What is the mechanism of action of this treatment?

Common treatments for morning sickness work through various mechanisms to alleviate symptoms. Mirtazapine, for example, increases norepinephrine and serotonin release by antagonizing central presynaptic alpha-2 adrenergic receptors, which can help reduce nausea and stabilize mood. Antihistamines like doxylamine block histamine receptors to mitigate nausea, while vitamin B6 (pyridoxine) aids in neurotransmitter synthesis and function. Understanding these mechanisms helps in choosing the most effective treatment tailored to the patient's needs.

What side effects are associated with this type of intervention?

Mirtazapine, used for severe nausea and vomiting in pregnancy, can cause side effects such as weight gain, sedation, and changes in appetite due to its action on 5-HT-2 receptors and presynaptic adrenergic alpha-2 receptors. Other common treatments for morning sickness include antihistamines like doxylamine, which may cause drowsiness and dry mouth, and vitamin B6, which is generally well-tolerated but can cause mild gastrointestinal upset. Ondansetron, another antiemetic, may lead to constipation and headaches. It is important to discuss these options and their potential side effects with a healthcare provider.

What prior FDA approvals exist?

The FDA has approved several treatments for morning sickness, including doxylamine-pyridoxine (Diclegis), which combines an antihistamine with vitamin B6. Other commonly used treatments include ondansetron, a serotonin 5-HT3 receptor antagonist, and metoclopramide, a dopamine antagonist. While mirtazapine, an antagonist of central presynaptic alpha-2 adrenergic receptors, is being studied for severe nausea and vomiting in pregnancy, it is not yet FDA-approved for this indication. These treatments differ in their mechanisms but aim to alleviate nausea and vomiting symptoms.

What other types of research exist?

Promising alternatives to mirtazapine for treating morning sickness in 2024 include GR38032F (a 5-HT3 receptor antagonist), gabapentin, ondansetron, metoclopramide, and zacopride. These options have demonstrated efficacy in managing nausea and vomiting in clinical studies.

← Back to Search

Antidepressant

Mirtazapine for Morning Sickness (ESNAP Trial)

Phase 1 & 2

Waitlist Available

Led By Katherine L Wisner, M.D., M.S.

Research Sponsored by Northwestern University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be between 18 and 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up weekly for three weeks

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial tests mirtazapine, a depression medication, for pregnant women with severe nausea and vomiting unresponsive to standard treatments. It works by stopping brain signals that make you feel sick. Mirtazapine is an antidepressant that has been shown to reduce nausea and vomiting in various clinical settings.

Who is the study for?

This trial is for English-speaking pregnant women experiencing severe nausea and vomiting that hasn't improved with standard treatments. They must have a specific score indicating moderate to severe symptoms, normal blood pressure, a healthy heart rhythm, be able to take an oral tablet at bedtime, and have a single pregnancy.

What is being tested?

The E-SNAP trial is testing the drug Mirtazapine's effectiveness in treating severe morning sickness when usual medications don't work. Participants will first try common anti-nausea drugs before moving on to Mirtazapine.

What are the potential side effects?

Mirtazapine may cause drowsiness, increased appetite leading to weight gain, dry mouth, constipation or diarrhea. It can also potentially lead to mood changes or agitation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ weekly for three weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~weekly for three weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and weekly for three weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Vomiting

Secondary study objectives

9-Item Patient Health Questionnaire (PHQ-9)

Columbia-Suicide Severity Rating Scale (C-SSRS)

Anxiety Disorders

+4 more

Side effects data

From 2014 Phase 4 trial • 38 Patients • NCT01178671

44%

nausea

43%

decreased libido (men)

43%

sexual dysfunction (men)

33%

fatigue

28%

sweating

28%

constipation

28%

somnolence

28%

decreased appetite

28%

dry mouth

28%

urinary dysfunction

28%

diarrhea

28%

tremor

27%

decreased libido (women)

22%

forgetfulness

22%

lightheadedness

22%

impaired concentration

18%

sexual dysfunction (women)

17%

heartburn

17%

apathy

17%

emesis

17%

headache

11%

insomnia

11%

increased appetite

11%

incoordination

11%

blurry vision

restlessness

nervousness

skin problems

bruising

100%

80%

60%

40%

20%

Study treatment Arm

Sertraline and Sugar Pill

Sertraline and Mirtazapine

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Mirtazapine Treatment ArmExperimental Treatment1 Intervention

Subjects will be administered the initial dose of mirtazapine, with dosage progressively increased over the course of the study. The initial dose of mirtazapine is 15 mg tablet, once per day. The dose will be increased weekly as tolerated up to 45 mg per day. The dose will be increased by 15 mg each week if the lower dose is tolerated without significant side effects. That is to say, the subject will take 15 mg/day every day for the first week, 30 mg/day every day for the second week, and 45 mg/day every day for the third week, with the option of the subject continuing the medication for the remainder of the pregnancy. If subjects choose to discontinue the mirtazapine, there will be a tapering regimen: if a patient is taking 45 mg at the end of week 3, they will begin a taper (by week) of 30 to 15 to 7.5 to 0 mg. If they relapse or has discontinuation symptoms, the previous effective dose will be given. They may attempt to taper again with the same approach.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Mirtazapine

FDA approved

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for morning sickness work through various mechanisms to alleviate symptoms. Mirtazapine, for example, increases norepinephrine and serotonin release by antagonizing central presynaptic alpha-2 adrenergic receptors, which can help reduce nausea and stabilize mood. Antihistamines like doxylamine block histamine receptors to mitigate nausea, while vitamin B6 (pyridoxine) aids in neurotransmitter synthesis and function. Understanding these mechanisms helps in choosing the most effective treatment tailored to the patient's needs.

Investigation of the role of the serotonergic activity of certain subtype-selective alpha1A antagonists in the relaxant effect on the pregnant rat uterus in vitro.Increased 5-HT contractile response in late pregnant rat myometrium is associated with a higher density of 5-HT2A receptors.Characterization of serotonin receptors in pregnant human myometrium.