicine use, lifestyle factors, co-morbidities and antipsychotic dose.

Constipation is an adverse reaction of many medicines, including opioids or medicines with anticholinergic properties.³ Be cautious about concomitant prescribing, especially for patients already taking clozapine.^3,4

Lifestyle and dietary factors can contribute to constipation in people with schizophrenia. This includes poor dietary habits, limited fluid intake and low physical activity.^2,3

Patients who are elderly, have a history of colonic disease or a history of lower abdominal surgery may be at a higher risk of constipation.^3,4

The risk of antipsychotic-induced constipation may be dose related.³

Early detection and management are vital

The most commonly reported signs and symptoms associated with severe constipation include moderate to severe abdominal pain, abdominal distension, vomiting, paradoxical ‘overflow’ diarrhoea, reduced appetite and nausea. However, many patients with schizophrenia have abnormally high pain tolerance, and may not report symptoms associated with constipation.⁶

Members of the treating team should regularly ask patients about their bowel movements. Remind patients to monitor their bowel movements frequently. Whānau and caregivers could also be asked to help monitor the patient.^3,4

Prescribers should advise patients to seek immediate medical attention when constipation occurs.^3,4

Close monitoring of the patient’s bowel movements is essential throughout treatment with clozapine. It is vital that constipation is recognised early and treated appropriately. As described above, complications can occur with delayed diagnosis.⁴

Management of antipsychotic-induced constipation may include non-pharmacological and/or pharmacological treatments.³ With clozapine, prophylactic use of laxatives may be required. Follow local clinical guidelines.⁴

New Zealand case reports

The Centre for Adverse Reaction reporting (CARM) has received numerous reports of bowel-related adverse events with antipsychotics. Most of them are associated with clozapine (Table 1).

Table 1: Clozapine and significant gastrointestinal events reported to the Centre for Adverse Reactions Monitoring (CARM), by reported reaction term, as of 22 March 2023

Reaction term	Number of reports*
Constipation	95
Intestinal obstruction	32
Megacolon acquired	10
Ileus	9
Bowel motility disorder	8
Intestinal perforation, intestinal ischaemia, ileus paralytic, faecal impaction	4 (each)
Colitis	3
Gastrointestinal haemorrhage, peritonitis	2 (each)
Colitis ischaemic, small intestine obstruction, intestinal necrosis	1 (each)

* An individual report can have multiple reaction terms and may be represented in more than one of the reaction term counts.

Source: Centre for Adverse Reactions Monitoring

As of 22 March 2023, the bowel-related adverse events reported with other antipsychotics were:

• constipation: risperidone (2 reports); amisulpride, flupentixol, chlorpromazine, quetiapine, haloperidol (1 report each)
• bowel motility disorder: olanzapine (1)
• colitis: risperidone (1).

More information

For more information about antipsychotics, see the data sheet and consumer medicines information(CMI): Search for a data sheet or CMI.

For further information about clozapine:

• Prescriber Update June 2015: Clozapine – Close Monitoring Required
• Prescriber Update June 2011: Clozapine: Impacts on the colon
• Medsafe June 2020: Clozapine – Alert Communication: Important updates to clozapine data sheets and monitoring during COVID-19 pandemic

References

1. New Zealand Formulary (NZF). 2022. NZF v130: Antipyschotic drugs 01 Apr 2023. URL: nzf.org.nz/nzf_2098 (accessed 4 April 2023).
2. De Hert M, Hudyana H, Dockx L, et al. 2011. Second-generation antipsychotics and constipation: a review of the literature. European Psychiatry 26(1): 34-44. DOI: 10.1016/j.eurpsy.2010.03.003 (accessed 4 April 2023).
3. Xu Y, Amdanee N and Zhang X. 2021. Antipsychotic-induced constipation: a review of the pathogenesis, clinical diagnosis, and treatment. CNS Drugs 35(12): 1265–74. DOI: 10.1007/s40263-021-00859-0 (accessed 4 April 2023).
4. Viatris Ltd. 2023. Clozaril New Zealand Data Sheet. 13 March 2023. URL: medsafe.govt.nz/profs/Datasheet/c/Clozariltab.pdf (accessed 4 April 2023).
5. Smith DA, Kashyap S, Nehring SM. 2022. Bowel obstruction. In: Statpearls [Internet]. URL: ncbi.nlm.nih.gov/books/NBK441975/ (accessed 5 April 2023).
6. Medsafe. 2015. Clozapine – Close monitoring required. Prescriber Update 36(2): 18-21. URL: medsafe.govt.nz/profs/puarticles/June2015/June2015Clozapine.htm (accessed 21 April 2023).