Concerns Taking Motegrity With Psych Medication

In our latest question and answer, the pharmacist discusses the psychiatric concerns with Motegrity.


I've just been prescribed Motegrity and learned about its serious psychological side effects. I've been taking antidepressants, mood stabilizers, and anti-anxiety medications for a while. Would those help in preventing Motegrity's psychological side effects?

Asked by Marcy On May 18, 2024

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published May 19, 2024
Last updated Jun 14, 2024

Key points

  • Motegrity (prucalopride), used for chronic idiopathic constipation, has been linked to suicidal ideation and behavior, requiring careful monitoring, especially for those on psychiatric medications, due to its action on serotonin (5-HT4) receptors; alternative medications like Linzess may be considered, and it's essential to consult with your doctor.

Hello and thanks for your question!

You are correct that Motegrity has been associated with suicidal ideation and behavior. In fact, it has a warning for this in the drug labeling:

Suicidal Ideation and Behavior: Monitor patients for persistent worsening of depression and emergence of suicidal thoughts and behavior. Instruct patients to discontinue MOTEGRITY immediately and contact their healthcare provider if their depression is persistently worse, or they experience emerging suicidal thoughts or behaviors.
Motegrity Prescribing Information

This warning exists based on the mechanism of action of Motegrity and the results of clinical trials, as reported in the prescribing information:

In the double-blind trials, one patient reported a suicide attempt 7 days after the end of treatment with MOTEGRITY 2 mg once daily; none were reported in patients on placebo. In the open-label trials, two patients reported a suicide attempt and another patient reported suicidal ideation. Completed suicide was reported in two patients, previously treated with MOTEGRITY 2 mg or 4 mg; both discontinued MOTEGRITY for at least one month prior to the event.
Motegrity Prescribing Information

Although a definitive causal relationship has not been established, these reports have led to important safety warnings. Additionally, safety warnings are present based on the fact that Motegrity affects certain serotonin receptors.

How Motegrity Works

Motegrity (prucalopride), a selective serotonin type 4 (5-HT4) receptor agonist, is primarily used to treat chronic idiopathic constipation.

Serotonin (5-HT4) receptors play a key role in starting the process of peristalsis, which is the wave-like muscle contractions that move food through the digestive tract. Motegrity specifically targets 5-HT4 receptors with high specificity, without significantly affecting other serotonin receptors like 5-HT2A, 5-HT2B, and 5-HT3.

Although Motegrity is selective for 5-HT4 receptors, these receptors are also present in the central nervous system (CNS).

5-HT4 receptors in the CNS are involved in various neurological processes, including the regulation of mood, anxiety, and cognitive function. By stimulating these receptors, Motegrity may alter the balance of neurotransmitters, such as increasing the release of serotonin and dopamine. Changes in these neurotransmitters can potentially affect mood and behavior.

This is why the use of Motegrity requires careful monitoring for any signs of worsening depression or emerging suicidal thoughts and behaviors, especially in patients who are already taking other psychiatric medications.

Other drugs that affect 5-HT4, such as Zelnorm, used for irritable bowel syndrome, have similar warnings regarding suicidal behaviors.

Additional Thoughts

There isn't enough data to determine whether taking other psychiatric medications such as antidepressants, mood stabilizers, and anti-anxiety medications, like you mentioned in your question, could potentially increase or decrease the risk of experiencing psychiatric problems when taking Motegrity (prucalopride), since we don't even know if a causal relationship exists between Motegrity and psychiatric problems.

Nevertheless, since Motegrity does affect a certain type of serotonin receptor, it stands to reason that you should take extra care if you are taking other drugs that affect serotonin.

There are several options for gastrointestinal drugs that don't affect serotonin, like Linzess. This could be a potential option for you.

I highly recommend talking to your doctor to determine the best course of treatment for your medication situation.

Thanks for reaching out!


  • An overview of the efficacy and safety of prucalopride for the treatment of chronic idiopathic constipation, PubMed
  • Motegrity Prescribing Information, PubMed
  • Neurological and psychiatric adverse events with prucalopride: case report and possible mechanisms, PubMed

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Dr. Brian has been practicing pharmacy for over 13 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical, program development, and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Dr. Brian Staiger also has herbalist training and educational certificates in the field of medical ethnobotany. Feel free to send him an email at [email protected]! You can also connect with Dr. Brian Staiger on LinkedIn.

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