Feeling Good: The New Mood Therapy (83 page)

Weather, your personal habits, or other medications you are taking can sometimes influence blood levels of antidepressants or mood stabilizers. For example, if you are sweating a great deal during the summer, your blood level of lithium may rise, so your doctor may need to reduce the dose. If you are a smoker, your body will break down tricyclic antidepressants more rapidly because of the effects of the nicotine. Consequently, you may need a higher dose of these antidepressants. Many other drugs that can also cause a rapid breakdown of tricyclic antidepressants are listed in Table 20–5. In contrast, some drugs on this table can slow the metabolism of tricyclic antidepressant drugs by the liver, leading to excessively high blood levels of the antidepressants. Remember that these drug interactions can work both ways: an antidepressant or mood stabilizer may affect the level or activity of other drugs you are taking, and vice versa.

Before you and your doctor decide that a particular drug is not working, make sure that you review the dose with him or her. Ask about the possibility of drug interactions if you are taking more than one drug. Your doctor may want to order a blood test to ensure that the level in your blood is adequate. Blood-level testing is more commonly done for the mood stabilizers and for the tricyclic and tetracyclic drugs than for other types of antidepressants listed in Table 20–1.

If the blood level is adequate and you have been taking the medication for a sufficient period of time but your antidepressant is still not working, your doctor may try switching you to a different type of antidepressant or may try an augmentation strategy. This involves adding a small dose of a different drug to try to boost the effect of the antidepressant. Several kinds of augmentation strategies currently in vogue are listed in Table 20–16 on pages 664–669. A complete discussion is beyond the scope of this book; I will describe just a couple of them to give you a feel for this approach. Interested readers may want to consult the excellent reference by Schatzberg and his colleagues.
¹

Two drugs commonly used for antidepressant augmentation are lithium, a drug you’ve learned about in this chapter, and a thyroid hormone called liothyronine (also known as Cytomel, or T
₃
). Your doctor may add 600 mg to 1,200 mg per day of lithium carbonate or 25 to 50 micrograms per day of liothyronine to your antidepressant for several weeks if the antidepressant has not been working adequately. As noted above, lithium is usually used to treat bipolar (manic-depressive) illness, and liothyronine is used to treat people with underactive thyroid glands. However, in this case, the goal is different—the purpose of adding a small dose of lithium or liothyronine is to make the antidepressant more effective. It is not clear why lithium and liothyronine sometimes have this effect of boosting the effectiveness of antidepressants.

A liothyronine trial will usually last for one to four weeks. If you respond positively, your physician may continue the liothyronine for two more months. Then she or he will probably taper you off the augmentation medication over one to two weeks.

The dose of lithium used for augmentation will be adjusted with a blood test so that your blood level will remain in the range of around 0.5 to 0.8 mEq per L. These levels are a little lower than the levels used to treat patients who
are experiencing mania. The lower levels have the advantage of having fewer side effects. The lithium augmentation trial will generally last for two weeks. Positive results have been reported when lithium was combined with tricyclics, SSRIs, and MAOIs. Research studies suggest that as many as 50 to 70 percent of patients who do not respond to an antidepressant will respond more favorably when lithium is added. If there is no improvement in your depression, your doctor will probably discontinue the lithium as well as the antidepressant and try another medication.

Some doctors use antidepressant combination therapy for patients with difficult depressions. For example, one new approach is to add an SSRI when a tricyclic does not work, or to add a tricyclic when an SSRI does not work. This combination can cause large increases in the blood level of the tricyclic medication, and so your doctor may decrease the tricyclic first and then check your tricyclic level with a blood test after you start the SSRI. Your doctor may also order an ECG to make sure there are no adverse effects on your heart.

An MAOI might also be combined with a tricyclic antidepressant as a combination antidepressant strategy. This is an advanced form of treatment for the specialist and requires careful teamwork between you and your doctor. You will recall that dangerous reactions can result from combining MAOIs with other antidepressant drugs or with lithium. Although the
Physician’s Desk Reference
advises against such drug combinations, Schatzberg and colleagues report that the combination can be safe and helpful to some patients who fail to respond to single medications.
¹
To maximize safety, these investigators recommend: (1) the MAOI and tricyclic should be started at the same time; (2) clomipramine should be avoided; (3) the safest tricyclics to use in combination with MAOIs appear to be amitriptyline (Elavil) and trimipramine (Surmontil); (4) among the two commonly prescribed MAOIs, phenelzine (Nardil) appears to be safer than tranylcypromine (Parnate) to use in combination with a tricyclic.

Table 20–16
. Antidepressant Augmentation Chart.

You will see quite a number of additional augmentation strategies listed in Table 20–16. My experience with these antidepressant combination and augmentation strategies has been limited, but I have not been impressed with the results. I have tried lithium or thyroid augmentation with a number of patients but none of them seemed to improve. I was not encouraged to continue with this approach. However, if a depressed patient has failed to respond to an adequate trial of several antidepressants, one at a time, from different chemical classes, then a combination of antidepressants or an augmentation strategy might be worth a try.

If you have received an adequate dose of an antidepressant for an appropriate period of time and you are not responding, what antidepressant should you try next? Many physicians will switch you to an antidepressant of a completely different class to maximize the chance of a positive response. This idea makes good sense, since the different antidepressants have slightly different effects on the brain. If you have failed to respond to an SSRI such as fluoxetine (Prozac), your doctor may want to try a tricyclic such as imipramine (Tofranil), for example. Prozac selectively activates the serotonin systems in the brain, whereas imipramine has effects on many different systems.

If you switch to another drug, you will usually need to taper off your current drug slowly so as to prevent any withdrawal effects. Antidepressants are not addictive and they do not cause craving when you stop taking them. However, they need to be discontinued slowly to prevent uncomfortable withdrawal reactions. For example, the tricyclics can cause insomnia and upset stomach if you go off them abruptly, as noted previously.

Further, as noted above, there may be a mandatory waiting period when you are switching from one drug to another. This is because the two drugs might be dangerous if mixed together, and the effects of the first drug may persist for a while after you have stopped taking it. The classic example would be switching from an SSRI, such as fluoxetine (Prozac), to an MAOI, such as tranylcypromine (Parnate). The combination of these two drugs can cause the
previously described serotonin syndrome, which is occasionally fatal. In addition, both types of drugs clear out of the body slowly, and so a drug-free period is necessary before switching from one to the other. When switching from Prozac, an SSRI, to Parnate, an MAOI, this waiting period may be five weeks or more. When switching from Parnate to Prozac, the waiting period will be at least two weeks. With some combinations of drugs, however, a waiting period is not necessary. Check with your doctor about this.