Feeling Good: The New Mood Therapy (71 page)

^a
Information in this table was obtained from several sources including the
Manual of Clinical Psychopharmacology
¹
and
Psychotropic Drugs Fast Facts
.
¹⁷
These excellent references are highly recommended.

^b
This is a dangerous and potentially fatal syndrome which includes rapid changes in vital signs (fever, oscillations in blood pressure), sweating, nausea, vomiting, rigid muscles, myoclonus, agitation, delirium, seizures, and coma.

A number of other important interactions which are listed in the table involve common drugs that many people might take for a cold or flu, diabetes, high blood pressure, allergies, and so on. For example, dextromethorphan is a cough suppressant in many over-the-counter cold preparations. When combined with an SSRI, dextromethorphan can cause visual hallucinations. This has been reported with fluoxetine (Prozac) but could theoretically occur with any SSRI. You will also see that two common antihistamines, terfenadine (Seldane) and astemizole (Hismanal), can produce abnormal and potentially fatal heart rhythm abnormalities when combined with certain SSRIs, and a third antihistamine called cyproheptadine (Periactin) can block the antidepressant effects of an SSRI.

Make sure you review this table if you are taking an SSRI. If you have any questions, discuss them with your doctor and pharmacist. The SSRIs are safe for the overwhelming majority of individuals who take them. With a little good teamwork between you and your doctor, your experience with an SSRI can be positive.

The Table of Antidepressants on pages 514–515 lists four drugs known as monoamine oxidase inhibitors (MAOIs). They include isocarboxazid (Marplan), phenelzine (Nardil),
selegiline (Eldepryl), and tranylcypromine (Parnate). You may recall from Chapter 17 that the MAOIs fell into relative disuse when the newer and safer compounds were developed. They are probably vastly underutilized because they can be quite dangerous if mixed with a number of common foods (such as cheese) and medicines (including many common over-the-counter cold, cough, and hay fever drugs) and because they require fairly sophisticated medical skills on the part of the prescribing doctor.

In recent years the MAOIs have experienced a much-deserved resurgence of popularity because they are often remarkably effective for patients who do not respond to other kinds of antidepressants. Many of these patients have experienced so many years of chronic depression that their illness has become an unwelcome lifestyle. The beneficial effects of the MAOIs can sometimes be quite impressive.

The MAOIs can also be particularly effective in an “atypical depression” that is characterized by the following types of symptoms:

Patients with this form of depression sometimes also emphasize chronic feelings of fatigue as well as a “leaden paralysis.” It is not clear whether this really represents a subtype of depression or simply a particular group of symptoms that any depressed individual might experience.

Nevertheless, studies conducted at Columbia University suggest that the MAOIs may actually be better than the cyclic antidepressants for patients with these kinds of symptoms. The MAOIs can also be remarkably effective when high levels of anxiety accompany the depression, including phobias (such as social phobia), panic attacks, or hypochondriacal
complaints. Patients with recurrent obsessive thoughts and compulsive, ritualistic, nonsensical habits (such as recurrent hand-washing or repetitive checking of door locks) may also experience relief when treated with MAOIs.

The MAOIs can also be helpful when chronic anger or impulsive self-destructive behavior accompanies the depression. Patients with these features are sometimes diagnosed as having “borderline personality disorder.” Although these individuals can sometimes be quite difficult to treat, I have seen many who were dramatically helped by the MAOIs. Of course, all patients who take MAOIs must agree to follow the dietary restrictions and medication guidelines religiously. If a patient is unreliable or will not agree to this, other types of medications should be used instead.

The mechanism of action of the MAOIs is different from that of the other antidepressant drugs. You learned in Chapter 17 that most antidepressants act by blocking the pumps for neurotransmitters at the nerve endings. As a result, the levels of the chemical transmitters such as serotonin, norepinephrine, or dopamine build up in the synaptic regions. In contrast, the MAOIs seem to work by preventing the breakdown of chemical messengers within the nerves. As a result, levels of serotonin, norepinephrine, and dopamine build up inside the nerve terminals and these messengers are released into the synapses in much higher concentrations when the nerves fire. This results in a greater stimulation of the nerves at the other side of the synaptic junctions.

The MAOIs require careful medical management and close teamwork with your doctor. They are well worth the effort because they can sometimes lead to profound mood transformations, even when other drugs have been ineffective. Because they may cause increases in blood pressure, they are not usually recommended for individuals over sixty years of age or individuals with heart problems. In
addition, they are not usually prescribed for individuals with significant cerebrovascular disorders, such as strokes or aneurysms, or individuals with brain tumors. Paradoxically, though, they can sometimes be used with individuals with high blood pressure because they usually cause the blood pressure to fall.
¹⁹
Consultation with a cardiologist would be necessary to make sure there are no dangerous interactions with your other blood pressure medications.

Like other antidepressants, the MAOIs usually require at least two or three weeks to become effective. Your doctor will probably want to obtain a medical evaluation before starting you on this type of drug. This evaluation may include a physical examination, a chest X ray, an electrocardiogram, a blood count, blood chemistry tests, and a urinalysis.

Doses of MAOIs
. The doses of the MAOIs are listed in Table 20–1 on page 520. The two most commonly prescribed drugs for depression and anxiety are tranylcypromine (Parnate) and phenelzine (Nardil). One of the MAOIs, isocarboxazid (Marplan), is no longer available in the United States but is available in some other countries including Canada. In addition, selegiline (Eldepryl) is rarely used for depression but is often used in small doses (5 mg to 10 mg per day) in the treatment of Parkinson’s disease. It is just starting to be used for depression and some other psychiatric disorders, although in higher doses than for Parkinson’s disease, as indicated in Table 20–1. Although the Food and Drug Administration (FDA) has not yet approved selegiline for use in psychiatric disorders, recent studies indicate that it can also be effective for patients with atypical depression as well as those with chronic, severe depression.

A common prescribing error with the MAOIs is to give too big a dose too soon. For example, you will see in Table 20–1 on page 520 that the usual dose range for tranylcypromine (Parnate) is 10 mg to 50 mg per day. Some doctors prescribe larger doses, but I have seen many patients respond
to just one or two pills per day. Because the MAOIs can have some toxic side effects, I think it is prudent to start them at low doses, to increase very slowly, and not to push the dose too high. I usually start the patient on just one pill per day of an MAOI for the first week, and then increase to two pills per day. If the patient does not respond to a reasonable dose, say three or four pills per day of tranylcypromine or phenelzine, I usually do not increase the dose further but instead try an alternative medication along with a different psychotherapeutic strategy.

How long should you stay on an MAOI if it does not seem to be working? It seems obvious to me that if you have not had a fairly dramatic response after three or four weeks, as confirmed by your weekly scores on the mood test in Chapter 2, then you have probably given the drug a fair trial. You might respond better to another type of drug or to the cognitive therapy techniques described in this book.

How long should you stay on an MAOI if you do respond favorably? As with any antidepressant, you will have to discuss this with your physician, and many different approaches are currently in vogue. Some physicians believe that patients need antidepressants indefinitely to correct a “chemical imbalance,” but I have not usually found it necessary to keep patients on MAOIs or other antidepressants indefinitely. I have found that patients nearly always do well when they discontinue their MAOIs after a reasonable period of feeling good. Sometimes this may be as short as three months, sometimes as long as six to twelve months.

As with most antidepressants, you should taper off an MAOI gradually so there will be no withdrawal effects. Tapering too rapidly has caused some patients to experience sudden manic reactions. Suddenly going off selegiline can cause nausea, dizziness, and hallucinations, so one has to be especially careful to taper slowly.

What if you go off the MAOI and then get depressed again in the future? If you have responded to an MAOI in the past, you may respond more rapidly if you take the
same MAOI again in the future. In my practice I have had many patients who experienced a positive response to an MAOI (usually Parnate) and continued to feel undepressed for many years after they stopped taking the drug. Eventually, a few of them became depressed again and called for a “tune-up” appointment. I always gave them the first available appointments. If they sounded quite depressed, I told them to start the medication again. I also told them to start doing their psychotherapy homework again, especially the exercise of writing down and challenging their negative thoughts. When I saw them a few days later, many of them were already feeling better. Some of them told me that they began to improve in as little as one day or less when they took the MAOI for the second time. I believe that the medication as well as the cognitive therapy contributed to the rapid improvement.

I have not seen this rapid response with other types of antidepressants and do not know why it sometimes happens with MAOIs. Several patients explained that their bodies seemed to “recognize” the effects of the MAOI right away, especially the pleasurable stimulation that tranylcypromine (Parnate) causes. This helped them “remember” what it was like not to feel depressed. In a few cases, the improvement in mood came within an hour or two of the first pills they took. In the majority of cases, one or two cognitive therapy sessions seemed to reverse the relapse of depression.

Side Effects of MAOIs
. The most frequent side effects are listed in Table 20–7 on pages 572–573. As noted above, tranylcypromine (Parnate) tends to be stimulating. The stimulating effects of tranylcypromine (Parnate) can be especially helpful to depressed individuals who feel tired, lethargic, and unmotivated. Tranylcypromine (Parnate) may provide them with some much-needed “go power.” Because tranylcypromine (Parnate) tends to be stimulating, it can also cause insomnia. In order to minimize the insomnia, the entire dose can be taken once a day in the morning or
in divided doses in the morning and at noon. The latest recommended time to take tranylcypromine (Parnate) is 6:00
P.M.
Phenelzine (Nardil) is less stimulating than tranylcypromine (Parnate) and may be an attractive option for patients who feel too stimulated by tranylcypromine (Parnate).

The other side effects of the MAOIs are similar to those of the tricyclic and tetracyclic drugs described previously, but they are usually mild, especially when the MAOIs are taken in low doses. As you can see in Table 20–7, the MAOIs do not have strong effects on the muscarinic receptors (you will recall that these are also called cholinergic receptors). Consequently, they are not likely to cause dry mouth, blurred vision, constipation, or a delay in starting the urine flow. Weight gain also does not seem to be so much of a problem with these drugs, although some patients experience an increased appetite. Weight gain appears to be less of a problem with tranylcypromine (Parnate) than phenelzine (Nardil). Because tranylcypromine is stimulating, it may actually reduce your appetite, as do some of the SSRIs including fluoxetine (Prozac).

Some patients experience light-headedness when standing suddenly because these drugs have relatively strong effects on the alpha-adrenergic receptors. If dizziness does develop, the interventions described previously can help. These include: (1) ask your doctor if you can lower the dose—often you can still maintain the antidepressant effect; (2) get up more slowly and exercise your legs by walking in place immediately when you stand; (3) wear support stockings; (4) drink adequate fluids and make sure you eat enough foods with salt to maintain your body’s electrolytes.

Like most antidepressants, the MAOIs can sometimes cause a rash, although I do not recall ever seeing this. A loosening of the stool or constipation might also occur. Some patients report an upset stomach. Taking the medication with meals can alleviate this. Some patients report muscle twitches, but this is usually not dangerous. If you experience muscle pains, cramps, or tingling fingers—side effects I have never observed—a daily dose of 50 to 100
mg of vitamin B
₆
(pyridoxine) may help. This is because MAOI drugs may interfere with pyridoxine metabolism, so taking extra pyridoxine may compensate for this effect. Some doctors recommend taking vitamin B
₆
routinely if you are on an MAOI.