In the next chapter, you will see that I recommend against combination drug therapies for most patients taking antidepressants. If you take more than one drug at a time, you increase the chances for dangerous drug interactions. In addition, the second medication may create new and different side effects. In most cases, if you and your doctor work together and use a little common sense, it will not be necessary to treat antidepressant drug side effects by adding additional drugs.
How Can I Prevent Potentially Dangerous Interactions between Antidepressants and Other Drugs, Including Nonprescription Drugs?
In recent years doctors have become increasingly aware that certain types of drugs may interact with each other in ways that can be dangerous. Two drugs may be quite safe and have few or no side effects if you take either one separately; but if you take the two drugs at the same time, there could be serious consequences because of how the two drugs interact with each other.
This problem of drug interactions has become increasingly important in recent years for two reasons. First, there is an increasing trend among psychiatrists to prescribe more than one psychiatric drug at a time to many of their patients. This is not an approach with which I am entirely comfortable, but it is nevertheless very common. Each new drug raises the possibility of drug interactions, since different psychiatric drugs can interact with each other in potentially dangerous ways. And, as noted in the last chapter, more and more patients are being put on antidepressant drugs (as well as other types of psychiatric drugs) for prolonged periods of time, sometimes indefinitely. This is also not an approach with which I am comfortable, and I have found that long-term drug treatment for depression is not necessary for most patients. But many psychiatrists do prescribe drugs for prolonged times—the practice is in vogue. And if you do take a psychiatric drug for a long time, eventually you will probably receive one or more prescriptions from other doctors for other medical problems. For example, your doctor might prescribe a medication for an allergy, high blood pressure, pain, or an infection. In addition, you might take an over-the-counter medication for a cold, a cough, a headache, or an upset stomach. Now the possibility of drug interactions has to be considered, because these drugs may interact with the psychiatric drug you have been taking.
Of course, it goes without saying that psychiatric drugs can also interact with tobacco and alcohol as well as street drugs such as cocaine or amphetamines. In some cases these interactions can also be quite dangerous and even fatal. Some antidepressants interact in extremely dangerous ways with commonly used drugs, including over-the-counter medications. I am not trying to be overly alarmist here. With a little education and good teamwork with your physician, you can take an antidepressant safely.
In this section I will explain why and how drug interactions happen. In addition, in Chapter 20, I will describe a number of important drug interactions for each drug or category of drug you might be taking. Remember that knowledge about these drug interactions is rapidly evolving. New information comes out almost on a daily basis. Make certain each doctor you see has a complete and accurate list of every drug you are taking, including any over-the-counter (nonprescription) drugs you take. Ask your doctor if there are any drug interactions that could be important. Ask your pharmacist the same thing. If they are not sure, ask them to check it out for you. It is virtually impossible to keep all potential drug interactions in your mind, because so much new information is constantly emerging. References and computer programs that list dangerous drug interactions are readily available to help with this task. If you are appropriately assertive and have a little education about the topic, you will be in a better position to have an intelligent discussion with your doctor about interactions among the drugs you are taking.
You will see in Chapter 20 that I have prepared detailed charts listing drug interactions for specific antidepressants or mood stabilizers you may be taking. So, for example, if you are taking Prozac, you can review the table that lists its drug interactions. This should take only a minute or two.
You may think that you shouldn’t have to study these charts, because your doctor should know all about any dangerous drug interactions and ensure that nothing bad happens to you. There are several problems with this line of reasoning. First, though your doctor may be extremely knowledgeable, she or he is also human and cannot keep up with all the new information that is emerging, no matter how smart she or he may be. Second, even if your doctor told you about every conceivable drug interaction, there is no way you could remember all of them! And third, in this era of managed care, doctors are having to manage more and more patients, and you may get only a few minutes with your prescribing physician at infrequent intervals to review your symptoms and the dose of the medication. There may simply not be enough time to discuss all the possible drug interactions you need to know about.
How and Why Do These Drug Interactions Occur?
There are four basic ways that two drugs can interact. First, one drug can cause the level of a second drug in your blood to increase—sometimes to an alarming degree, even though you are taking only a “normal” dose of both drugs. What are the consequences of a sudden increase in the level of a drug in your blood? First, you may experience more side effects, since they are usually related to the dose. Second, many psychiatric drugs lose their effectiveness when the dose is too high or too low. And third, there can be toxic and even fatal reactions when the blood level of any drug becomes too high.
A second type of drug interaction is just the opposite. One drug can cause the level of another drug in your blood to decrease. This can cause the second drug to become ineffective, even though you are taking a normal dose. You and your doctor may wrongly conclude that the drug does not work for you when the real problem is that your blood level is too low.
A third type of interaction is when two drugs each have similar effects or side effects that intensify each other. Suppose, for example, that you are being treated for high blood pressure and then you begin to take a psychiatric drug that also lowers blood pressure as a side effect. The result could be that you might experience a sudden drop in blood pressure and possibly even faint when you suddenly stand up.
A fourth and more ominous type of drug interaction is not related to changes in blood levels but simply to toxic effects of certain drug combinations. In other words, two drugs that are safe when taken separately may lead to extremely dangerous interactions when you take them together.
Now let’s examine the first two types of drug interactions in more detail. Why does one drug sometimes cause the level of a second drug to increase or fall dramatically? Well, a simple way to think about it would be to imagine that you are trying to fill a bathtub with water. If the plug is out, the water will have a tendency to go out as fast as it comes in. As a result, the water level in the tub will not go up high enough to take a bath, no matter how long you leave the faucet on. In contrast, if the plug is in the tub and you don’t turn the water off, the tub will overflow.
Now compare your body to the bathtub. (I do not mean to imply that you have a bad figure!) The medicine you take each day is like the water coming into the tub. Certain enzyme systems in your liver can be compared to the hole in the bottom of the tub. These enzymes in your liver chemically change drugs into other substances (called “metabolites”) that your kidneys can get rid of more easily. This process is called “metabolism.” Metabolites of the drugs you take usually end up in your urine.
When you add a second drug, your liver may metabolize the first drug more slowly. This would be comparable to plugging up the hole at the bottom of the tub. And so, as you keep taking the first medicine, your blood level gets too high, in just the same way that the water in the tub gets too high and eventually spills over the side. Or the second drug you take could have the opposite effect of making the hole in the bottom of the tub much bigger. In this case, your liver’s metabolism speeds up and rids your body of the first drug much faster. In this case, you may keep taking the same dose
of the first drug each day but your blood level remains too low to have the desired antidepressant effect. In this case, the water goes out of the tub just as fast as it comes in.
That’s pretty much the basic principle. The drugs that are likely to interact with each other are those that are metabolized by the “cytochrome P450” enzyme systems in the liver. There are many of these enzyme systems, and different kinds of drugs are metabolized by different enzyme systems. Only certain drugs or combinations of drugs will stimulate or inhibit any of these enzyme systems. Psychiatric drugs can interact with other psychiatric and nonpsychiatric drugs, such as antibiotics, antihistamines, or painkillers. In other words, psychiatric drugs can affect other drugs your doctor may prescribe (such as a pill for high blood pressure), in exactly the same way that those other drugs can have an impact on any psychiatric drugs you may be taking. The bottom line is that the level of any drug you are taking might become too high or too low if you are also taking another drug at the same time.
Let me now give you some specific examples of these drug interactions. Suppose you are taking one of the new selective serotonin reuptake inhibitors called paroxetine (trade name Paxil). This drug is very similar to Prozac. Now suppose that the paroxetine is not working very well, which sometimes happens, and you are still feeling depressed. Your doctor might decide to add a second antidepressant. If your doctor chooses desipramine (trade name Norpramin), the paroxetine you are taking will have the effect of “plugging up the tub.” Now your body will not be able to metabolize the new drug (desipramine) very well. As a result, your blood level of desipramine may increase to three to four times higher than expected. Most psychiatrists are aware of this drug interaction and will be careful to prescribe desipramine in a tiny dose if a patient is taking an SSRI like paroxetine. But if your psychiatrist was not aware of this particular drug interaction and decided to give you a “normal” dose of desipramine, you could develop a toxic level of desipramine in your blood.
Is this serious? Well, there are three potential problems. First, desipramine is not effective at excessively high blood levels. Second, there will be many more side effects at high levels. And third, in rare instances, excessive blood levels of desipramine can trigger abnormal heart rhythms and occasionally even cause death.
Is this type of drug interaction rare? No. The levels of antidepressants can sometimes increase or decrease quite dramatically when combined with common prescription or over-the-counter drugs you might take without thinking twice. The tables in Chapter 20 will delineate the interactions most important to any antidepressant you might be taking.
Finally, some toxic and dangerous drug interactions do not necessarily depend on doses or blood levels. For example, many of the newer antidepressants such as Prozac have powerful effects on the serotonin systems in the brain. The monoamine oxidase inhibitors (MAOIs) also affect the serotonin systems in the brain, but through a different mechanism. The antidepressant tranylcypromine (trade name Parnate) is an example of one of these MAOI drugs. If you take Prozac and Parnate at the same time, the combination could trigger an extremely dangerous reaction known as the “serotonin syndrome.” The symptoms can include fever, muscle rigidity, and rapid changes in blood pressure, along with agitation, delirium, seizures, coma, and death. Obviously, this combination of drugs should not be given!
You will see in Chapter 20 that many medications can be dangerous if you are taking an MAOI. The list of forbidden drugs includes many antidepressants, some decongestants (especially if they contain dextromethorphan, a common ingredient of cold preparations), antihistamines, local anesthetics, some anticonvulsants, some painkillers such as meperidine (Demerol), antispasmodics including cyclobenzaprine (Flexeril) and weight-loss preparations. Some of these drugs will cause the serotonin syndrome described above, and some of them will cause another dangerous reaction known as a “hypertensive crisis.” In extreme cases, the symptoms of a hypertensive crisis include brain hemorrhage, paralysis, coma, and death. Certain common foods such as cheese are also on the “forbidden” list if you are taking one of the MAOIs, because they can cause a hypertensive crisis as well.
Many doctors do not prescribe the MAOIs because of concerns about these toxic interactions. You may also think: “Well, I will just take a safer drug so I won’t have to worry.” This makes good sense, since many safer medications are available. However, many commonly prescribed antidepressants can cause dangerous interactions. For example, two common antidepressants, nefazodone (trade name Serzone) and fluvoxamine (trade name Luvox) should not be combined with several commonly prescribed drugs because these particular combinations can trigger an abnormal heart rhythm that may result in sudden death. The drugs include terfenadine (trade name Seldane and used for allergies), astemizole (trade name Hismanal and used for allergies), or cisapride (trade name Propulsid, a stimulant for the gastrointestinal tract).
I do not mean to give the impression that it is dangerous to take antidepressant drugs. To the contrary, they are usually quite safe and effective, and the catastrophic drug interactions I have described are fortunately rare. In addition, most psychiatrists go to great lengths to educate themselves about recent developments and try to keep up with new information about side effects and drug interactions. But in the real world we live in, no doctor is perfect and no doctor can have comprehensive knowledge about all possible drug interactions. For example, your primary care physician may not be familiar with some new antidepressant your psychiatrist has prescribed. And so a little research on your part will be helpful. As an enlightened consumer, you can read about any antidepressant medicine you are taking in Chapter 20 and in other readily available references such as the Physician’s Desk Reference (PDR). You can find these books at any library, bookstore, or pharmacy. You can also find the PDR at your doctor’s office. You can also review the drug insert that comes with the medication. It doesn’t take more than five or ten minutes to review this information. Then you can ask informed questions and bring out the best in your physician. The teamwork can give you a safer and better experience with your antidepressant. This is definitely one case where an ounce of prevention can be worth more than a pound of cure.
Chapter 20
The Complete Consumer’s Guide to Antidepressant Drug Therapy*
(Notes and References appear on pages 682–687.)
In this chapter I will give you practical information about the costs, doses, side effects, and drug interactions for all the currently available antidepressant and mood-stabilizing drugs. I would recommend you use this chapter as a reference source rather than trying to read it all at once—there is just too much detailed information to digest at one sitting. If you want to learn about a particular drug that you or a family member may be taking, the Table of Antidepressants on pages 514–515 will help you locate the information you need in this chapter. Let’s assume, for example, that you are taking fluoxetine (Prozac). You can read the section on the SSRI antidepressants starting on page 547. In addition, the section on drug costs starting on this page, as well as the information starting on page 659, should be of general interest to all readers.
Table of Antidepressants
Antidepressant Drug Class
Chemical Name (and Trade Name)a
Page #
Tricyclic Antidepressants
524
amitriptyline (Elavil, Endep)
clomipramine (Anafranil)
desipramine (Norpramin, Pertofrane)
doxepin (Adapin, Sinequan)
imipramine (Tofranil)
nortriptyline (Aventyl)
protriptyline (Vivactil)
trimipramine (Surmontil)
Tetracyclic Antidepressants
524
amoxapine (Asendin)
maprotiline (Ludiomil)
SSRI Antidepressants
547
citalopram (Celexa)
fluoxetine (Prozac)
fluvoxamine (Luvox)
paroxetine (Paxil)
> sertraline (Zoloft)
MAO Inhibitors
564
isocarboxazid (Marplan)
phenelzine (Nardil)
selegiline (Eldepryl)
tranylcypromine (Parnate)
Serotonin Antagonists
599
nefazodone (Serzone)
trazodone (Desyrel)
Other Antidepressants
605
bupropion (Wellbutrin)
605
venlafaxine (Effexor)
611
mirtazapine (Remeron)
615
Mood Stabilizers
617
carbamazepine (Tegretol)
Feeling Good: The New Mood Therapy Page 44