Use of Mirtazapine and Olanzapine in the Treatment of Refractory Hyperemesis Gravidarum: A Case Report and Systematic Review

Abstract

Hyperemesis gravidarum (HG) is a rare condition (1.1%) characterized by excessive vomiting, malnutrition, dehydration, and laboratorial alterations. Herein, we describe the even rarer and serious presentation of refractoriness to the usual treatment of antiemetics and parenteral nutrition, with improvement only after the use of olanzapine and mirtazapine. Two subsequent pregnancies of the same woman with HG are described, which were associated with severe weight loss, anemia, hyponatremia, hypokalemia, and mild dysfunction of liver enzymes. In the third pregnancy, the usual treatment for HG was not successful, requiring enteral nutrition and the introduction of olanzapine. In the fourth pregnancy, the patient refused to use enteral nutrition for refractory HG. Hence, the patient was started on mirtazapine at an initial dose of 15 mg/day, which was gradually increased to 30 mg/day. The patient responded well to the new regimen, as demonstrated by the decrease in symptoms, the gain of 10 kg in the pregnancy, and delivering a healthy newborn. A systematic review of literature showed 11 articles and 30 cases that successfully used mirtazapine in HG. Good clinical outcomes were seen with 4 days of the treatment and at an initial dose of 15 mg/day. However, most of these reports were from psychiatric profiles, with a predominance of depression and anxiety symptoms, and a poor description of the obstetric conditions and the disease progression itself. Pulmonary hypertension was described in one case and neonatal hyperexcitability in another. The case described in this paper reinforces the idea that mirtazapine and olanzapine can be considered in refractory HG, with good results. In the world literature, this is the second case of HG that has been successfully treated with olanzapine and the first in Latin America treated with mirtazapine.

Inpatient Management of Hyperemesis Gravidarum

“…In refractory cases in which standard pharmacotherapeutic treatments are ineffective, the use of psychiatric drugs such as olanzapine and mirtazapine has been proposed. 32…”

“…Antagonism of H1 receptors causes antihistaminergic activities, which results in antidepressive effects, helps with insomnia, and augments the anxiolytic effects caused by blockage of 5HT2 receptors. 30,32,34 H1 receptor antagonism also can result in weight gain by stimulating the appetite, which is common with antidepressants in general. 32,35 Mirtazapine's antiemetic and weight-gain effects, in addition to its role as an antidepressant and anxiolytic, make it a reasonable option for management of refractory cases of hyperemesis gravidarum, especially with co-existing depression or anxiety.…”

“…30,32,34 H1 receptor antagonism also can result in weight gain by stimulating the appetite, which is common with antidepressants in general. 32,35 Mirtazapine's antiemetic and weight-gain effects, in addition to its role as an antidepressant and anxiolytic, make it a reasonable option for management of refractory cases of hyperemesis gravidarum, especially with co-existing depression or anxiety. The use of mirtazapine was first reported in 2001 in a case series of seven patients with hyperemesis gravidarum and anxiety or depression comorbidities.…”

“…Antagonism of H1 receptors causes antihistaminergic activities, which results in antidepressive effects, helps with insomnia, and augments the anxiolytic effects caused by blockage of 5HT2 receptors. 30,32,34 H1 receptor antagonism also can result in weight gain by stimulating the appetite, which is common with antidepressants in general. 32,35…”

“…30,32,34 H1 receptor antagonism also can result in weight gain by stimulating the appetite, which is common with antidepressants in general. 32,35…”