moderate
50-150 mg
pattern 1
r-■
A1=44)
c.,4
least
moderate
10-60 mg
pattern 2
••.1
Protriptyline (
vs
VIvactil)
Dompta
least
150-300 mg
pattern 1
8
substantial
(Sinequan, AdaPin)
CThe clumilleel same is given that, and the brand names are indicated in parentheses. If your doctor uses the chemical name on the pro-the drone* can substitute • cheaper brand if you request It and If one fa mailable.
•▪ ReceeS SNOW sunset that those dram which are meetly sedative may here the greatest effect in combating armlet, and nervousness. Who gives at eight, the sedative agent, bells reduce insomnia.
ensile Me fads, if troublesome, can be minimised by a reduction in doeage. Side effects are greatest the first few days and tend to dfravpeat
•The dam emild be geed for the treatment of en episode of depression. Some patients may require and benefit from doses outside the await range. If maintenance therapy following recovery fa felt to be appropriate, two thirds of the dose taken during the acute phase of imam= arm be med.
• hem It Up to beff the mesimunt indicated dose may be taken on • enetsper.day basis at night before bedtime. This dosage pre-load deep, and atom dde effects will occur when you are asleep. If larger doses are required, the additional medicine can be given at madames in divided amounts.
Pattern 2t This medicine fa effmulating and should be taken in divided doses in the morning and at noon. If taken later in the day, the medication may interfere with Sleep.
David D. Burns, M.D.
the wiring in the brain develops faulty connections. The result will be mental and emotional static, much like the music that comes out of a radio with a loose wire in the tuner. The emotional static would correspond to depression.
Conversely, manic states—in which the patient is overwhelmed by an uncontrollable, emotional high—are thought to be due to an excessive level of activity of these chemical messengers, leading to hyperactive nerve function.
How do antidepressant drugs correct this? There are four categories of antidepressant agents in use. The widely prescribed "tricyclic" antidepressants (see Table 17-1, page 379) appear to enhance the potency of the brain's mood messengers in the synaptic junction, although they do not cause an actual increase in the levels of these substances.
A second category of antidepressant medications is known as the "M.A.O. Inhibitors," such as Parnate (tranylcyprom-ine), Marplan (isocarboxazid), and Nardil (phenelyzine).
These drugs lead to an actual elevation of the levels of amine messengers in the emotional regions of the brain. As the brain becomes loaded with extra amounts of chemical transmitters, the presumed chemical amine deficiency is corrected.
Lithium carbonate is the third type of antidepressant. The effects of lithium are more complex and less clearly understood. Lithium is similar to ordinary table salt, and is known as an "electrolyte." It smooths out destructive mood cycles in patients whose emotions swing back and forth unpredictably from uncontrollable and extreme elation to deep despair. It is not known for certain how one drug can have two opposite effects and this paradox is one of many challenging puzzles that psychiatric researchers are trying to solve. One current theory suggests that lithium stabilizes the chemical-messenger levels so that cyclic oscillations in amine concentrations are less apt to occur.
L-tryptophan is the fourth and newest type of antidepressant. It is a naturally occurring amino acid that is present in a normal diet, and is used by the brain in the synthesis of one of the chemical messengers. Thought to be vital to mood regulations, it has been subject to intensive research in the past decade. L-tryptophan is particularly fascinating because it passes rapidly from the stomach to the mood centers of the
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brain, and thus it has been promoted as a natural antidepressant agent.
Research in the next decade will undoubtedly advance our understanding of how the brain regulates emotional states, and, it is hoped, our armamentarium of antidepressant agents will be greatly expanded and strengthened. At present, we can only say:
1. There are at least a dozen different antidepressant drugs that do work.
2. For some patients these drugs are profoundly effective, while for others the results are disappointing.
3. We can only make educated guesses about which agent will work best for which patient. Some patients may need to try several antidepressants until the one that works best is found because we do not yet have completely effective methods for determining the correct drug based on clinical characteristics or laboratory tests.
4. Blood tests for measuring levels of tricyclic antidepressants have been recently developed in research centers and are rapidly becoming clinically available. These blood tests will guide therapists in administering the proper dose of antidepressant and may substantially improve the therapeutic effectiveness and safety of the medications.
What You and Your Doctor Need to Know
About Commonly Prescribed Antidepressants
Tricyclic Compounds. The tricyclic antidepressants are the most widely prescribed compounds at this time (the word "
tricyclic" simply refers to their chemical structure, which resembles three connected rings). A list of the most generally prescribed tricyclic compounds, along with useful information about the dose range, method of administration, and side effects, is included in Table 17-1, page 379.
The most common error your doctor is likely to make is to prescribe a dose that is too low. This statement may run against your grain if you intuitively feel you should take the lowest dose possible. In the case of tricyclics, if the dose
381
David D. Burns, M.D.
prescribed is too low, they will not be completely effective. If you insist on taking a daily dose that is too low, you will be wasting your time. It simply will not help you. On the other hand, dosages above those recommended in Table 17-1 can be dangerous, and in some cases can lead to a worsening of your depression. My advice in a nutshell: Go to a physician who specializes in treatment with antidepressant drugs; follow his advice within reason; and review Table 17-1 with him if you suspect you may be taking an inappropriately large or small dose.
Another error your doctor may make is to keep you on a particular antidepressant for many months even when there is no clear-cut evidence that you have improved. This makes absolutely no sense to me, yet I have seen many severely depressed individuals who report they have been treated continuously with the same antidepressant for months or years and were not aware of any beneficial effects! In such a case it is abundantly clear that the drug has not worked. So why keep taking it? If a drug does not begin to have fairly substantial effects, as indicated by a continuing drop in the score on the BDI test (see Chapter 2) after a three- to four-week trial at an adequate dose, then it is usually appropriate to switch to another tricyclic agent.
The best way to begin taking a tricyclic medicine is to start out with a small dose and to increase the amount each day until a dose within the normal therapeutic range is achieved.
This buildup can usually be completed within one week. For example, a typical daily dose schedule for 'imipramine, the first drug listed in Table 17-1, might be:
Day one-50 mg at bedtime;
Day two-75 mg at bedtime;
Day three-100 mg at bedtime;
Day four-125 mg at bedtime;
Day five-150 mg at bedtime.
If doses larger than 150 milligrams per day are required, the additional medicine should be given in divided doses during the daytime. Doses up to 150 milligrams per day can be conveniently taken once a day at night. The antidepressant effect will last all day long, and the most bo
thersome side effects will occur at night, when they will be least noticed.
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The most common side effects are sleepiness, dry mouth, mild hand tremor, transient lightheadedness, and constipation.
These symptoms usually occur in the first few days and, with the exception of dry mouth, tend to diminish as you become accustomed to the drug. If you simply put up with them, they will frequently disappear spontaneously after a few days. If the effects are strong enough to make you uncomfortable, it is best to reduce the dose gradually, but do not do so abruptly. Sudden discontinuation of the medicine may result in an upset stomach and insomnia.
Side effects that suggest you are taking an excessive dose include difficulty in urination, blurred vision, confusion, severe tremor, substantial dizziness, or increased sweating. A dose reduction for such symptoms is definitely indicated.
A stool softener or laxative can help if constipation develops. Lightheadedness is most likely to occur when you stand up suddenly—this is due to blood collecting in the legs and persists for a few seconds. If you get up more carefully and slowly, or if you exercise your legs before standing (by tightening and then relaxing your leg muscles as when you run in place), this should not be a problem.
Some patients describe feeling "strange," "spaced-out," or "
unreal" during the first few days of drug administration.
Similar reactions were observed in a study in which patients received sugar pills (placebos) they thought were antidepressants. This suggests that many so-called side effects may be imaginary to a certain extent and result from fears about the medication rather than from any actual effect of the drug itself. When patients report feeling strange on the first day or two of taking an antidepressant, I usually advise them to stick with it, and in nearly all cases this uncomfortable sensation disappears completely within a few days.
The tricyclic compounds may stimulate your appetite. If you have been losing weight due to depression, this appetite boost can be beneficial. However, if you are overweight you might have to pay more attention to dietary consideration in order to avoid additional weight gain, which can be demoral-izing.
How long will it take before you can expect to feel better?
It usually requires a minimum of two or three weeks before the medicine begins to improve your mood. It is not known 383
David D. Burns, M.D.
why antidepressants have this delayed reaction (and whoever discovers the reason will probably be a good candidate for a Nobel Prize). Many patients have the impulse to discontinue their antidepressants before the three weeks have passed because they believe the medicine is not working. This is illogical and self-defeating, since it is unusual for these agents to become effective right away.
How much mood elevation should you anticipate? My own philosophy is to use the BDI test as a guide (Chapter 2).
Take the test once or twice a week during your treatment.
Your aim should be to reduce the score until it is in the range considered normal (under ten). Treatment cannot be considered completely successful if your score remains over ten. If after three to four weeks of drug treatment the BDI score has not begun to fall substantially, I would advise discontinuation of that drug. In this case your doctor is likely to recommend that you switch immediately to another tricyclic antidepressant. This makes good sense because many patients who do not respond adequately to the first agent will have a positive response to the second or third. If you still have not improved after trying several different tricyclic drugs, it might be best to switch to a completely different type of antidepressant, such as the M.A.O. Inhibitors.*
What are the chances you will respond to a particular tricyclic? Most studies have reported approximately 65 percent of depressed patients will respond to the first tricyclic antidepressant they are given. Since approximately 30 percent of those treated with a sugar pill also recover, an antidepressant will double your chances for recovery during the first month or two of treatment. If you try several agents in succession, your chances for recovery are much higher. But do not take several different drugs simultaneously!
After you have responded adequately, how long should you continue to take the medicine? You and your doctor will have to make this decision together. If this is your first depressive episode, you can probably go off the medicine, and
* If you switch from a tricyclic drug to an M.A.O. Inhibitor, it is mandatory that you be drug-free for at least ten days. Similarly, if you switch from an M.A.O. Inhibitor to a tricyclic drug, a ten-day drug-free period is also mandatory. This is because dangerous interactions between M.A.O. Inhibitors and tricyclic compounds can occur.
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you will continue to feel like your normal self. If you have had many years of unremitting depression, or if you have been prone to recurrent attacks, you might want to consider maintenance therapy for a year or more at two thirds of the dose you were on when you improved. Recent research indicates that such maintenance therapy can reduce the incidence of depressive relapses. Since doctors are becoming more and more aware of the relapsing nature of mood disorders, the use of antidepressants on a prophylactic basis is gaining a greater favor.
What should you do if at some future time the depression comes back? Should you try a new drug? No! The chances are that you will again respond to the original agent. It may be the proper biological "key" for you. So use that drug again—go with a winner! If any blood relative of yours develops a depression, this same drug might also be a good choice for them because a person's response to antidepressants, like the depression itself, appears to be influenced by genetic factors.
M.A.O. Inhibitors. These agents were the first antidepressants to receive widespread use many years ago, but then they fell into relative disuse when the newer and somewhat safer tricyclic compounds were developed. In recent years the M.A.O. Inhibitors have experienced a resurgence of popularity because they are often remarkably effective for patients who do not respond to tricyclics, especially those who have experienced so many years of depression that this miserable illness has become an unwelcome life-style. The M.A.O. Inhibitors are particularly effective in an atypical depression that is characterized by phobias and high levels of anxiety, chronic anger, hypochondriacal complaints, or impulsive self-destructive behavior. Patients with recurrent obsessive thoughts and compulsive, ritualistic, nonsensical habits (such as recurrent hand-washing or repetitive checking of door locks) also often experience relief when treated with M.A.O.
Inhibitors. These drugs require careful medical management and close teamwork with your doctor. They are well worth the effort because they can be lifesaving when other drugs have proved ineffective, and can lead to profound, beneficial mood transformations.
Like the tricyclic compounds, the M.A.O. Inhibitors re-
385
David D. Burns, M.D.
quire at least two or three weeks to become effective. Your doctor will want to obtain a medical evaluation before starting you on this type of drug. This evaluation should include a physical examination, a chest X ray, an electrocardiogram, a blood count, blood chemistry tests, and a urinalysis. The most commonly prescribed drugs are Parnate, Nardil, and Marplan. The dose ranges are given in Table 17-2. A common prescribing error is to give too big a dose too soon. Because these drugs sometimes tend to be stimulating, they can cause insomnia. In order to minimize this possibility, the entire dose can be taken once a day in the morning. The stimulating effects of the M.A.O. Inhibitors can be especially helpful to depressed individuals who often feel tired, lethargic, and unmotivated. They may provide some much needed go power.
Table 17 2.
-
Dose Ranges for M.A.O. Inhibitors
Trade Name
Chemical Name
Dose Range
Marplan
Isocarboxazid
10-30 mg per day
Nardil
Phenelyzin
e
15-75 mg per day
Parnate
Tranylcypromine
10-50 mg per day
The side effects are similar to those of the tricyclic drugs but are usually very mild: dry mouth, lightheadedness when standing suddenly, a delay in starting urination, or a rash. A loosening of the stool or constipation might occur. These side effects are not dangerous.
The M.A.O. Inhibitors can in rare cases produce some serious toxic effects if they are not used properly. The most dangerous is the elevation in blood pressure that may occur if you eat certain foods or take certain drugs that are forbidden (see Table 17-3, opposite page). For this reason your blood pressure must be checked by your therapist at each session, or you might want to obtain your own blood-pressure cuff and monitor it daily just to be on the safe side. The foods you must avoid contain a substance known as "tyramine," which might interfere with your brain's ability to regulate your blood pressure properly if you are taking an M.A.O. Inhibitor. If you watch your diet carefully, you should experience no adverse blood-pressure elevation.
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Table 17-3. Foods and Medications to Avoid If You Are Taking M.A.O. Inhibitors *
FOODS: Chocolate; cheese, especially strong or aged types; pickled herring; soy sauce; pods of broad beans (fava beans); canned figs; bananas or avocados; raisins; all types of liver; yeast or yeast extract; meat prepared with tenderizer; sour cream.
BEVERAGES: Wine (especially Chianti or red wines); beer or ale; alcohol. Caffeine should be used in moderation.
MEDICATIONS•: (1) tricyclic antidepressants; (2) cold tablets, decongestants, hay fever medicines; asthma inhalers; (3) stimu-lants such as UAW or amphetamines, which are occasionally prescribed for weight loss; (4) anticonvulsants. If you are taking medicines to control high blood pressure, a consultation between your psychiatrist and internist is advisable.
DANGEROUS SIDS EFFECTS: If you develop a sudden severe headache, nausea, stiff neck, dizziness, confusion, a fear of light or other unusual symptoms, obtain an emergency medical evaluation and make certain your blood pressure is not elevated. Insomnia or an extraordinary sudden euphoria is less dangerous, but also mandates immediate intervention and may require abrupt discontinuation of the medicine.
The Feeling Good Handbook Page 42