The Use of Psychotropics in Irritable Bowel Syndrome and Bariatric Surgery
James L. Levenson, M.D.
Virginia Commonwealth University
- In patients with irritable bowel syndrome (IBS):
- Constipation-predominant IBS may benefit from SSRIs
- Diarrhea-predominant IBS may benefit from TCAs
- In patients who undergo gastric bypass surgery:
- Avoid XR preparations, instead preferring IR forms, crushed tablets, and liquid forms
- Significant weight loss will usually mean a need to reduce the dose of lipophilic drugs
Our next topic is the use of psychotropic drugs in gastrointestinal diseases.
Patients whose gastrointestinal disease results in chronic malabsorption such as pancreatitis, inflammatory bowel disease, patients with gastric bypass predictably are going to have some difficulties in absorbing most psychotropic drugs.Patients with delayed gastric emptying like patients with diabetic gastroparesis are going to be more subject to worsening of their medical condition if they’re given an anticholinergic drug and may have difficulty absorbing some psychotropic drugs because of increased exposure to gastric acid in a gastroparetic patient. In patients with gastrointestinal problems causing constipation, of course we should avoid anticholinergic drugs.
What’s the role of antidepressants in the treatment of irritable bowel syndrome? This is an important question which I think has been overlooked by many gastroenterologists. In 2011, Cochrane review concluded that there was actually good evidence that antidepressants are effective in the treatment of irritable bowel syndrome. They went on to state that the subgroup analyses for SSRIs and tricyclics are unequivocal but their effectiveness may depend or vary with individual patients. That’s one systematic review. But in fact, every other meta-analysis that has been published and there have been quite a few of them in the last decade has concluded that tricyclics and SSRIs are beneficial in irritable bowel syndrome even if the patient does not have an affective or anxiety disorder.
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. There’s really quite limited data regarding SNRIs, benzodiazepines and other psychotropics. The 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.
Another important clinical question is: How is drug absorption affected after gastric bypass surgery? This is clinically important because antidepressants are the most commonly used medication class found in bariatric surgery patients prior to operation. So what we’re talking about here is gastric bypass surgery not restrictive procedures like a gastric sleeve but instead procedures like a Roux-En-Y that bypass the stomach and bypass the duodenum and part of the proximal jejunum. This kind of surgery has complex effects potentially on absorption. The reduction in exposure to gastric acid because the stomach is largely bypassed will reduce the solubility of some drugs which will make it harder to absorb them. On the other hand, that increase in pH may increase the absorption of weak bases which is most of our drugs. The fact that the duodenum is bypassed as well as part of the jejunum will reduce exposure to the intestinal surface where most drug absorption occurs and this will tend to reduce absorption of many drugs. There are also some complex effects from change in exposure to cytochrome enzymes 3A4 and P-glycoprotein in the gut wall and also changes in first pass metabolism.
What practically can we conclude? 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.
But ultimately, what do we know about how effectively drugs are absorbed after gastric bypass surgery? Multiple reviews have unfortunately concluded we still know very little at least based on data. Studies of SSRIs and SNRIs that have been published include very small numbers of patients. What they found was most but not all had a significant decrease in absorption during the weeks postoperatively. On the other hand, there are two case reports of lithium toxicity after gastric bypass surgery. There is no published information on the absorption of other antidepressants like tricyclics or bupropion, mirtazapine or trazodone. There’s no published information on benzodiazepines except for one single dose study. No published information on antipsychotics, valproate, lamotrigine or stimulants.
So what are some key take home points regarding how drug absorption is affected after gastric bypass surgery? Drug absorption is likely to be reduced in many but not all patients. One should avoid slow release preparations and instead prefer immediate release forms, crushed tablets or liquids. And keep in mind that if the patient loses a large amount of weight you’ll probably need to reduce their dose of a lipophilic drug. And most of our drugs are lipophilic. That’s how they get into the brain by crossing the blood-brain barrier.
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Also, you can access to the original version in Spanish: “Uso de psicotrópicos en alteraciones gastrointestinales: intestino irritable y cirugía gástrica”
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