Feeling Good: The New Mood Therapy
Page 50
Hypertensive and Hyperpyretic Crises. In rare cases, the MAOIs can produce two types of serious toxic reactions if they are not used properly. This is why so many doctors avoid using them. With good education and preventive medications, the MAOIs can be administered safely, but you will need to study this section quite carefully if you are taking an MAOI.
One of the dangerous reactions is called a “hypertensive crisis.” “Hyper” means high and “tensive” refers to blood pressure, so a hypertensive crisis is a sudden increase in your blood pressure. Increases in blood pressure are not usually dangerous and can occur in many normal situations even if you are not taking medications. For example, when you are lifting weights, your blood pressure can easily go into the range of 180/100 or higher at the moment you are straining and exerting maximum effort to raise the barbell. Our bodies are used to these temporary elevations in blood pressure. However, if you were on an MAOI and you ate one of the forbidden foods, your blood pressure might increase to dangerous levels and remain elevated for an hour or more. If you continued to eat the forbidden foods that interact with the MAOIs, sooner or later a vessel in your brain could rupture because of the mechanical stress. This would cause a stroke, certainly an excessive price to pay for taking an antidepressant.
The initial symptoms of a ruptured or leaking vessel in your brain can include an excruciating headache, a stiff neck, nausea, vomiting, and sweating. As the bleeding continues, paralysis, coma, and death can occur. Because of the danger of hypertensive reactions, your doctor will check your blood pressure at each session. The risk of a stroke is higher in individuals over sixty because our arteries become less resilient with age and are more likely to tear or rupture when subjected to the stress of a sudden increase in blood pressure. Regardless of your age, you will need to monitor your blood pressure and watch your diet carefully when taking an MAOI.
These hypertensive crises are sometimes also called “noradrenergic crises” because they are thought to be due to an excessive release of norepinephrine. Norepinephrine is a transmitter substance used by nerves in your brain and in your body. Hypertensive crises usually occur if you eat certain forbidden foods containing a substance called tyramine or if you take one of the forbidden drugs that I will describe in detail below. If you are careful, the risk of a serious hypertensive crisis is very small.
The other dangerous reaction to an MAOI is called a “hyperpyretic crisis.” “Pyretic” refers to fire, or fever. The patient with a hyperpyretic crisis may develop a high fever along with a number of alarming symptoms that can include sensitivity to light, rapid changes in blood pressure, rapid breathing, sweating, nausea, vomiting, rigid muscles, jerking and twitching, confusion, agitation, delirium, seizures, shock, coma, and death. A hyperpyretic crisis is sometimes also called a “serotonin syndrome” because it is due to an abnormal and dangerous increase in levels of serotonin in the brain. A hyperpyretic crisis occurs when the patient takes certain forbidden medications that must not be combined with the MAOIs. These drugs cause an increase in levels of serotonin in the brain. Obviously, a hyperpyretic crisis requires immediate discontinuation of the MAOI along with emergency medical treatment. The treatment may include intravenous fluids and treatment with the serotonin antagonist, cyproheptadine (Periactin), at a dose of 4 mg to 12 mg.
Several decades ago when MAOIs were first available, doctors were not as aware of the blood pressure elevations that resulted from eating foods containing tyramine or from taking the kinds of drugs described below, and so these hypertensive reactions were more common and severe. Now doctors and patients are much more aware of the problem and the risk is much smaller. In fact, extreme hypertensive and hyperpyretic reactions are quite rare. I am personally aware of only one patient, treated by a colleague in Boston, who developed a stroke due to a hypertensive crisis (noradrenergic syndrome) while taking an MAOI. I have had about half a dozen patients over the years who paged me because they suddenly developed elevated blood pressure. I told each of them to go to a local hospital emergency room for observation. In every case, the blood pressure quickly subsided without any treatment aside from observation. None of these patients experienced any adverse effects. I have never seen a patient who developed a hyperpyretic crisis (serotonin syndrome) while on an MAOI.
This is because we know a great deal about what causes these two kinds of reactions and how they can be avoided. If you are taking an MAOI, you will need to educate yourself by studying the following sections carefully. You will have to avoid taking certain types of drugs and exercise a little self-discipline in your diet in order to be safe. You will find it is well worth the extra effort required to protect yourself.
How to Avoid a Hypertensive or Hyperpyretic Crisis. There are two important keys to preventing a hypertensive or hyperpyretic crisis if you are taking an MAOI. First, you must obtain a blood-pressure cuff and monitor your own blood pressure carefully. Second, you must carefully avoid certain foods or medications (including some street drugs) that will predictably trigger these reactions. I will describe these forbidden foods and medicines in detail below. You will see that the substances that can trigger a hypertensive crisis are somewhat different from the substances that can trigger a hyperpyretic crisis.
You can obtain a blood-pressure cuff at your local pharmacy so you can monitor your own blood pressure whenever you want. Practice using the cuff. Although it may seem a little awkward or confusing at first, you will find that it gets pretty easy to take your blood pressure after you have practiced a few times. In my practice I have required every patient taking an MAOI to do this. In the rare situation where a patient did not want to go to the trouble of obtaining a cuff and learning how to use it, I have refused to prescribe an MAOI.
Initially you can monitor your blood pressure once a day or even twice a day if you are so inclined. After you have been taking the MAOI for a couple weeks, you will not need to monitor your blood pressure so frequently. Once a week will usually be sufficient. You can check your blood pressure if you forget and eat one of the forbidden foods. You can also check it if you feel woozy or nauseous or if you get an excruciating or severe headache. We all get headaches from time to time, and they rarely ever indicate a stroke. However, if you have a blood-pressure cuff, you can check your blood pressure and make sure it is not dangerously elevated.
If your blood pressure goes up to a dangerous level, you should call your doctor or go to an emergency room. How much elevation is dangerous? The blood pressure consists of two numbers. The higher number is called the “systolic” blood pressure and the lower number is called the “diastolic” blood pressure. A value of 120/80, for example, would be considered normal for most people. Most emergency room doctors would not be particularly concerned until these numbers reach the range of 190 to 200 over 105 to 110. At that level, they might observe you carefully and monitor your blood pressure every few minutes. Most of the time, the elevated blood pressure will subside without treatment. If your blood pressure continues to rise, the ER doctor could give you an antidote (such as phentolamine or prazosin) to lower your blood pressure back into a safe range.
The best time to take your blood pressure is about one to one and a half hours after you have taken the medication. About 25 percent of my patients have noted modest blood pressure elevations at this time even if they have not eaten any of the forbidden foods in Table 20–8 on pages 580–581 or taken the medicines in Table 20–9 on pages 584–590. These increases were not usually extreme or dangerous—a 20- or 30-point elevation in the systolic blood pressure was typical. Nevertheless, in those cases, I have recommended stopping the medication because these patients seemed overly sensitive to the effects of the MAOI on their blood pressure. It just did not seem worth the worry and risk, especially since a different antidepressant might be just as effective.
Foods to Avoid. Hypertensive crises may occur if you eat foods (see Table 20–8) that contain a substance known as tyramine. If you are taking an MAOI, too much tyramine can
interfere with your brain’s ability to regulate your blood pressure. Tyramine causes nerves to release more norepinephrine into the synaptic regions that separate them from the postsynaptic nerves. These postsynaptic nerves may become overly stimulated when too much norepinephrine is released. Because these nerves help to regulate blood pressure, all the extra norepinephrine that is released can cause a dangerous and sudden increase in blood pressure.
You will recall from Chapter 17 that an enzyme called monoamine oxidase (MAO) is located inside the presynaptic nerves. This enzyme usually destroys any excess norepinephrine that builds up inside these nerves and prevents these nerves from releasing too much norepinephrine when they fire. But the MAOI drugs block this enzyme, and so the norepinephrine levels inside these nerves increase substantially. When you eat foods containing tyramine, all that extra norepinephrine suddenly spills into the synaptic region, causing a massive stimulation of the nerves that regulate your blood pressure.
Table 20–8. Foods and Beverages to Avoid If You Are Taking a Monoamine Oxidase Inhibitor (MAOI)a
Foods to Avoid Completely
Cheese, particularly strong or aged cheese (cottage cheese and cream cheese are allowed)
Beer and ale: particularly tap beers, beers from microbreweries and strong ales
Red wine: especially Chianti wine
Brewer’s yeast tablets or yeast extracts (breads and cooked forms of yeast are safe. The yeast extracts from health food stores are dangerous. Yeast extracts may be found in certain soups. Some powdered protein diet supplements contain yeast extracts.)
Pods of fava beans, also called Italian green beans (regular green beans are safe)
Meat or fish that is smoked, dried, fermented, unrefrigerated, or spoiled, including:
• fermented or air-dried sausages, such as salami and mortadella (some experts state that bologna, pepperoni, summer sausage, corned beef, and liverwurst are safe)17
• pickled or salted herring
• liver (beef or chicken), especially old chicken liver (fresh chicken liver is safe)
Overripe bananas or avocados (most fruits are completely safe)
Sauerkraut
Some soups, including those made from beef bouillon or Asian soup stocks (e.g., miso soup). (Tinned and packet soups are felt to be safe, unless made from bouillon or meat extracts)
Foods or Beverages that May Cause Problems in Large Amounts
White wine or clear alcohol, such as vodka or gin
Sour cream
Yogurt: must be pasteurized and less than 5 days old to be safe
Soy sauce
NutraSweet (the artificial sweetener)
Chocolate
Caffeine in beverages (coffee, tea, and soda) and chocolate
Foods or Beverages Once Thought to Cause Problems which Are Probably Safe in Small Amounts
Figs (avoid overripe figs)
Meat tenderizers
Caviar, snails, tinned fish, pate
Raisins
aModified from B. McCabe and M. T. Tsuang, “Dietary Considerations in MAO Inhibitor Regimens,” Journal of Clinical Psychiatry 43 (1982): 178–181.
If you watch your diet carefully, the likelihood is good that you will experience no adverse blood-pressure elevation. The most common trigger is cheese, especially strong cheese. You will have to give up pizza and grilled cheese sandwiches for a while if you are taking an MAOI.
Most of the forbidden foods contain the breakdown products of protein—including tyramine. So, for example, freshly cooked chicken is perfectly safe, but cooked leftover chicken that has been sitting for a couple days can be dangerous because tyramine forms when the meat decomposes. One of my patients on tranylcypromine (Parnate) ate some leftover chicken that had been in the refrigerator for several days. Soon after eating it, he experienced a significant elevation in blood pressure. This was because the chicken had partially decomposed due to effects of bacteria. Fortunately, he was not harmed, but this experience served as a useful warning to be careful. The fermented or partially decomposed meats on the list in Table 20–8, such as strong sausage or smoked fish, as well as strong cheese, may contain large amounts of tyramine and can be especially dangerous. Some experts also advise against eating Chinese food while taking MAOIs. This may be due to the soy sauce, the monosodium glutamate, or other ingredients.
How much tyramine is necessary to cause a hypertensive reaction? This varies quite a bit from person to person. On average, foods containing at least 10 mg of tyramine will be sufficient to cause a hypertensive crisis if you are taking phenelzine (Nardil). As little as 5 mg of tyramine may be sufficient if you are taking tranylcypromine (Parnate). What foods contain this amount of tyramine? Well, most beers contain less than 1.5 mg of tyramine, and many contain less than 1 mg, so you would have to drink several beers to run a significant risk. However, some ales contain 3 mg of tyramine per serving, and some tap beers can also be particularly risky. For example, one serving of Kronen-bourg, Rotterdam’s Lager, Rotterdam’s Pilsner, or Upper Canadian Lager contains between 9 and 38 mg of tyramine17. So even one glass of these beers could be dangerous.
Cheeses can also vary greatly. Processed American cheese contains only about 1 mg of tyramine per serving, but Liederkranz, New York State cheddar, English Stilton, blue cheese, Swiss cheese, aged white cheese and Camembert all contain more than 10 mg per single serving.17
Suppose you eat one of the forbidden foods by accident, and then you check your blood pressure and discover that it does not go up. What does this mean? There is a lot of individual variation in the sensitivity to the effects of the forbidden foods. You may be one of those individuals who is significantly less likely to react with an elevation in blood pressure. However, you should not become complacent, because these hypertensive reactions are unpredictable. If you cheat and eat the forbidden foods from time to time, it is a lot like playing Russian roulette. You may get away with it for a while and then discover that you have experimented once too often. For example, you may eat a piece of pizza on nine separate occasions without any increase in blood pressure, and conclude that it is safe to eat pizza. But this can be very misleading, because the tenth time you eat a piece of pizza you may experience a sudden and severe increase in blood pressure. It is not known why this happens, but it does underscore the importance of consistent self-discipline if you are taking an MAOI.
Medications and Drugs to Avoid. A number of prescription drugs, nonprescription drugs, and street drugs that can cause a hypertensive or hyperpyretic crisis when combined with MAOIs are listed in Table 20–9 on pages 584–590. These reactions are especially dangerous and so you must carefully avoid these drugs. Some of the medications that interact with MAOIs do not cause such severe reactions. For example, caffeine may cause you to become more jumpy and jittery than usual. Moderate amounts of caffeine are reasonably safe, however. (You may think of caffeine as more of a food than a drug, but it is a mild stimulant.)
The list of drugs that interact with MAOIs includes:
• most antidepressants—virtually any of them can be dangerous;
• many antiasthma drugs;
• many common cold, cough allergy, sinus, decongestant, and hay fever medications that contain sympathomimetic agents (discussed in detail below) or dextromethorphan, the cough suppressant. You will have to check labels carefully, because many over-the-counter drugs contain these substances;
• drugs used in the treatment of diabetes—they may become more potent than usual if you are taking an MAOI, and can cause your blood sugar to fall more than expected;
• some drugs used in the treatment of low or high blood pressure—both types of drugs can in some cases cause blood pressure elevations when combined with MAOIs;
• mood stabilizers and anticonvulsants;
• some painkillers, including some local and general anesthetics;
• sedatives (including alcohol) and tranquilizers—they may have more pronounced effects than usual when you are taking
an MAOI. The increased sleepiness could be hazardous if you are driving;
• L-tryptophan—the natural amino acid;
• stimulants (pep pills) and street drugs;
• many weight-loss (appetite suppressing) medications;
• caffeine, which is present in coffee, tea, many sodas, hot cocoa, and chocolate. Caffeine is also present in a number of prescription and nonprescription medications such as Cafergot suppositories and tablets, Darvon Compound-65, NōDōz, Fiorinal, Excedrin, and many other cold or pain preparations;
• Disulfiram (Antabuse), used to treat alcoholism;
• Levo-dopa, used in the treatment of Parkinson’s disease.
Table 20–9. Prescription Drugs and Over-the-Counter Medications to Avoid If You Are Taking a Monoamine Oxidase Inhibitor (MAOI)a
Note: This list is not exhaustive; new information about drug interactions comes out frequently. If you are taking an MAOI and any other medication, ask your doctor and pharmacist if there are any drug interactions.
Antidepressants
Drug
Comment
tricyclic antidepressants,b especially desipramine (Norpramin, Pertofrane) and clomipramine (Anafranil)
Some (e.g., clomipramine) may cause a hyperpyretic crisis or seizures; others (e.g. desipramine) may cause a hypertensive crisis
tetracyclic antidepressants, especially bupropion (Wellbutrin)
hypertensive crisis (noradrenergic syndrome)
SSRIs (all are extremely dangerous)
hyperpyretic crisis (serotonin syndrome)
other MAOIs
hyperpyretic crisis (serotonin syndrome); hypertensive crisis (nonadrenergic syndrome)