Which drug is most likely to cause constipation? An Overview of Common Culprits

October 10, 2025 •

4 min read

According to the National Institutes of Health, opioid-induced constipation (OIC) affects a significant percentage of patients taking opioids, with some studies estimating the prevalence between 40% and 95%. This makes opioids the leading drug class most likely to cause constipation, but they are far from the only ones.

Quick Summary

Several drug classes, most notably opioids, can cause or worsen constipation by affecting the digestive system's motility and secretions. This guide explains how various medications impact bowel function and offers advice on managing these unwelcome side effects.

Key Points

Opioids are the most common cause: Opioid pain medications are most likely to cause constipation due to their direct action on receptors in the gut, which slows down intestinal movement and dries out stool.
Anticholinergics are significant culprits: Medications with anticholinergic effects, including some antidepressants and antihistamines, also commonly cause constipation by blocking nerve signals to the gut.
Calcium channel blockers slow digestion: Used for blood pressure, these drugs can relax the smooth muscles in the digestive tract, with certain types like verapamil being particularly problematic.
Iron supplements can irritate the bowels: Oral iron is known to cause constipation, potentially by irritating the intestinal lining or altering the gut microbiome.
Proactive management is key: For those taking constipating medications, especially opioids, a combination of dietary changes, increased hydration, and specific laxatives is often necessary for management.
Consult a healthcare professional: Never stop a medication on your own due to constipation. A doctor can recommend dosage adjustments, alternative drugs, or specialized treatments.

What is Medication-Induced Constipation?

Constipation is defined by the Rome III criteria, which includes straining, hard stools, a sensation of incomplete evacuation, and reduced frequency of bowel movements. Many medications can interfere with the normal function of the digestive system, leading to or exacerbating this condition. The severity can range from mild inconvenience to serious health problems like fecal impaction and bowel obstruction. Understanding which drugs pose the highest risk is the first step toward effective management and prevention.

The Primary Culprit: Opioid Pain Medications

Opioid pain relievers, such as morphine, oxycodone, and codeine, are the most frequent and well-recognized cause of medication-induced constipation. This condition, known as opioid-induced constipation (OIC), is a direct result of how these drugs interact with the gastrointestinal (GI) system.

The Mechanism of Action

Binding to Receptors: Opioids bind to μ-opioid receptors found throughout the GI tract.
Slowing Motility: This binding reduces intestinal muscle contractions (peristalsis), which slows the movement of stool through the bowels.
Decreasing Secretions: Opioids decrease the amount of fluid and mucus secreted into the intestines.
Increasing Absorption: With slowed transit, more water is absorbed from the stool, making it harder and drier.
Affecting Sphincter Tone: They increase the tone of the anal sphincter, impairing the reflex for defecation.

Unlike the analgesic effects of opioids, tolerance to their constipating effects does not typically develop, meaning the issue persists as long as the medication is taken. This is why patients on long-term opioid therapy are often advised to start a laxative regimen proactively.

Other Drug Classes That Cause Constipation

While opioids are the most potent offenders, several other medication classes can also significantly impact bowel regularity.

Anticholinergic Drugs

This broad category includes medications for conditions like overactive bladder, allergies, and psychiatric disorders. By blocking the neurotransmitter acetylcholine, these drugs disrupt the nervous signals that control muscle movement and secretions in the gut, slowing things down.

Examples: Diphenhydramine (Benadryl), oxybutynin (Ditropan), and tricyclic antidepressants (amitriptyline).

Calcium Channel Blockers

These medications are used to treat high blood pressure and other heart conditions. They work by relaxing the smooth muscles in blood vessels, but this relaxing effect can also extend to the smooth muscles of the digestive tract.

Examples: Verapamil and diltiazem are particularly known for this side effect, with verapamil having a notably strong impact.

Iron Supplements

Prescribed for anemia, oral iron supplements are a well-known cause of digestive upset, including constipation. The mechanism is complex but involves several factors, including oxidative stress and changes to gut bacteria.

Management Tip: Consider different formulations or intravenous iron if oral options are intolerable.

Antidepressants and Antipsychotics

In addition to tricyclic antidepressants' anticholinergic effects, some SSRIs like paroxetine and certain antipsychotics, notably clozapine and olanzapine, can cause constipation. In the case of clozapine, severe gastrointestinal issues can be fatal, prompting an FDA warning.

Other Medications

Diuretics: By removing fluid from the body, they can cause dehydration and lead to harder, drier stools.
Antacids with Calcium or Aluminum: These ingredients can directly slow muscle contractions in the gut.
NSAIDs: Some nonsteroidal anti-inflammatory drugs like ibuprofen have also been linked to constipation, particularly with high or regular use.

Comparison of Major Constipating Drugs


Drug Class	Examples	Primary Mechanism	Management Considerations
Opioids	Morphine, Oxycodone, Codeine	Inhibits gut motility and secretions via μ-opioid receptors.	Prophylactic stimulant/osmotic laxatives are often required; bulk-forming agents not recommended.
Anticholinergics	Diphenhydramine, Oxybutynin	Blocks acetylcholine, reducing gut muscle movement and secretions.	Consider alternative therapies; increase fluid and fiber intake.
Calcium Channel Blockers	Verapamil, Diltiazem	Relaxes smooth muscle in the GI tract, slowing digestion.	Adequate fiber and fluid intake; sometimes switching to a less constipating agent (e.g., amlodipine) helps.
Iron Supplements	Ferrous sulfate, Ferrous gluconate	Irritates gut, alters microbiome, and increases water absorption.	Try slow-release formulations; increase fiber and fluid; take with vitamin C to aid absorption.
Antidepressants (TCAs)	Amitriptyline	Potent anticholinergic effects reduce peristalsis.	Discuss switching to a less-constipating agent with a doctor.

Strategies for Managing Medication-Induced Constipation

If you are taking a medication known to cause constipation, there are several steps you can take to alleviate the problem. Always consult your healthcare provider before stopping or altering a prescribed medication.

Increase Fiber Intake: Incorporating more high-fiber foods such as fruits, vegetables, beans, and whole grains into your diet can help. However, be cautious with bulk-forming fiber supplements (e.g., psyllium) if on opioids, as they may cause obstruction.
Stay Hydrated: Drinking plenty of water is essential, as it helps soften stools and aids bowel regularity.
Regular Exercise: Physical activity stimulates bowel muscles and can help keep things moving. Even moderate activity like walking can be beneficial.
Consider Over-the-Counter Laxatives: Different types of laxatives work in different ways:
- Osmotic Laxatives: Polyethylene glycol (Miralax) and magnesium hydroxide (Milk of Magnesia) draw water into the colon to soften stool.
- Stimulant Laxatives: Senna and bisacodyl cause the intestinal muscles to contract. These are often recommended with opioids.
Address Specific Causes: For opioid-induced constipation, standard laxatives may not be enough. Newer prescription medications like peripherally acting μ-opioid receptor antagonists (PAMORAs) specifically counteract the opioid effect in the gut without affecting pain relief.

Conclusion

While many medications can lead to constipation, opioid pain relievers are most likely to cause this significant and persistent side effect due to their direct impact on intestinal motility and secretions. Other major contributors include anticholinergics, calcium channel blockers, and iron supplements, all acting through distinct pharmacological mechanisms. The key to managing drug-induced constipation lies in understanding the cause and working with your healthcare provider to implement targeted interventions. Don't stop taking a prescribed medication abruptly without consulting a professional, as there are many effective strategies to relieve symptoms while continuing your necessary treatment. Further information can be found on resources like the Drugs.com medical answers page.

Frequently Asked Questions

Opioids bind to μ-opioid receptors in the intestinal tract, which directly reduces muscle contractions (peristalsis) and decreases fluid secretions into the bowel. This results in slow-moving, hard, and dry stools that are difficult to pass.

While increasing dietary fiber is generally recommended for constipation, it is often not sufficient for medication-induced constipation, especially OIC. With opioids, bulk-forming fiber can even worsen the problem if gut motility is severely slowed. In these cases, laxatives are usually necessary.

The best laxative depends on the medication causing the issue. For OIC, a stimulant laxative like senna or an osmotic laxative like polyethylene glycol is often recommended. Always check with your doctor or pharmacist for a specific recommendation.

It might. Certain classes of blood pressure medications, particularly calcium channel blockers like verapamil and diltiazem, can relax the smooth muscles of the intestines, leading to constipation.

If you suspect an antidepressant is causing constipation, speak with your doctor. They may suggest lifestyle changes or recommend a different medication with a lower risk of this side effect, such as switching from a tricyclic to a less constipating SSRI.

Yes. When standard laxatives fail to work, your doctor may prescribe specific medications for OIC called peripherally acting μ-opioid receptor antagonists (PAMORAs), such as methylnaltrexone (Relistor) or naloxegol (Movantik).

No, you should never stop a prescribed medication without first consulting your healthcare provider. Abruptly stopping some medications can be dangerous. A doctor can help you safely manage the side effects or transition to an alternative.