Mirtazapine For Treatment-Resistant Gastroparesis

Gastroparesis is a condition of abnormal gastric motility characterized by delayed gastric emptying without evidence of mechanical outlet obstruction. Symptoms, which include nausea, vomiting, postprandial fullness, early satiety, and abdominal discomfort, are present in approximately 7%–15% of the population Now comes a report on the successful use of mirtazapine for the treatment of severe gastroparesis refractory to conventional measures.

A 27 year-old woman with type I diabetes mellitus and tripathy was referred for treatment of depression associated with uncontrolled nausea and vomiting. Upper gastrointestinal endoscopy had revealed mild hemorrhagic gastritis, multiple shallow duodenal ulcers, and a 2-cm hyperplastic mucosal polyp on the posterior wall of the gastric antrum, but no specific outlet obstruction. Prokinetics, including 500 mg to 1,500 mg of erythromycin, 100 mg of itopride, and 10 mg of intravenous (IV) metoclopramide were administered for over a month, but failed to relieve the postprandial discomfort, nausea, and vomiting. The patient continued to exhibit a markedly delayed gastric-emptying time of 619 minutes (normal limit = 90 minutes).

One month before referral, 200 U of botulinum toxin had been injected into the pylorus. Initially, gastric symptoms improved, as demonstrated by a gastric emptying time of 70 minutes. However, approximately 10 days post-injection, nausea and vomiting reappeared and worsened. A follow-up endoscopy showed a large quantity of food still in the stomach after a 16-hour fast, suggesting the recurrence of delayed gastric emptying. For the next 7 days, oral intake, except for oral medications with water, was disallowed while TPN was initiated. While vomiting resolved, intermittent nausea persisted. When a liquid diet was reintroduced, vomiting and abdominal bloating recurred and worsened.

Next, the patient was referred for management of her depression. She had been suffering from depressed mood, diminished interest, inactivity, suicidal ideation, sleep disturbances (she had required 2 mg of IV lorazepam to induce sleep for 2 months), and poor appetite. Her depressed mood reportedly fluctuated with the severity of the nausea and vomiting. At the time of consultation, she had been receiving 1,500 mg of oral erythromycin, 2 mg of IV lorazepam, 10 mg of IV metoclopramide, and scored 25/60 on the Montgomery-Asberg Depression Rating Scale (MADRS) and 29/45 on the Gastroparesis Cardinal Symptom Index (GCSI).

Mirtazapine 15 mg QHS was initiated. The next day, nausea and vomiting were subjectively reduced by 30%, and IV lorazepam and metoclopramide were discontinued. Gastric symptoms resolved gradually, and, within 7 days, the patient could eat solid foods, had a GCSI score of 0, and gastric emptying time of 69 minutes. Within a few days after starting mirtazapine, sleep disturbances and agitation resolved, while other depressive symptoms fully recovered (MADRS score: 0). The patient was subsequently discharged and remained symptom-free over the next 3 months of follow-up.

Severe refractory symptoms associated with multiple hospitalizations are encountered in 2%–5% of gastroparesis patients. When depression is comorbid with gastroparesis, mirtazapine is certainly a medication worth considering. Its utility for severe, refractory gastroparesis uncomplicated by depression is a question worthy of further study.

Disclosure: Dr. Ginsberg is a speaker for AstraZeneca, Cyberonics, Forest, and GlaxoSmithKline; and has received research support from Cyberonics.

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