Aprepitant (brand name Emend) is a drug used to prevent stomachaches and vomiting in persons receiving cancer-killing medicines (chemotherapy) or who have received medicines to prevent pain during surgery (anesthesia). The drug also affects substances in the part of the brain also associated with emotions, which has led scientists to question whether aprepitant could be used to treat certain mental disorders, particularly major depression.
Aprepitant is classified as a substance P neurokin-1 (NK-1) receptor antagonist. This means it blocks proteins called NK-1 receptors, which sit on cells in the brain region linked to gastrointestinal problems and the body’s response to stress, anxiety, and depression. The receptors attach or bind to a naturally occurring chemical called substance P, which is found in higher amounts in persons with depression. Blocking the NK-1 receptors causes a decrease in the normal action of substance P that would be mediated by the NK-1 receptor
Scientists have theorized that aprepitant could possibly become a unique antidepressant. In 1998, researchers reported that more than half of patients with depression who took aprepitant had an improvement in mood. The study involved 213 people who took the drug for six weeks. The scientists also discovered that the medicine worked as well as paroxetine (Paxil) in reducing anxiety.
In 2001, however, a larger trial involving 700 patients with mild to moderate depression failed to show that aprepitant worked any better than existing antidepressant medications. Additional studies also failed. In 2003, Merck & Company, the manufacturer of aprepitant, said it would no longer pursue the drug as a treatment for depression. The decision came just a few months after aprepitant received United States Food and Drug Administration (FDA) approval as a preventive for chemotherapy-related stomach upset.
Some researchers still investigate aprepitant as a possible treatment for depression, but the results continue to be disappointing. In 2006, research concluded that aprepitant did not reduce depression symptoms any better than the placebo.
Aprepitant is only approved to prevent nausea and vomiting in persons receiving chemotherapy or who have just had surgery. It comes in capsule form, and is taken by mouth with or without food.
Chemotherapy-related nausea and vomiting
Those receiving chemotherapy take aprepitant for three days, in combination with other drugs. The general recommended dose is as follows:
- Day 1: 125 mg by mouth one hour before receiving chemotherapy
- Day 2: 80 mg by mouth in the morning
- Day 3: 80 mg by mouth in the morning
Post-operative nausea and vomiting
Aprepitant is given alone to prevent upset stomach and vomiting that can occur after surgery. The recommended dosage is 40 mg, taken by mouth, within three hours before receiving anesthesia.
Aprepitant is well tolerated in those with mild to moderate liver disease. No aprepitant studies have been conducted in persons with severe liver disease. The drug has not been tested in people under age 18.
The FDA classifies a drug according to how it may affect a developing fetus. Aprepitant is in category B. Animal studies have shown that the drug does not harm a developing fetus, but the drug has not been studied in pregnant women. It is unclear whether the drug passes into breast milk. Women who are pregnant or breastfeeding should talk to their doctor before taking this drug.
Studies of more than 3,000 people show that aprepitant is generally well tolerated. The most common side effects in persons taking 80-125 mg aprepitant to prevent chemotherapy-related nausea and vomiting are:
- extreme tiredness
- hair loss
- loss of appetite
- stomachaches and pains
The most common side effects in persons taking 40 mg aprepitant to prevent nausea and vomiting after an operation are:
- low blood pressure
The following symptoms are rare, but require immediate medical attention:
- breathing difficulty
- hoarseness (rough, scratchy voice)
- skin rash
- swelling of the face, throat, tongue, lips, hands, or lower legs and feet
- trouble swallowing
Anesthesia —Medicines that block pain signals from traveling along the nerves to the brain. Anesthesia is often given before surgery so the patient does not feel any pain during the procedure.
Chemotherapy —The use of medicines to kill cancer cells.
Receptor —A molecule, such as a protein, on a cell’s surface that attaches to a specific substance.
Aprepitant has been linked to tumor development in laboratory animals. It is unclear if the medicine increases the risk of tumors in humans.
Serious, life-threatening reactions can occur if aprepitant is taken with any of the following drugs:
- astemizole (Hismanal)
- cisapride (Propulsid)
- pimozide (Orap)
- terfenadine (Seldane)
Aprepitant can increase levels of certain chemotherapy drugs in the blood. Patients who take aprepitant with any of the following drugs should be very carefully monitored by a doctor:
- docetaxel (Taxotere)
- etoposide (Etopophos, Vepesid)
- ifosfamide (Mitoxana)
- imatinib (Gleevec)
- irinotecan (Campto)
- paclitaxel (Taxol)
- vinblastine (Velbe)
- vincristine (Oncovin)
- vinorelbine (Navelbine)
Those who take aprepitant with the blood thinner warfarin should be closely monitored by a doctor. Taking the two drugs together can affect blood-clotting time. Blood tests are needed to determine whether the dosage of warfarin needs to be adjusted.
Aprepitant can cause increased levels of dexamethasone (Decadron) and methylprednisolone (Medrol) in the blood. Patients may need their dosages decreased if taken with aprepitant.
Aprepitant should be used with caution when taking the following drugs, which can increase the risk of side effects:
- alprazolam (Xanax)
- midazolam (Versed)
- triazolam (Halcion)
Karch, Amy M. 2007 Lippincott’s Nursing Drug Guide. Philadelphia: Lippincott Williams & Wilkins, 2007.
Mental Health America. 2000 N. Beauregard Street, 6th Floor. Alexandria, VA 22311. Telephone: (800) 969-6MHA (6642). <http://www.nmha.org>.
National Alliance on Mental Illness. 2107 Wilson Boulevard, Suite 300, Arlington, VA 22201-3042. Telephone: (703) 524-7600. <http://www.nami.org>.
National Institute of Mental Health. 6001 Executive Boulevard, Room 8184, MSC 9663, Bethesda, MD 20892-9663. Telephone: (301) 443-4513. <http://www.nimh.nih.gov>.
Kelli Miller Stacy