Feeling Good: The New Mood Therapy (77 page)

But let’s see what happens in a real-life situation. Suppose your dose is 75 mg per day. You could take either one of the regular 37.5 mg pills in the morning and a second 37.5 mg pill in the evening, for a total cost of $2.17 per day, or one of the 75 mg extended-release pills once per day. As noted above, the cost of the 75 mg extended-release pills will also be $2.17 per day. Either way, Effexor is very expensive, since the daily dose may be as high as 375 mg per day. The high price is especially striking when you compare the cost of Effexor with the cost of many of the generic tricyclic antidepressants that are just as effective and available for less than ten cents per day.

As with any antidepressant, it is best to taper off venlafaxine
slowly. At least two weeks are recommended, and some patients may require as much as four weeks.

Side Effects of Venlafaxine
. The side effects of venlafaxine are listed in Table 20–11 on pages 608–609. As you can see, they are similar to the SSRI compounds described above. The most common side effects of venlafaxine are nausea, headache, sleepiness, insomnia, abnormal dreams, sweating, nervousness, and tremor. Venlafaxine can also cause the same types of sexual difficulties as the SSRIs, including a loss of interest in sex and difficulties achieving orgasm. These sexual side effects tend to be quite common, just as with the SSRIs. In spite of the claim that venlafaxine has fewer side effects than the older tricyclic antidepressants, this drug can nevertheless cause dry mouth and dizziness in some patients. The dizziness is particularly likely if you go off the drug too quickly.

One distinct type of side effect seen with venlafaxine is an increase in blood pressure. However, the blood-pressure increases are typically seen only at higher doses (225 mg per day or above). Nevertheless, if you have problems with your blood pressure, you and your doctor should monitor your blood pressure carefully, and this drug may not be a good choice for you. At doses less than 200 mg per day, the likelihood of an increase in blood pressure is only about 5 percent. The probability increases to 10 percent or 15 percent at doses greater than 300 mg per day. Blood-pressure increases of 20 to 30 mm of mercury have been observed, for example.

Drug Interactions for Venlafaxine
. Because venlafaxine is relatively new, information about its interactions with other drugs is still relatively limited. Venlafaxine appears to be less likely to interact in adverse ways with other medications you are taking. Several drugs may cause blood levels of venlafaxine to increase, and so lower doses of venlafaxine may be needed. These include:

Venlafaxine may cause the blood levels of several of the major tranquilizers to increase. These include trifluoperazine (Stelazine), haloperidol (Haldol), and risperidone (Risperdal), and so lower doses of these drugs may be needed. In theory, these drugs could also cause blood levels of Venlafaxine to increase.

Venlafaxine must not be combined with MAOI antidepressants because of the danger of the serotonin syndrome (hyperpyretic crisis) described on page 576. Remember that it takes up to two weeks for the effects of an MAOI to clear out of your body, so a two-week drug-free period will be required if you stop taking an MAOI and then start taking venlafaxine. In contrast, if you go off venlafaxine and then start taking an MAOI, a one-week drug-free period should be sufficient, because venlafaxine leaves the body fairly rapidly.

Mirtazapine (Remeron) was released in the United States in 1996. It also enhances both norepinephrine and serotonin activity, but through a different mechanism from venlafaxine. Premarketing studies suggest that mirtazapine may be effective for mildly depressed outpatients and for more severely depressed inpatients as well. It may also be particularly helpful for depressed patients who are very anxious or nervous.

Doses of Mirtazapine
. The dose range for mirtazapine is 15 to 45 mg per day. Most physicians will prescribe a smaller amount at first (7.5 mg per day) and then slowly increase the dose. Because mirtazapine causes sleepiness in
more than 50 percent of the people who take it, it can be given once a day at bedtime, usually in doses of 15 to 45 mg per day. Some physicians report that mirtazapine is less likely to cause less sleepiness when the dose is increased. This is the opposite of what you might expect intuitively. It is because the drug may have some stimulating effects at the higher doses. We will have to wait until there is more clinical experience with this drug to see if this is really true.

Side Effects of Mirtazapine
. The side effects of mirtazapine are listed in Table 20–11 on pages 608–609. You can see that it blocks the histaminic, alpha-adrenergic, and muscarinic receptors in much the same way that the older tricyclic antidepressants do. Therefore, the side effect profile of mirtazapine is very similar to the tricyclics, especially amitriptyline, clomipramine, doxepin, imipramine and trimipramine (see Table 20–2). The more common side effects include tiredness (54 percent of patients) noted above, increased appetite (17 percent), weight gain (12 percent), dry mouth (25 percent), constipation (13 percent), and dizziness (7 percent). Keep in mind that these figures are somewhat inflated because they do not take into account the placebo effect. For example, 2 percent of patients on placebo also report weight gain, and so the true incidence of weight gain that can be attributed to the mirtazepine would be 12 percent minus 2 percent, or 10 percent. Mirtazepine is not likely to cause the stomach upset, insomnia, nervousness, and sexual problems commonly seen with the SSRIs such as Prozac.

Mirtazapine has some unique adverse effects not shared with other antidepressants. It can, in rare cases, cause your white blood cell count to fall. Because these cells are involved in fighting off infections, this could make you more vulnerable to a variety of infections. If you develop a fever while taking this drug, make sure you contact your physician immediately so that he or she can obtain a complete blood count. Mirtazapine can sometimes cause an increase in levels of blood fats such as cholesterol and triglycerides.
This could be a problem if you are overweight or have a heart condition or if your cholesterol and triglycerides levels are already elevated.

Drug Interactions for Mirtazapine
. Because mirtazapine is relatively new, very little information about its drug interactions is available. It must not be combined with the MAOI antidepressants because of the risk of the serotonin syndrome (hyperpyretic crisis). Because it can be quite sedating, it will enhance the effects of other sedative drugs. These include alcohol, major and minor tranquilizers, sleeping pills, some antihistamines, barbiturates, many other antidepressants, and the antianxiety drug buspirone (BuSpar). The increased sleepiness you experience when these substances are combined with mirtazapine could lead to difficulties with coordination and concentration. This might be hazardous when driving or operating dangerous machinery.

In 1949, an Australian psychiatrist named John Cade observed that lithium, a common salt, caused sedation in guinea pigs. He gave lithium to a patient with manic symptoms and observed dramatic calming effects. Tests of the effects of lithium in other manic patients yielded similar results. Since that time, lithium has slowly gained popularity throughout the world. It has been used successfully in the treatment of a number of conditions, including:

You should keep in mind that in all of these conditions, lithium is sometimes helpful but rarely ever curative. Like most medications, it is a valuable tool but not a panacea.

As noted above, manic-depressive illness is sometimes also called bipolar illness. “Bipolar” simply means “two poles.” Patients with bipolar illness experience uncontrollable euphoric mood swings that often alternate with severe depressions. The manic phase is characterized by an extremely ecstatic, euphoric mood, inappropriate degrees of self-confidence and grandiosity, constant talking, nonstop hyperactivity, increased sexual activity, a decreased need for sleep, heightened irritability and aggressiveness, and self-destructive impulsive behavior such as reckless spending binges. This extraordinary disease usually develops into a chronic pattern of uncontrollable highs and lows that can come on unexpectedly throughout your life, so your physician may recommend that you continue to take lithium (or another mood stabilizing drug) for the rest of your life.

If you have experienced abnormal mood elevations along with your depression, your physician will almost definitely prescribe lithium or another comparable mood-stabilizing drug. Some studies suggest that if you are depressed and have a definite family history of mania, you might benefit from lithium even if you have never been manic yourself. However, most physicians would first prescribe a standard antidepressant and observe you carefully. Although antidepressants do not usually cause euphoria or mania in people with depression, they can occasionally have this effect in individuals with bipolar manic-depressive illness. The mania can begin as quickly as twenty-four to forty-eight hours after starting the antidepressant.

In my clinical practice, the development of a sudden and dangerous manic episode after starting an antidepressant has been quite rare, even in patients with bipolar illness. Nevertheless, if you have a personal or family history of
mania, it is conceivable that you could experience this side effect. Be sure to tell your doctor about this so you can receive careful follow-up after starting an antidepressant. Your family, too, should be alerted to this possibility. Family members are often aware of the development of a manic episode before the patient realizes what is happening, and can alert the doctor that a problem has developed. This is because the distinction between normal happiness and the beginning of the mania may be unclear to the patient. Furthermore, mania feels so good at first that you may not recognize it as a dangerous side effect of the medication you are taking.

Doses of Lithium
. As you will see in Table 20–1, lithium comes in 300-mg dosages, and normally three to six pills per day in divided doses are required. Your physician will guide you. Initially, you may take the lithium three or four times per day. Once you are stabilized on lithium, you may be able to take half your total daily dose in the morning and half before you go to bed. This twice-a-day schedule will be more convenient.

Sustained-release capsules containing 450 mg are also available. Because these drugs are released more slowly in the stomach and gastrointestinal tract, they may cause fewer side effects and they are more convenient because you don’t have to take them so often. However, their increased cost, as compared with generic lithium, may not justify taking them. Furthermore, many patients have reported that the side effects of the inexpensive, generic brands of lithium are no different from the more expensive slow-release brands.

Like the other drugs used for treating mood disorders, lithium usually requires between two and three weeks to become effective. When taken for a prolonged period of time, its clinical effectiveness seems to increase. Thus, if you take it for a period of years, it may help you more and more.

Unfortunately, there appears to be a group of individuals
who do well on lithium, stop taking it, become symptomatic again, and then find that the lithium is less effective when they start taking it again. This is one reason why you should not stop taking lithium, or any other medication, without first consulting with your doctor.