Feeling Good: The New Mood Therapy

by Burns, David D.

  bThis 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.

  MAO Inhibitors

  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:

  • overeating (as opposed to a loss of appetite in classic depression);

  • fatigue and sleeping too much (rather than trouble with sleeping);

  • irritability or hostility (in addition to the depression);

  • extreme sensitivity to rejection.

  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 believ
e 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 B6 (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 B6 routinely if you are on an MAOI.

  The MAOIs can sometimes interfere with sexual functioning, especially in higher doses. Some patients experience a decreased interest in sex and difficulties maintaining an erection or achieving orgasm. In this regard, the MAOIs are a lot like the SSRIs described previously. The sexual side effects may result from their effects on the serotonin receptors in the brain, but this is not known for sure. Although the sexual side effects can be disconcerting, these difficulties may be a worthwhile trade-off if the medication is having a beneficial effect on your mood. You should be reassured that the sexual side effects are dose-related and usually disappear entirely when you are no longer taking the MAOI.

  One young man I treated actually found the sexual side effects to be helpful. He reported that he had always had a problem with premature ejaculation. Once he started taking tranylcypromine (Parnate), the problem disappeared. In fact, he reported he could make love for prolonged periods without any danger at all of having a premature orgasm. He said his girlfriend thought this was a great miracle, and he advised me to buy stock in the company that manufactured the drug!

  One pleasurable side effect of an MAOI is an excessively positive reaction to the drug. In other words, quite a number of patients not only overcome their depressions but begin to feel euphoric or high. This is not necessarily bad, but in some cases may become so extreme that the patient experiences the symptoms of mild mania. In the rare patient with a history of bipolar manic-depressive illness (patients with previous extreme highs and lows that were not caused by drugs or alcohol), there is the possibility that an MAOI might trigger a full-blown manic episode. This is actually true of most antidepressants, and not just the MAOIs.

  Table 20–7. Side Effects of Monoamine Oxidase Inhibitorsa

  aThe + to + + + ratings in this table refer to the likelihood that a particular side effect will develop. The actual intensity of the side effect will vary among individuals and will also depend on how large the dose is. Reducing the dose can often reduce side effects without reducing effectiveness.

  bMany of the side effects of the MAOIs can often be reduced or eliminated by reducing the dose. They usually have very few side effects, and can often be quite effective, at small doses.

  cThis is because this drug is usually prescribed for patients with Parkinsonism who take many other drugs, and also have many symptoms due to their illness. Therefore, it is difficult to determine how frequently selegiline would cause side effects in depressed individuals. At higher doses, the side effects of selegiline are probably very similar to the other MAOIs.

  If you do start to feel unusually happy, it would be wise to keep in touch with your prescribing doctor to make sure these feelings do not get out of hand. In my experience, this is not usually a serious problem—the euphoric feelings provide a welcome relief from the depression and tend to diminish in a week or so. The euphoric feelings also respond to a reduction in dose.

  Dr. Alan Schatzberg and his colleagues1 have pointed out that some patients may seem drunk or intoxicated when taking MAOIs. Patients may also feel confused and have trouble with coordination. These
adverse reactions are more likely when the doses are pushed to very high levels. Obviously, the dose should be reduced immediately if these toxic effects develop. I have personally never seen these effects because I have never pushed the doses of MAOIs to unusually high levels.

  Two of the MAOI drugs, phenelzine (Nardil) and isocarboxazid (Marplan), can have negative effects on the liver. Therefore, your doctor may want to do a blood test to monitor levels of certain enzymes that reflect liver function before you start these drugs, and then again every few months while you are taking them. Patients with liver disease or abnormal liver function tests are usually advised not to take any of the MAOIs, including tranylcypromine (Parnate).

  Dr. Alan F. Schatzberg and his colleagues1 have pointed out that selegiline (Eldepryl) may have fewer side effects than the other MAOI drugs, at least at low doses. At low doses, selegiline seems less likely to cause dizziness when standing, sexual problems, or difficulties sleeping. However, selegiline is much more expensive than the other MAOIs, and in most cases the other MAOIs will do the job just as effectively. In addition, the side effects of all the MAOI antidepressants tend to be minimal at lower doses. In my experience, many patients have responded favorably to low doses of the MAOIs, so selegiline may not really have any significant advantages over the two older and cheaper drugs.

  As you will learn next, all the MAOIs can cause dangerous blood pressure elevations when patients ingest the forbidden foods. Selegiline is less likely to have this effect, but only if the selegiline is taken in small doses (10 mg per day or less). Larger doses of selegiline are often needed for psychiatric problems. At these higher doses it is necessary to observe the same dietary precautions that you would observe with any of the MAOIs. This is unfortunate because it was initially hoped that depressed patients would be able to take selegiline and not have to restrict their diets so religiously.