Which medicines and supplements are known to cause constipation, and how often do they do it?

What it is

Drug-induced constipation is constipation caused or worsened by something a person takes. The groups most often named are opioids, drugs with anticholinergic action (including bladder antimuscarinics and tricyclic antidepressants), calcium channel blockers, antipsychotics - clozapine above all - 5-HT3 antagonists such as ondansetron, iron salts, calcium salts, aluminium-containing antacids, antiepileptics and diuretics. Rates vary enormously between drugs and between how hard a study looked for the symptom.

What the research says

Where trials and meta-analyses report numbers, the size of the effect is measurable rather than theoretical: bladder anticholinergics roughly double the odds of constipation versus placebo, 5-HT3 antagonists raise the relative risk about 3.7-fold, clozapine-associated constipation pools at 31.2%, ferrous sulfate constipation pools at 12% of people, and in hospital data the risk of severe constipation differs clearly between opioids and rises with daily dose. Other listed causes - diuretics, antiepileptics, aluminium antacids - rest mainly on agency lists and clinical experience rather than quantified trial rates in what we could reach, and at least one cross-sectional study found calcium supplements were not an independent risk factor.

Evidence grade: Well established.

What goes wrong

Clozapine-related gut slowing can be fatal: a third of reported cases in a 25-year national pharmacovigilance series died. (Source 1)

• Case series, Low certainty.
• Size: 527 reported patients, of whom 172 died.
• Who: patients prescribed clozapine in the United Kingdom, 1992-2017.
• How long: up to 25 years of reporting; deaths rose from 1 per year 1992-1999 to 15 per year 2010-2017.
• Result: 33% (n = 172) of 527 reported patients died; 3% fatal within the first 4 years of treatment versus 25% at 10-14 years; surgery was the commonest non-fatal outcome (n = 92), including colectomy and stoma formation; clozapine was discontinued permanently in at least 76 patients.
• Funding: not stated.

There were 527 patients reported with potentially harmful CIGH; 33% (n = 172) died.

Constipation from medicines is often not fixed by simply adding a laxative. (Source 2)

• Survey study, Low certainty.
• Size: 1,134 of 8,621 patients were taking a constipation medicine.
• Who: patients undergoing colonoscopy at a single Japanese centre - a clinic population selected for bowel investigation, not a general-population sample.
• How long: single time point.
• Result: 13.2% were taking a medicine for constipation, yet refractory symptoms persisted in 61.4% of them; diabetes OR 1.5 (p = 0.028) and IBS OR 3.1 (p < 0.001) predicted refractory symptoms.
• Funding: not stated.

The number of patients taking any medication for constipation was 1,134 (13.2%); however, refractory symptoms of constipation were still present in 61.4% of these patients.

What the evidence supports

Bladder anticholinergics roughly double the odds of constipation compared with placebo, with the effect present for every individual drug studied. (Source 3)

• Meta-analysis, Moderate certainty.
• Size: randomised placebo-controlled trials; 6 to 10 RCTs per drug.
• Who: adults with overactive bladder.
• How long: trial durations not stated in the abstract.
• Result: overall OR 2.18 (95% CI 1.82 to 2.60, I2 29.4%); darifenacin OR 1.93 (1.40-2.66); fesoterodine 2.07 (1.28-3.35); oxybutynin 2.34 (1.31-4.16); solifenacin 3.02 (2.37-3.84); tolterodine 1.36 (1.01-1.85); trospium 2.93 (2.00-4.28)
• Funding: not stated.

The use of anticholinergic agents was associated with a significantly greater rate of constipation in adults with overactive bladder (OR 2.18, 95% CI 1.82 to 2.60; I2=29.4%) compared with placebo.

The risk of severe constipation differs between opioids and rises with daily opioid dose. (Source 4)

• Cohort study, Moderate certainty.
• Size: 80,475 patients given an opioid in hospital.
• Who: adults treated with opioids for non-cancer pain in Northwest England hospitals.
• How long: from first opioid prescription to first constipation event, discharge, or end of study.
• Result: versus codeine: morphine HR 1.59 (95% CI 1.45-1.74), oxycodone 1.46 (1.32-1.63), fentanyl 1.37 (1.14-1.64), combination opioids 1.85 (1.66-2.06), tramadol 0.80 (0.64-1.00); 50 to <120 MME/day HR 1.95 (1.78-2.15) versus <50 MME/day.
• Funding: Nuffield Foundation Oliver Bird Fund, Versus Arthritis and an NIHR Advanced Fellowship.

Compared to codeine, morphine (HR 1.59, 95% CI 1.45–1.74), oxycodone (HR 1.46, 95% CI 1.32–1.63), fentanyl (HR 1.37, 95% CI 1.14–1.64) and combination opioids (HR 1.85, 95% CI 1.66–2.06) were associated with a higher risk of constipation

In a patient survey, two thirds of people taking opioids reported opioid-induced constipation, and most of those described at least one severe symptom. (Source 5)

• Survey study, Low certainty.
• Size: 597 participants.
• Who: people taking opioids for cancer-related pain (25%) and non-cancer pain (75%)
• How long: single survey.
• Result: 66% experienced opioid-induced constipation; 58% of non-cancer pain patients with OIC and 83% of cancer pain patients reported at least one severe or very severe constipation symptom.
• Funding: supported by the Paolo Procacci Foundation.

Of the 597 participants, 150 (25%) had cancer-related pain, and 447 (75%) had non-cancer pain; 66% experienced OIC.

Clozapine-associated constipation pools at about 31% of patients, three times the odds seen with other antipsychotics. (Source 6)

• Meta-analysis, Moderate certainty.
• Size: 32 studies; n = 2,013 for the prevalence estimate; 11 studies for the comparison.
• Who: people treated with clozapine, inpatient and outpatient.
• How long: not stated.
• Result: pooled prevalence 31.2% (95% CI 25.6-37.4); versus other antipsychotics OR 3.02 (95% CI 1.91-4.77), p < 0.001; 36.9% when constipation was a specified outcome versus 24.8% when it was not (p = 0.048)
• Funding: not stated in the fetched text.

A total of 32 studies were meta-analyzed, establishing a pooled prevalence of clozapine-associated constipation of 31.2% (95% CI: 25.6–37.4) (n = 2013).

Ferrous sulfate causes constipation in about one person in eight across trials, alongside nausea and diarrhoea. (Source 7)

• Meta-analysis, Moderate certainty.
• Size: 27 studies reported constipation, within 43 studies overall.
• Who: adults taking oral ferrous sulfate in randomised trials.
• How long: trial durations not stated in the passage.
• Result: pooled incidence of constipation in the ferrous sulfate arm 12% (95% CI 10%-15%); nausea 11% (8%-14%); diarrhoea 8% (6%-11%)
• Funding: UK Medical Research Council (U105960399 and G0800860), with no role in design or analysis.

For the 27 studies that reported constipation, the pooled estimate of incidence in the FeSO4 arm was 12% [95% CI 10%-15%].

5-HT3 receptor antagonists such as ondansetron raise the relative risk of constipation almost four-fold compared with placebo. (Source 8)

• Meta-analysis, Moderate certainty.
• Size: randomised controlled trials in irritable bowel syndrome; trial count not stated in the passage.
• Who: adults with irritable bowel syndrome, including IBS-D and non-constipated IBS.
• How long: trial durations not stated.
• Result: pooled RR of constipation 3.71 (95% CI 2.98-4.61); non-constipated IBS and IBS-D RR 5.28 (3.93-7.08) versus IBS-D only 3.24 (2.54-4.12)
• Funding: National Natural Science Foundation of China (No. 81470813)

5-HT3 receptor antagonists were likelier to cause constipation: the pooled RR of constipation developing with 5-HT3 receptor antagonist versus placebo was 3.71 (95% CI: 2.98–4.61).

In a cross-sectional hospital study, opioid, antiparkinsonian and benzodiazepine use were each independently associated with constipation symptoms. (Source 2)

• Survey study, Low certainty.
• Size: 8,621 patients.
• Who: patients undergoing colonoscopy at a single Japanese centre - a clinic population selected for bowel investigation, not a general-population sample.
• How long: single time point.
• Result: opioid use OR 2.1 (p = 0.002), antiparkinsonian medications OR 1.9 (p = 0.030), benzodiazepine use OR 1.7 (p < 0.001)
• Funding: not stated.

benzodiazepine use (OR 1.7, p < 0.001), antiparkinsonian

A US government body lists the medicine and supplement groups it regards as making constipation worse, including aluminium- and calcium-containing antacids, anticonvulsants, calcium channel blockers, diuretics and iron. (Source 9)

• Official position, Certainty not rated.
• Size: not applicable - agency health information page.
• Who: general public.
• How long: current at the date of the page.
• Result: no rates given.
• Funding: United States government agency.

antacids that contain aluminum and calcium

A US government body states that calcium supplements can cause constipation and that calcium carbonate does so more than calcium citrate. (Source 10)

• Official position, Certainty not rated.
• Size: not applicable - agency fact sheet.
• Who: people taking calcium supplements, with older adults singled out.
• How long: current at the date of the page.
• Result: no rates given; calcium carbonate said to cause more gastrointestinal side effects than calcium citrate, especially in older adults with lower stomach acid.
• Funding: United States government agency.

Some individuals who take calcium supplements might experience gastrointestinal side effects, including gas, bloating, constipation, or a combination of these symptoms.

What the evidence does not support

In one community study of older people, calcium supplements and ACE inhibitors were not independent risk factors for constipation. (Source 11)

• Survey study, Very low certainty.
• Size: 236 valid surveys from 1,110 mailed.
• Who: community-dwelling older adults in Greater Western Sydney, Australia.
• How long: single survey, 21.3% return rate.
• Result: calcium supplements (ATC A12A) and ACE inhibitors (C09A) not independent risk factors at the 5% level; opioids were significantly associated.
• Funding: not stated.

Calcium supplements (A12A) and angiotensin converting enzyme (ACE) inhibitor (C09A) were not independent risk factors for constipation at 5% level of significance.

Where the evidence is mixed

Amitriptyline, a tricyclic with anticholinergic action, raised the risk of any adverse event by half in placebo-controlled trials, but the Cochrane review did not report constipation as a separate rate. (Source 12)

• Systematic review, Low certainty.
• Size: 519 participants across six placebo-controlled studies for the adverse event outcome.
• Who: adults treated with amitriptyline for neuropathic pain.
• How long: trial durations not stated in the passage.
• Result: at least one adverse event in 148/269 (55%) on amitriptyline versus 89/250 (36%) on placebo; RR 1.5 (1.3 to 1.8); NNH 5.2 (3.6 to 9.1); serious adverse events 8/122 (6.6%) versus 2/114 (1.8%)
• Funding: Cochrane review; funding not stated in the passage read.

At least one adverse event was experienced by 148/269 (55%) of participants taking amitriptyline, and 89/250 (36%) taking placebo. The RR was 1.5 (1.3 to 1.8) (Analysis 1.2), and the NNH was 5.2 (3.6 to 9.1).

Where the research disagrees

Whether calcium supplements are a genuine cause of constipation

• Office of Dietary Supplements, National Institutes of Health, fact sheet read 2026-09-23, position: Some individuals who take calcium supplements might experience gastrointestinal side effects, including gas, bloating, constipation, or a combination of these symptoms. (Source 10)
• Fragakis and colleagues, International Journal of Environmental Research and Public Health 2018, cross-sectional survey of 236 older adults: Calcium supplements (A12A) and angiotensin converting enzyme (ACE) inhibitor (C09A) were not independent risk factors for constipation at 5% level of significance. (Source 11)

A common belief, and what the research shows

The belief: Constipation from a medicine is a minor nuisance that a laxative will sort out.

What the research shows: Sometimes, but not reliably. In 8,621 hospital patients, "refractory symptoms of constipation were still present in 61.4% of these patients" who were already taking something for it. And for clozapine the pharmacovigilance record shows the slowed gut can kill: "There were 527 patients reported with potentially harmful CIGH; 33% (n = 172) died."

Questions and answers

What does it mean when a medicine is a known constipation causer?

It means trials, meta-analyses or safety reporting have linked that drug to constipation more often than a comparator, or that a health agency lists it as a cause. A US government body names aluminium- and calcium-containing antacids, anticholinergics and antispasmodics, anticonvulsants, calcium channel blockers, diuretics, iron supplements, Parkinson's medicines, narcotic pain medicines and some antidepressants. The strength of the underlying evidence differs a lot between those groups. (Source 9)

What do these drugs do in the body to slow things down?

The mechanisms the literature describes are mostly about gut nerves and muscle. Anticholinergic drugs block muscarinic signalling that drives colonic motility, and pooled trial data show every bladder antimuscarinic studied raised constipation versus placebo. 5-HT3 antagonists block serotonin signalling used in gut motility, which is why they are also used to slow diarrhoea, and the same action produces constipation. (Source 8)

Are these medicines bad for me, then?

The literature does not say that, and Memios does not give medical advice. It says constipation is a measurable side effect that differs between drugs in the same class - for example, versus codeine, tramadol carried a lower risk of severe constipation (HR 0.80, 95% CI 0.64-1.00) while combination opioids carried a higher one (HR 1.85, 1.66-2.06). For clozapine, the same gut slowing has been fatal in a minority of reported cases, which is why bowel monitoring is discussed in that literature. (Source 4)

Which of these has the highest reported rate?

Among the figures we could source, opioid-induced constipation was reported by 66% of 597 people surveyed, clozapine-associated constipation pooled at 31.2% across 32 studies, ferrous sulfate constipation pooled at 12% of trial participants, and 5-HT3 antagonists raised the relative risk 3.71-fold versus placebo. Rates rise when a study looks for constipation deliberately: 36.9% when it was a specified outcome versus 24.8% when it was not. (Source 6)

If a medicine is causing it, what does the literature say reduces the problem?

The drug-level evidence is about which drug and how much: in 80,475 hospital patients, doses of 50 to under 120 morphine milligram equivalents a day carried HR 1.95 (95% CI 1.78-2.15) for constipation compared with under 50. A government fact sheet notes that switching the form of calcium, splitting doses or taking it with meals is used to ease calcium supplement side effects. None of this is advice about your own prescription. (Source 10)

Why does one person on a drug get constipated and another does not?

The studies report modifiers rather than mechanisms for individuals. For clozapine, rates were higher in inpatients than outpatients and higher where constipation was actively measured. For opioids, dose and the specific opioid changed the risk. In a hospital population, diabetes and irritable bowel syndrome predicted which people stayed constipated despite treatment. (Source 6)

Are there supplements from food sources that do this too?

Yes - the two supplement groups with the clearest signal are iron and calcium. Ferrous sulfate constipation pooled at 12% of trial participants across 27 studies, and a US government body states calcium supplements can cause constipation, with calcium carbonate worse than calcium citrate. Against that, one community survey of older adults did not find calcium supplements an independent risk factor. (Source 10)

What happens if drug-induced constipation is ignored?

For most drugs the literature reports symptoms and quality-of-life burden rather than hard outcomes: 58% of people with non-cancer pain and opioid-induced constipation reported at least one severe or very severe symptom. For clozapine, the pharmacovigilance record is much starker - of 527 reported cases of clozapine-induced gut hypomotility, 33% died, and surgery was the commonest non-fatal outcome. (Source 1)

Can you test whether a medicine is the cause?

There is no test that names a drug as the culprit. What the literature offers is base rates to compare against - pooled prevalences, odds ratios and hazard ratios - plus the observation that constipation is found far more often when someone looks for it. Clozapine work explicitly contrasts studies where constipation was a specified outcome (36.9%) with studies where it was not (24.8%). (Source 6)

How much do opioids actually raise the risk, and does the dose matter?

In 80,475 hospital patients given opioids for non-cancer pain, risk of severe constipation differed by drug and by dose. Compared with codeine, morphine carried HR 1.59 (95% CI 1.45-1.74), oxycodone 1.46 (1.32-1.63), fentanyl 1.37 (1.14-1.64) and combination opioids 1.85 (1.66-2.06). Daily doses of 50 to under 120 morphine milligram equivalents carried HR 1.95 (1.78-2.15) versus under 50. (Source 4)

Do antidepressants and other anticholinergic drugs cause constipation, and how often?

For bladder antimuscarinics the pooled figure is clear: OR 2.18 (95% CI 1.82 to 2.60) versus placebo, with solifenacin highest at OR 3.02 and tolterodine lowest at 1.36. For tricyclics, the Cochrane review of amitriptyline reported any adverse event in 55% versus 36% on placebo (RR 1.5, NNH 5.2) but did not publish a separate constipation rate, so a precise figure for amitriptyline is not available from that review. (Source 3)

Are diuretics, antiepileptics and aluminium antacids really constipation causers?

They appear on a US government body's list of medicines that can make constipation worse, alongside calcium channel blockers and iron. We could not reach trial-level or meta-analytic rates for diuretics, antiepileptics or aluminium-containing antacids, so for those the evidence in this write-up is an agency position rather than a quantified rate. (Source 9)

References

1. The British Journal of Psychiatry. Clozapine-induced gastrointestinal hypomotility: presenting features and outcomes, UK pharmacovigilance reports, 1992–2017. 2022. DOI 10.1192/bjp.2022.24. Read the source
2. Digestion. Prevalence and Risk Factors of Constipation Symptoms among Patients Undergoing Colonoscopy: A Single-Center Cross-Sectional Study. 2024. PMID 38754395, DOI 10.1159/000539366. Read the source
3. Digestive Diseases and Sciences (structured abstract reproduced in the Database of Abstracts of Reviews of Effects, NCBI Bookshelf). Overactive bladder drugs and constipation: a meta-analysis of randomized, placebo-controlled trials. 2011. PMID 20596778. Read the source
4. BMC Medicine. Comparative risk of severe constipation in patients treated with opioids for non-cancer pain: a retrospective cohort study in Northwest England. 2025. PMID 40518524, DOI 10.1186/s12916-025-04118-7. Read the source
5. Pain and Therapy. Impact and Consequences of Opioid-Induced Constipation: A Survey of Patients. 2021. DOI 10.1007/s40122-021-00271-y. Read the source
6. International Journal of Molecular Sciences. Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis. 2016. PMID 27271593, DOI 10.3390/ijms17060863. Read the source
7. PLOS ONE. Ferrous Sulfate Supplementation Causes Significant Gastrointestinal Side-Effects in Adults: A Systematic Review and Meta-Analysis. 2015. PMID 25700159, DOI 10.1371/journal.pone.0117383. Read the source
8. PLOS ONE. Efficacy and safety of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials. 2017. PMID 28291778, DOI 10.1371/journal.pone.0172846. Read the source
9. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health. Symptoms & Causes of Constipation. 2026. Read the source
10. Office of Dietary Supplements, National Institutes of Health. Calcium – Health Professional Fact Sheet. 2026. Read the source
11. International Journal of Environmental Research and Public Health. Association between Drug Usage and Constipation in the Elderly Population of Greater Western Sydney Australia. 2018. DOI 10.3390/ijerph15020226. Read the source
12. Cochrane Database of Systematic Reviews. Amitriptyline for neuropathic pain in adults. 2015. DOI 10.1002/14651858.CD008242.pub3. Read the source