Psychotropics and Gastrointestinal Conditions: Prescribe with the Gut in Mind

Last updated: December 15, 2018

Host: Wegdan Rashad, MD

Here is a summary of this episode:

  • Always ask about over-the-counter drugs like antacids, antiemetics and spasmolytics as they may interfere with drug absorption.
  • In patients who have undergone gastric bypass, use immediate release formulations, or give liquid form of drugs.
  • There is evidence to suggest that IBS-constipation responds better to SSRIs and IBS-diarrhea to TCAs.
  • The risk of GIT bleeding with SSRIs is 1.5 to 2 times greater. Patients with a defect in platelet number or function and those who H. pylori infection are at greater risk.


Hello everyone and welcome to the Psychopharmacology Institute podcast. I’m your host, Dr. Wegdan Rashad. In this series we will be discussing topics that matter to you, the mental health clinician, in your practice, sharing expert opinions and the latest research.

Today we will learn about prescribing psychotropics with the gut in mind. In the first part we will discuss how GI disease can affect your prescribing and in the second half, how psychotropics can affect our GIT. It is quite an intimate relationship, and we have Dr. James Levenson as our guiding expert. Dr. Levenson is a Professor of Psychiatry and Department Chair of Consultation-Liaison at the Virginia Commonwealth University School of Medicine.

So if you’re ready, put your seatbelts on and let’s start!

It doesn’t take many years of psychiatry practice to realize that GI symptoms are very common in our patients. While some patients mention it, others don’t and decide to take over the counter medications to relieve their symptoms. My question is, how can common GI ailments and their OTC medications affect the drugs we may be prescribing? Over to Dr. Levenson.

Dr. Levenson:
Many patients are taking antacids over the counter. Sodium-containing antacids like Alka-Seltzer are going to increase lithium excretion just like any other increase in sodium intake. When antacids increase gastric pH by neutralizing gastric acid, this increases the absorption rate for enteric-coated tablets like enteric-coated valproic acid. Patients with nausea and vomiting are often given antiemetics like prochlorperazine or promethazine. Patients with gastroparesis are often given metoclopramide. And it’s important to remember that these drugs are dopamine antagonists just like antipsychotics. And they carry the same risk of extrapyramidal disorders including tardive dyskinesia if given chronically and neuroleptic malignant syndrome. And so the risk will be greater if they’re administered alongside typical or atypical antipsychotics. Many GI patients are taking anticholinergic, antispasmodics. And many of our drugs, our psychotropics are anticholinergic. The combination of multiple anticholinergic drugs, of course, increases the risk for confusion and delirium or even just subtle cognitive impairment especially in the elderly.

So, remember to ask about OTC drugs patients may be taking like sodium-containing antacids, antiemetics, and antispasmodics and adjust their psychotropics accordingly.

Sometimes, we would need to reconsider the formulation of medication we use. Over to Dr. Levenson.

Dr. Levenson:
Most GI diseases increase motility of the intestinal tract. And by doing so, they tend to reduce both oral and rectal absorption of drugs because the drugs are not spending as much time in contact with the intestinal surface. Therefore, in such patients, where possible, one should consider liquid or orally disintegrating tablets because they’re more likely to be completely absorbed. This is particularly a concern for patients who have conditions in which small bowel absorption is reduced and a reason to avoid extended-release formulations. That capsule may never dissolve at all as it’s rushed along.

Ok, another scenario. You have a patient who is being treated for major depressive disorder and who recently underwent gastric bypass surgery for morbid obesity. By gastric bypass, I mean a procedure like a Roux-En-Y that bypasses the stomach, duodenum, and part of the proximal jejunum.What changes do we need to make to his medications?

Dr. Levenson:
Well, what is clear is that one should avoid slow release preparations and where possible always choose immediate release forms or even better, crushed tablets or liquid forms of psychotropic drugs. I’ve had some post-bariatric surgery patients where the only way I could get clinical benefit from an antidepressant or an antipsychotic was administering it as a liquid. At the same time, if the patient experiences significant weight loss, this will usually mean the need to reduce the dose of a lipophilic drug which is most of our drugs because the volume of distribution of those drugs is reduced as there’s less and less body fat. And we also have to keep in mind that many patients after bariatric surgery have a lot of vomiting for the first two or three months. And of course, the drug vomited up will not be absorbed.

So, use immediate release formulations, crush tablets or give liquid form of drugs. Also, we might have to reduce the dose of lipophilic drugs and be mindful of vomiting in the first postoperative months.
The question comes to mind, what other ways can we administer an antidepressant, other than orally, if it proves too difficult?

Dr. Levenson:
In the United States and Canada, there are no approved parenteral formulations of antidepressants. Intravenous citalopram and several tricyclics including clomipramine are available in Europe but not in North America. Rectal suppositories, while not FDA approved, of several tricyclics and trazodone have been reported in case studies and general bioavailability has been less than oral administration which is not surprising. Some clinicians have reported using mirtazapine orally dissolving tablets by having the patient hold it under their tongue but there are little data available as to how effective that absorption is. There have also been case reports of sublingual absorption of fluoxetine oral solution but that requires a very cooperative patient to hold the liquid under his or her tongue long enough.
The only alternate routes for an antidepressant drug that are approved in the United States are the transdermal route for selegiline and the sublingual route for selegiline which the United States approved for Parkinson’s disease but in theory, could be used to treat a depressed patient.

Very interesting! I personally have never used antidepressants in any route other than orally, but while we’re on the topic of alternative routes of administration, what about other classes?
As you may already know, antipsychotics can be given in parenteral, sublingual and orally disintegrating forms. You may also be interested to know that quetiapine is probably absorbed intranasally as well. We know this from people who snort quetiapine for recreational use.
Dr. Levenson now talks a bit about alternative routes of benzo administration.

Dr. Levenson:
In contrast to antidepressants, benzodiazepines can be given by many different alternate routes. Diazepam, lorazepam, and midazolam are approved in the United States and Canada for both intravenous and intramuscular administration although I do not recommend using diazepam intramuscularly because absorption is actually somewhat unpredictable and erratic. Rectal administration of diazepam is approved in the United States and Canada and is typically used to terminate status epilepticus but could be used for managing anxiety when necessary. Zolpidem is available in an approved sublingual form in the United States. But beyond the approved routes, benzodiazepines appear generally to be well absorbed sublingually. And while the absorption is slower that way than giving it intramuscularly, absorption of the benzodiazepine ultimately seems to result in similar bioavailability. A number of different benzodiazepines have been studied for rectal administration. Absorption is pretty rapid but erratic and unpredictable. Intranasal lorazepam has been studied and intranasal midazolam is in development. The Z hypnotics have not been studied for non-oral routes.

So we spoke about how common GI medications affect pharmacokinetics, tips for prescribing in patients with gastric bypass surgery and then spoke a bit about alternative routes of administration in patients who cannot tolerate taking medications orally.
Alright, now that concludes the first part of this podcast, now let’s move on to the second part which is how psychotropics can affect the GIT.

Stay tuned!

If I were to announce a pop quiz to ask you to list 5 GIT side effects of psychotropics, I’m sure you could come up with even more than 5, because our beloved psychotropics are notorious for GI adverse effects. But they’re not always bad, let’s look at the bright side and first explore how antidepressants can treat a GI condition, commonly known as IBS or irritable bowel syndrome.

Dr. Levenson:
Now, irritable bowel is generally divided into three types, diarrhea-predominant IBS, constipation-predominant IBS and patients who have a mixture of both diarrhea and constipation as their symptoms. There has not been sufficient study regarding whether these subtypes would respond differently to different antidepressants. And there’s been insufficient study of how much the presence of comorbid anxiety or depression might influence the response. Bottom line, which comes partly from all the data in these studies and partly from practical experience is that patients with constipation-predominant irritable bowel syndrome have a good chance of benefiting from an SSRI, while patients with diarrhea-predominant irritable bowel syndrome are likely to benefit from tricyclics. And conversely, I would generally avoid giving a tricyclic to a constipation-predominant IBS patient and I would avoid giving an SSRI to a diarrhea-predominant IBS patient since they may respectively aggravate the patient’s symptoms.

Today’s mantra for me will be, “If IBS-constipation, give SSRI. If IBS-diarrhea, give TCA” and repeat!

Oh, I can read your mind right now. You’re probably thinking, if it works, then it’s because it treats the co-morbid anxiety or mood disorder. Or maybe it’s placebo. I thought the same, but thankfully we have our curious expert consultations host, Dr. Dana Wang to ask those big questions!

Dr. Wang:
Do you think the effectiveness of tricyclic antidepressant or SSRI for irritable bowel syndrome is primarily through the placebo effect or is it also through treating any underlying anxiety or depressive symptoms?

Dr. Levenson:
Many patients with irritable bowel syndrome have comorbid anxiety or affective disorders which in turn, are aggravating their bowel dysfunction, and the treatment with an antidepressant in alleviating the psychiatric symptoms then indirectly alleviates irritable bowel. But that’s not the only mechanism of their effectiveness. There have been numerous randomized controlled trials that have shown that antidepressants are effective in irritable bowel syndrome patients even in the absence of diagnosable psychiatric pathology. So there is some effect—we don’t understand exactly what it is—presumably on the enteric nervous system in which antidepressants are benefiting patients with IBS. The placebo effect is a positive influence even for a clinically active drug. It helps if patient and physician both believe the drug is going to be helpful. Conversely, if either the patient or the physician are very doubtful or skeptical that a drug can help, it can interfere with the physiologically derived benefits from the drug.

Thank you, Dr. Wang. You can listen to the full interview where she asks many more curious questions. The interview is available for our premium members on,

This podcast would not be complete without mentioning one of the scary GI-related adverse effects of SSRIs. Can you guess?

Yes, it is the risk of GI bleeding with SSRIs. You may already be cautious when it comes to prescribing nonsteroidal anti-inflammatory drugs with SSRIs, but what does the evidence say? Just how likely is GI bleeding in patients taking SSRIs?

Dr. Levenson:
There have been many studies, the data vary but there does seem to be a 1.5 to doubling increase in the relative risk but the absolute risk of a gastrointestinal hemorrhage remains small. The risk is increased with concomitant nonsteroidal anti-inflammatory drugs. Caution is advised in patients who are taking multiple drugs that can impair platelets. And what I would call high-risk patients are those patients with marked thrombocytopenia, for example, a platelet count under 25,000. Patients with that low a platelet count are at risk for spontaneous bleeding. And I would also urge caution in the prescription of SSRIs in patients who have a normal number of platelets but who have dysfunctional platelets like in the inherited disorder Von Willebrand disease. The risk of GI bleeding with SSRIs is also increased in patients who are infected with Helicobacter pylori. And we should mention that there are rare cases of SSRIs themselves causing thrombocytopenia.

So generally, the risk is small, but we need to keep a close eye on those taking NSAIDs and I should add, this applies to patients who take high and sustained doses of NSAIDS mainly, not the occasional ibuprofen user. Also, watch out for those who already have a bleeding diathesis and those with H. pylori infection.

I would highly recommend you watch Dr. Levenson’s full lecture on our website for more.

Wonderful! And that concludes our journey with the gut in mind. But please keep your seatbelts on for the upcoming… key points!

Key Points

  • Always ask about over-the-counter drugs like antacids, antiemetics, and spasmolytics as they may interfere with drug absorption.
  • In patients who have undergone gastric bypass, use immediate release formulations, or give liquid form of drugs. And keep in mind the dose and their weight loss.
  • Consider alternative routes of administration if patients cannot take medications orally.
  • There is evidence to suggest that irritable bowel syndrome responds well to antidepressants. IBS-constipation responds better to SSRIs and IBS-diarrhea, TCAs.
  • The risk of GI bleeding with SSRIs is 1.5 to 2 times greater. Patients with a defect in platelet number or function and those with H.pylori infection are at greater risk.

Liked our podcast? Visit us at where you can find more podcasts and some lectures absolutely free. You can choose to become a premium member to access all lectures and interviews. Also, we would be thrilled to hear from you, drop us an email at

The following people participated in this episode: Dr. Flavio Guzman as the general editor, Rosario Anon Suarez as the audio engineer, Pamela Gonzalez as the project manager and myself, Dr. Wegdan Rashad as the host. We’d also like to thank Dr. James Levenson and Dr. Dana Wang, for being with us.

Thank you for joining us in today’s podcast until the next episode, goodbye!


  1. Ruepert, L., Quartero, A. O., de Wit, N. J., van der Heijden, G. J., Rubin, G., & Muris, J. W. (2011). Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev, 8.
  2. Laporte, S., Chapelle, C., Caillet, P., Beyens, M. N., Bellet, F., Delavenne, X., … & Bertoletti, L. (2017). Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: a meta-analysis of observational studies. Pharmacological research, 118, 19-32.
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