Feeling Good: The New Mood Therapy (67 page)

You and your doctor may prefer to build up the dose a bit more gradually. Doses of up to 150 mg per day can be conveniently taken once a day at night. The antidepressant effect will last all day long, and the most bothersome side effects will occur at night, when they will be least noticed. If doses larger than 150 mg per day are required, the additional medicine should be given in divided doses during the daytime.

For the more sedating tricyclic antidepressants, up to half the maximum indicated dose may be taken on a once-per-day basis before bedtime. This dosage promotes sleep. Several of the tricyclic antidepressants, including desipramine, nortriptyline, and protriptyline, can be stimulating. They can be taken in divided doses in the morning and at noon. If taken too late in the day, they may interfere with sleep.

If you reduce the dose of a tricyclic antidepressant or if you decide to stop taking the medicine, it is best to reduce the dose gradually and never abruptly. Sudden discontinuation of any antidepressant may result in side effects. These include upset stomach, sweating, headache, anxiety, or insomnia. Usually, you can go off a tricyclic antidepressant safely and comfortably by tapering the dose gradually over a one- or two-week period.

Side Effects of the Tricyclic Antidepressants
. The most frequent side effects of the tricyclic antidepressants are listed in Table 20–2 on pages 530–532. You will see in this table that all the tricyclic antidepressants have quite a number of side effects, and this is their greatest drawback.
The most common side effects include sleepiness, dry mouth, a mild hand tremor, temporary light-headedness when you suddenly stand up, weight gain, and constipation. They can also cause excessive sweating, difficulties with sex, twitches or jerking when you fall asleep at night, and a number of other effects listed in Table 20–2. Most of these side effects are not dangerous, but they can be annoying.

You learned earlier that the side effects of antidepressant drugs can be predicted if you know how strongly they block histamine receptors, alpha-adrenergic receptors, and muscarinic receptors (also called cholinergic receptors) in the brain. You can see from Table 20–2 that each antidepressant has a different profile of side effects depending on its action on these three receptor systems in the brain.

Blockade of the brain’s histamine receptors makes you hungry and sleepy. Table 20–2 indicates that four of the tricyclic antidepressants (amitriptyline, clomipramine, doxepin, and trimipramine) have rather strong effects on the histamine receptors. Consequently, these four antidepressants are more likely to make you feel sleepy and hungry. If you are having trouble sleeping, this side effect could be a benefit, but if you are already feeling sluggish and unmotivated, these drugs may make things worse for you. If you have been losing weight due to depression, the appetite boost could be beneficial. However, if you are overweight, you might have to pay more attention to your diet and exercise more in order to avoid weight gain, which can be demoralizing. Since there are now many available antidepressants that do not cause weight gain, it might be better to switch to one of them. You can see in Table 20–2 that three of the tricyclics (desipramine, nortriptyline, and protriptyline) have only weak effects on the histamine receptors. These antidepressants will be less likely to cause sleepiness and weight gain. There are many antidepressants in other categories as well that do not cause sleepiness and weight gain.

You may also recall that blockade of the brain’s alphaadrenergic receptors causes a drop in blood pressure. This can result in temporary light-headedness or dizziness when
you suddenly stand up because your leg veins become more relaxed, and blood temporarily pools in your legs. As a result, your heart temporarily does not have enough blood to pump up to your brain, and so your vision may get black and you may feel dizzy or woozy for a few seconds. Antidepressants with relatively strong effects on the brain’s alpha-adrenergic receptors will be more likely to cause dizziness when you suddenly stand up. You will see in Table 20–2 that many tricyclics have strong effects on alpha-adrenergic receptors, but that two of them (desipramine and nortriptyline) have only weak effects on them. Consequently, these two drugs are less likely to cause dizziness or a drop in blood pressure.

Finally, blockade of the brain’s muscarinic receptors causes side effects such as dry mouth, constipation, blurred vision, difficulties getting your urine flow started, and a speeding up of the heart, even when you are resting. Because of these effects on the heart, the tricyclic medications in Table 20–2 with the strongest effects on-these muscarinic receptors may not be advisable for patients with cardiac problems. Drugs with strong anticholinergic effects can also create problems with memory. Many patients have told me that they cannot remember a word they want to use, or they forget someone’s name when they take these drugs. The memory effects are dose-related and should disappear when you stop taking the drug.

You can see that two of the tricyclic drugs in Table 20–2 (desipramine and nortriptyline) have relatively weak anticholinergic effects. These two drugs will be the least likely to cause side effects like dry mouth and forgetfulness. These two also tend to have weaker effects on the histamine and alpha-adrenergic receptors. Because they have fewer side effects, they are among the most popular tricyclic antidepressants.

The effects of antidepressant drugs on these three brain receptor systems do not completely explain all their side effects. In the right-hand column, I have listed many of the more common or significant side effects for each drug. For example, you will see that some of them can cause skin rashes. Some tricyclics, most notably clomipramine (Anafranil), can cause seizures, and so this drug would not be a good choice for individuals with epilepsy.

Table 20–2.
Side Effects of Tricyclic Antidepressants
^a

^a
The + 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.

^b
Many side effects, if troublesome, can be minimized by a reduction in dosage. Side effects are usually greatest in the first few days and tend to disappear later.

^c
The drugs that are the most sedative may also have greater antianxiety effects. In other words, they may calm you and make you less nervous. When given at night, the sedative agents help reduce insomnia.

If you and your doctor are choosing one of the antidepressants listed in Table 20–2, you might want to consider the side-effect profile when making your choice. This is because all these medications are comparably effective, so their side effects may be the most important criteria for you in deciding among them. So if you are having trouble sleeping at night, one of the more sedative antidepressants may be useful. These sedative agents are also somewhat calming and so they might be helpful if you are experiencing anxiety.

Many of the side effects of the tricyclic antidepressants listed in Table 20–2 occur in the first few days. With the exception of dry mouth and weight gain, these side effects frequently diminish as you become accustomed to the drug. If you can simply put up with the side effects, many of them will disappear after a few days. If the effects are strong enough to make you uncomfortable, your doctor may decide to reduce the dose, which usually helps.

Some side effects suggest you are taking an excessive dose. These 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. As noted above, light-headedness is most likely to occur when you stand up suddenly, because the blood flow to your brain is temporarily diminished. The dizzy feeling usually persists for only 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. The movement of your legs causes your leg muscles to “pump” the blood back up to your brain. Support stockings can also help.

Some patients describe feeling “strange,” “spaced out,” or “unreal” for several days when they first start taking a
tricyclic antidepressant. In my experience, one of the tricyclics called doxepin (Sinequan) seems more likely to cause this “spaced out” effect. When patients report feeling strange on the first day or two of taking an antidepressant, I usually advise them to stick with it. In nearly all cases the sensation disappears completely within a few days.

If you give patients sugar pills (placebos) they think are antidepressants, they will also report side effects that are similar to the side effects reported by patients taking antidepressants. For example, in one study, 25 percent of the patients taking clomipramine reported difficulties sleeping, so you might conclude that this drug causes insomnia in a quarter of those who take it. However, 15 percent of the patients in the same study who received only placebo also reported insomnia. So the likelihood of insomnia actually caused by clomipramine would be 25 percent minus 15 percent, or 10 percent. Clearly, this side effect is “real,” but it is somewhat less common than you might at first expect.

Such studies indicate that many “side effects” may not actually be caused by the medication you are taking. Some side effects may result from fears about the medication, or from the depression itself, or from other stressful events in your life such as a conflict with your spouse, rather than from the drug itself.

Side Effects of the Tetracyclic Antidepressants
. You can see in Table 20–3 on pages 536–537 that the side effects of the tetracyclic antidepressants are similar to those of the tricyclic antidepressants. However, they have some special side effects of their own that should be considered if you are taking one of these drugs. Maprotiline (Ludiomil) appears to be more likely than the eight tricyclic antidepressant drugs to cause seizures, a particularly troublesome side effect. Although the likelihood of seizures is low, patients with a history of seizures or head trauma should probably avoid this drug. Recent studies suggest that the likelihood of seizures with maprotiline is significantly
greater when the dose is increased too rapidly, or when patients are kept on higher-than-recommended doses (225 to 400 mg per day) for more than six weeks.
¹⁶
Therefore the manufacturer has suggested that maprotiline should be started and increased very slowly, and that the dose should be maintained at no more than 175 mg per day if patients take this drug for more than six weeks.