Not too long ago I came across a interesting case involving nausea and abdominal pain getting worse over the last 6 months in a patient. The symptoms started acutely out of nowhere and gradually got worse. Symptoms of nausea would be intermittent at first and then constant. Nausea would get worse with eating along with onset of abdominal pain. Several tests were performed with no abnormal findings. Of note, no gastric emptying test was performed. Even antiemetics were given without much improvement. After reviewing the case and the history, the only thing that changed in the patient was that starting doses of psychiatric medication were increased over several months. The medications administered by another specialist were Mirtazapine, Bupropion, and Guanfacine. These medications were being used to treat ADHD, Anxiety/Depression, and Insomnia. The mirtazapine dose was doubled in the 6 months, along with dose increases in Wellbutrin. It appeared symptoms worsened overtime with the dose increases per patients recall. Is it possible these medications have anything to do with the patients symptoms and worsening of their symptoms?

This is no means medical advice for anyone as every patient is different, but it is quite possible the dose increases may have contributed to this patients symptoms. First let’s take a look at the pharmacological properties of these medications.

1. Mirtazapine – Exact mechanism of action unknown, but thought to antagonize alpha-2 adrenergic and serotonin 5-HT2 receptors (increases noradrenaline and serotonin), has antihistamine effect (sedating effect is higher at lower doses).
2. Bupropion – Inhibits neuronal uptake of norepinephrine and dopamine (increases noradrenaline and dopamine), evidence it increases serotonin effect as well.
3. Guanfacine – Stimulates alpha-2 adrenergic receptors (increased noradrenaline effect).

In the patient above, the insomnia actually got worse when the higher mirtazapine dose was prescribed according to patients recall. This makes sense as the lower dose is better for insomnia as its antihistamine effect is less masked. At the higher dose, it has a higher noradrenaline response which tends to contribute to insomnia. In addition, Mirtazapine, Bupropion, and Guanfacine all contribute to increased noradrenaline response. Likewise, serotonin response can be increased by both Mirtazapine and Bupropion. So back to the question, how may this affect the patients gut function and could it be contributing to their symptoms?

Let’s take a look at the effect of Noradrenaline and Serotonin on the Gut. In the gut, the sympathetic nervous system and parasympathetic nervous system are at play with opposite effects. Noradrenaline acts on the sympathetic nervous system to delay gastric emptying and motility of the GI Tract. This increases gastric emptying time. On the other hand, serotonin buildup can lead to a condition called serotonin syndrome. Mild symptoms of serotonin syndrome include nervousness, nausea, vomiting, diarrhea. More serious symptoms include confusion, tachycardia, seizures, arrhythmias, syncope, and death.

Looking back at the patient’s initial presentation and progressive symptoms over months, is it possible that the patient was developing a insomnia from a higher amount of noradrenaline in their system? Were they having abdominal discomfort after eating with increased nausea from delayed gastric emptying and GI motility contributing to a medication induced gastroparesis? Was a possible elevation in serotonin contributing to a mild chronic serotonin elevation causing nausea? We suspected the above to be the possible culprit as nothing else was found to explain the sudden symptoms worsening over several months.

So, what did the patient do? Patient began to wean off the Bupropion with rapid improvement in the nausea and abdominal discomfort. The insomnia also resolved after going back to the lower dose of Mirtazapine almost overnight. Thus, you can see it is important to look closer at the psychiatric medication and dosing changes when there are unexplained new symptoms in a patient where the cause can’t be found. This is especially the case if they are experiencing symptoms of gastroparesis and nausea.

Disclaimer: This post is for informational purposes only and not to be used for medical advice.

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