Tranylcypromine
Tranylcypromine
Definition
Tranylcypromine is classified as a monoamine oxidase inhibitor (MAOI). It is used to treat serious depression . In the United States, tranylcypromine is sold under the brand name Parnate and under its generic name.
Purpose
Tranylcypromine is used primarily to treat depression that does not respond to other types of drug therapy. It is also used occasionally to treat panic disorder, agoraphobia , and bulimia nervosa .
Description
Tranylcypromine is a member of a class of drugs called monoamine oxidase inhibitors. Monoamine oxidase, or MAO, is an enzyme found throughout the body. In the brain , MAO breaks down norepinephrine and serotonin, two naturally occurring chemicals that are important for maintaining mental well-being and preventing depression. Monoamine oxidase inhibitors, such as tranylcypromine, reduce the activity of MAO. Less norepinephrine and serotonin are broken down, so their levels rise. This helps to lift depression.
Tranylcypromine is effective for treating depression, especially complicated types of depression that have not responded to more traditional antidepressants . However, tranylcypromine also affects the MAO enzyme in many other areas of the body. This accounts for the large number of serious side effects and drug interactions it causes.
Recommended dosage
The typical starting dosage of tranylcypromine in adults is 10 mg taken twice per day. This dosage is sometimes increased to 30 mg per day after a two-week period. The maximum recommended amount is 60 mg per day. Those over age 60 are usually started on a dose of 2.5 mg per day. After this, their doctors will make an individualized decision about increasing the dosage. Older adults typically take smaller doses and do not take more than45 mgper day. A doctor must make an individual determination of whether to give tranylcypromine to youths under the age of 18 years, because guidelines for this age group have not been developed.
The benefits of this drug may not become apparent for several weeks. Patients should be aware of this and continue taking the drug as directed, even if they do not see an immediate improvement.
Precautions
People taking tranylcypromine should not eat foods rich in tyramine. These foods include yeast or meat extracts, fermented sausage, overripe fruit, sauerkraut, cheese, and fava beans. Alcohol should not be consumed, and the same holds true for alcohol-free beer and wine. Large amounts of caffeine-containing food and beverages, such as chocolate, tea, coffee, and cola should be avoided. The treating doctor needs to approve the use of any drug, including prescription, over-the-counter drugs, and herbal treatments, that patients take while taking tranylcypromine.
Tranylcypromine should be used with great caution in pregnant and nursing women only after the risks and benefits of treatment have been assessed. Likewise, this drug may not be appropriate for people with a history of seizures , children under age 18 years, people at risk for suicide , those with severe depression, a history of schizophrenia , or diabetes mellitus. People with these conditions should discuss the risks and benefits of this drug with their physicians, and a decision to treat should be made on an individual basis. People should not stop taking tranylcypromine suddenly. Instead, the dose should be gradually reduced, then discontinued.
People with a history of high blood pressure, congestive heart failure, severe liver disease, severe kidney disease, severe heart disease, and blood vessel problems in the brain should not take tranylcypromine.
Side effects
The enzyme monoamine oxidase regulates functions throughout the body. Phenelzine decreases the activity of monoamine oxidase in all the areas of the body where it exists, not just in the brain. This is why tranylcypromine is capable of causing a wide variety of side effects in many different organ systems.
Tranylcypromine should be stopped if symptoms of unusually high blood pressure develop. These symptoms include severe chest pain, severe headache, nausea, vomiting, stiff or sore neck, enlarged pupils, and significant changes in heart rate. If these symptoms develop, it should be considered an emergency. Patients should get medical help immediately. Generally these serious side effects are rare.
More common but less serious side effects include lightheadedness or dizziness when arising from a sitting position. These symptoms need to be reported to a doctor but are not considered an emergency. Less common symptoms that should be reported include pounding heartbeat, swelling of the lower extremities, nervousness, and diarrhea. Rare but reportable symptoms include fever, skin rash, dark urine, slurred speech, yellowing of the eyes or skin, and staggering when walking. Common but not serious side effects include decreased sexual performance, increased appetite, muscle twitching, trembling, blurred vision, and reduced urine output.
Overdose symptoms include confusion, seizures, severe dizziness, hallucinations , severe headache, severe drowsiness, significant changes in blood pressure, difficulty in sleeping, breathing difficulties, and increased irritability.
Interactions
Tranylcypromine interacts with a long list of drugs. Some of these interactions can cause death. This section is not a complete list of interactions, but it includes the most serious ones. Patients must make sure every health care professional who takes care of them (for example, doctors, dentists, podiatrists, optometrists, pharmacists, nurses) knows that they take tranylcypromine, as well as all of the other prescription or nonprescription drugs and herbal remedies that they take.
The combination of tranylcypromine with any type of stimulant can increase the risk of developing serious increases in blood pressure. Tranylcypromine when taken with antidiabetic drugs can reduce blood sugar levels to far below normal. The combination of tranylcypromine with barbiturates can prolong the effects of the barbiturate drug.
KEY TERMS
Agoraphobia —People with this condition worry that they will not be able to get help or flee a place if they have a panic attack, or they may refuse to go to places that might trigger a panic attack.
Bulimia —An eating disorder characterized by binges in which large amounts of food are consumed, followed by forced vomiting.
Congestive heart failure —A condition characterized by abdominal pain, swelling in the lower extremities, and weakness caused by a reduced output of blood from the left side of the heart.
Diabetes mellitus —A chronic disease affecting the metabolism of carbohydrates that is caused by insufficient production of insulin in the body.
Panic disorder —An anxiety disorder in which individuals experience sudden, debilitating attacks of intense fear.
Schizophrenia —A severe mental illness in which people have difficulty distinguishing what is real from what is not real. It is often characterized by hallucinations, delusions, language and communication disturbances, and withdrawal from people and social activities.
Tyramine —An intermediate product between the chemicals tyrosine and epinephrine in the body and a substance normally found in many foods. It is found especially in protein-rich foods that have been aged or fermented, pickled, or bacterially contaminated, such as cheese, beer, yeast, wine, and chicken liver.
Tranylcypromine should never be combined with other antidepressant drugs, especially the selective serotonin reuptake inhibitors (SSRIs) , because of potentially severe or fatal reactions, including increased risk of dangerously high blood pressure. Patients taking tranylcypromine should stop the drug, then wait at least 14 days before starting any other antidepressant. The same holds true when discontinuing another antidepressant and starting tranylcypromine.
Alcohol combined with tranylcypromine can lead to significantly increased blood pressure. Tranylcypromine combined with the blood pressure drug guanethidine (Ismelin) can reduce the beneficial effects of the guanethi-dine. When tranylcypromine is combined with levodopa (Dopar, Larodopa), a drug used to treat Parkinson’s disease, severely increased blood pressure can develop. Tranylcypromine combined with lithium can cause fever. Meperidine (Demerol), when combined with tranylcypromine, can cause fever, seizures, increased blood pressure, and agitation. Tranylcypromine combined with norepinephrine can cause increased response to norepi-nephrine. Tranylcypromine combined with reserpine (Serpalan, Serpasil) can produce greatly increased blood pressure. When tranylcypromine is combined with the migraine drug sumatriptan (Imitrex), significantly increased concentrations of the latter drug develop that can produce potentially toxic effects.
Resources
BOOKS
Consumer Reports Complete Drug Reference.2002 ed. Denver: Micromedex Thomson Healthcare, 2001.
Ellsworth, Allan J., and others. Mosby’s Medical Drug Reference. 2001–2002. St.Louis: Mosby, 2001.
Mosby’s GenRx staff. Mosby’s GenRx. 9th ed. St. Louis: Mosby, 1999.
Preston, John D., John H. O’Neal, and Mary C. Talaga. Handbook of Clinical Psychopharmacology for Therapists. 4th ed. Oakland, CA: New Harbinger Publications, 2004.
Venes, Donald, and others, eds. Taber’s Cyclopedic Medical Dictionary. 19th ed. Philadelphia: F. A. Davis, 2001.
PERIODICALS
Adli, Mazda, et al. “Is Dose Escalation of Antidepressants a Rational Strategy After a Medium-Dose Treatment Has Failed? A Systematic Review.” European Archives of Psychiatry and Clinical Neuroscience 255.6 (Dec. 2005): 387–400.
Frieling, Helge, and Stefan Bleich. “Tranylcypromine: New Perspectives on an ‘Old’ Drug.” European Archives of Psychiatry and Clinical Neuroscience 256.5 (Aug. 2006): 268–73.
McGrath, Patrick J., et al. “Tranylcypromine Versus Ven-lafaxine Plus Mirtazapine Following Three Failed Antidepressant Medication Trials for Depression: A STAR*D Report.” American Journal of Psychiatry 163.9 (Sept. 2006): 1531–41.
Thase, Michael E. “Bipolar Depression: Issues in Diagnosis and Treatment.” Harvard Review of Psychiatry 13.5 (Sept.–Oct. 2005): 257–71.
Tulen, Joke H. M., et al. “Sustained Effects of Phenelzine and Tranylcypromine on Orthostatic Challenge in Antidepressant-Refractory Depression.” Journal of Clinical Psychopharmacology 26.5 (Oct. 2006): 542–44.
Valenstein, Marcia. “Keeping Our Eyes on STAR*D.” American Journal of Psychiatry 163.9 (Sept. 2006): 1484–86.
Mark Mitchell, MD
Ruth A. Wienclaw, PhD