Feeling Good: The New Mood Therapy (70 page)

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A dash means that the incidence of this side effect was not greater than placebo.

^b
During the initial drug testing studies patients were not explicitly asked about sexual side effects. Consequently, the estimates of sexual side effects in the
PDR
are too low.

Some of the most common and troublesome side effects of the SSRIs include nausea, diarrhea, cramping, heartburn, and other signs of stomach upset. Approximately 20 percent to 30 percent of patients reported these symptoms in the earliest studies with the SSRIs.
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You will see in Table 20–5 that fluvoxamine (Luvox) is the most likely to cause constipation, whereas sertraline (Zoloft) is more likely to cause diarrhea. Patients taking paroxetine (Paxil) and sertraline (Zoloft) are more likely to complain of a dry mouth because of the anticholinergic effects of these drugs. In some studies, as many as 20 percent of the patients taking paroxetine (Paxil) reported dry mouth. (However, the percentages in the table are much lower because the placebo effects have been subtracted out.)

Most of these effects on the stomach and intestinal tract tend to occur in the first week or two and then disappear as the body adjusts to the medicine. In addition, if you start the SSRI at a low dose and then increase the dose gradually, these side effects are less likely to occur. It can also help if you take the medication with meals. (The tricyclic and tetracyclic drugs discussed in the previous section can also be taken with meals to minimize any adverse effects on the stomach and gastrointestinal tract.)

The SSRI drugs can occasionally cause headaches when you first start to take them. In Table 20–5 the rates for headache seem to be the highest for fluoxetine (Prozac) and fluvoxamine (Luvox); in contrast, the rates for citalopram (Celexa), paroxetine (Paxil), and sertraline (Zoloft) appear to be no greater than the rates of headaches reported by patients who take placebos. Excessive sweating has also been reported, especially with paroxetine (Paxil), but this is not usually severe. Patients taking high doses of the SSRIs may also complain of tremor, and this side effect seems to be equally common among all of the SSRI drugs.

Although initially reported as a “rare” side effect, it is now clear that delayed time to orgasm is quite common for men and women taking SSRIs. Some patients also complain of a loss of interest in sex or an inability to achieve an erection. These side effects were reported in fewer than 5 percent of patients during the premarketing research trials. However, now that the drugs are widely used, it has become clear that these side effects are far more common than reported in clinical trials and can occur in 30 percent or more of patients. The sexual side effects may be a reasonable trade-off if the drug helps you overcome your depression. Keep in mind that a loss of interest in sex can also be a symptom of depression itself. In addition, you will probably not need to stay on the drug indefinitely. Once you are feeling better and you stop taking the SSRI, your sexual functioning should return to normal.

You might wonder why these side effects were not noted in the premarketing research studies. At the 1998 Stanford
Psychopharmacology Conference, one of the speakers jokingly mentioned that the drug companies seem to have a “don’t ask, don’t tell” policy about certain kinds of adverse effects, including sexual side effects. I guess the idea is that what you don’t know won’t hurt you. I think this policy is unfortunate, because the FDA (and potential consumers) may be given an overly rosy picture about the effectiveness, side effect profile, and safety of a new drug. After the drug has been in widespread use for several years, a different picture often emerges.

The effects on sex are so predictable that one of these drugs, paroxetine (Paxil) is now recognized as an effective treatment for men who experience premature ejaculation (having orgasms too rapidly during sex). Some people do not experience a delayed orgasm on SSRIs. Others experience it but are not bothered, and some actually view it as a benefit. What is important is that if this feels like a problem for you, you should discuss it with your doctor before discontinuing the medication on your own. It might be possible to reduce the dose without a loss of the antidepressant effects.

Several drugs can be combined with an SSRI in an attempt to combat the sexual difficulties. Four which show promise include bupropion (Wellbutrin, in doses of up to 225 mg to 300 mg per day), buspirone (BuSpar; 15 to 30 mg per day), yohimbine (5 mg three times daily), or amantadine (100 mg three times daily).

Citalopram (Celexa), one of the newest SSRIs on the American market, may have fewer sexual side effects than the other SSRIs. You can see in Table 20–5 that it does appear to have fewer side effects in general than the other four SSRIs. In addition, there is the hope that it will be more effective for severe depressions than the SSRIs. It will be interesting to see if citalopram (Celexa) is more effective and does actually have fewer side effects after the drug has been in widespread use for a period of time. Sometimes marketing claims when drugs are first released turn out not
to be supported by clinical experience or by subsequent research by independent investigators.

Among the SSRIs, fluoxetine (Prozac) appears to be the most activating (stimulating), although fluvoxamine (Luvox) seems almost as likely to cause this side effect. Because fluoxetine (Prozac) is stimulating, it is sometimes given in the morning and at noon, rather than at bedtime. The stimulation can often be a benefit to depressed patients who feel tired, sluggish, and unmotivated. On the other hand, fluoxetine (Prozac) and fluvoxamine (Luvox) can also cause anxiety or jitteriness in as many as 10 percent to 20 percent of patients. These side effects can sometimes create additional difficulties for depressed patients who already have these kinds of symptoms.

The stimulating effects of fluoxetine (Prozac) are not necessarily bad, even for anxious patients. Anxiety and depression nearly always go hand in hand to a certain extent, and many patients need treatment for both kinds of problems. Patients with significant anxiety, such as chronic worrying, panic attacks, or agoraphobia, are often the ones who complain that fluoxetine (Prozac) makes them feel more nervous initially. I often tell these patients that the nervousness they feel is a good thing, because it shows the drug is working in the brain. I encourage them to stick with it, because in a few weeks or less they may notice a significant improvement in their depression as well as their anxiety. Most anxious patients have been able to stick with the fluoxetine (Prozac), and the predicted improvement often does occur. This illustrates how a positive attitude can sometimes help patients overcome drug side effects.

Although any of the SSRIs can cause trouble with sleeping, not all of them are as stimulating as fluoxetine (Prozac). In fact, paroxetine (Paxil) and fluvoxamine (Luvox) can be quite sedating for some patients. In other words, these drugs will tend to relax or tire you, instead of stimulating you the way fluoxetine (Prozac) does. In fact, paroxetine
(Paxil) is sometimes given two hours before bedtime so that the maximum sleepiness will occur at the time that you ordinarily go to sleep. Paroxetine (Paxil) or fluvoxamine (Luvox) might be good choices if insomnia is a major aspect of your depression. Note, however, that patients taking paroxetine (Paxil) are also somewhat more likely to complain of weak or fatigued muscles. Citalopram (Celexa) and sertraline (Zoloft) appear to be halfway in-between—they do not typically cause excessive stimulation or sedation, but are more neutral in this respect.

In the section below on serotonin antagonists, I will describe an antidepressant called trazodone (trade name Desyrel) which has calming, sedative properties. Trazodone can be given in small doses (50 to 100 mg at bedtime) to patients who are taking SSRIs. This has three potential benefits: (1) the calming effects of trazodone will reduce the nervousness caused by the SSRIs; (2) the trazodone can be given at bedtime to improve sleep; (3) trazodone may sometimes boost the antidepressant effects of the SSRI and increase the likelihood of recovery.

In spite of these advantages, I usually try to treat patients with one drug at a time. This avoids any extra side effects and minimizes the possibility of adverse drug interactions. In my experience, treatment with one drug at a time is usually successful. If you reduce the dose of any SSRI, you can often minimize the side effects without having to add additional drugs. I will address the problem of using more than one drug at the same time toward the end of this chapter.

For example, if you are starting fluoxetine (Prozac) and you are bothered by nervousness, insomnia, or upset stomach, you can take a lower dose and increase the dose more gradually. In addition, if you have been on fluoxetine (Prozac) for several weeks or more, there is an excellent chance you can reduce the dose, often quite dramatically. This will often minimize the side effects without interfering with the antidepressant effects of this drug. As noted above, this is because levels of fluoxetine (Prozac) build up after a period
of time, so the same dose may produce far more side effects because your blood level has become so much higher. There is really no need for large doses or excessively high blood levels of any of the SSRIs, because low doses have been shown to be just as effective as high doses.

SSRI Drug Interactions
. A number of common drug interactions for the SSRIs are listed in Table 20–6 on pages 560–563. You will see in Table 20–6 that many other psychiatric drugs can interact with the SSRIs, including antidepressants, major and minor tranquilizers, and mood stabilizers. Important interactions with nonpsychiatric drugs are also listed. If you are taking an SSRI and one or more additional drugs at the same time, it would be wise to review this table. Make sure you also ask your physician and pharmacist if there are any drug interactions you should be aware of. This includes prescription drugs as well as nonprescription drugs that are sold over the counter.

As you can see, SSRIs have a tendency to cause the blood levels of other antidepressants to increase. This is because the SSRIs slow down the metabolism of these other drugs in the liver, as discussed in Chapter 19. In some cases, this could be dangerous. For example, the combination of an SSRI with a tricyclic antidepressant can potentially cause abnormal heart rhythms. Although this complication is rare, the effects on the heart can be serious. The combination of an SSRI with bupropion (Wellbutrin) can increase the risk of seizures—an uncommon but serious side effect of bupropion. However, as noted above, bupropion is often added to an SSRI in low doses to try to minimize the sexual side effects of the SSRIs. This can usually be done safely. Make sure you inform your physician if you have any history of head trauma or seizures, because this particular drug combination may not be advisable for you.

As mentioned in Chapter 19, the interaction of an SSRI with an MAOI antidepressant is extremely dangerous regardless of the dose of either drug. This combination should be avoided because it can result in the potentially lethal “serotonin syndrome” described in Chapter 19. In addition, remember that both the SSRIs and the MAOIs can require a considerable period of time to clear out of your body after you have stopped taking them. If you stopped taking Prozac and then started an MAOI several weeks later, it could trigger the serotonin syndrome because Prozac would still be present in your bloodstream. Similarly, if you were to start Prozac within two weeks of stopping an MAOI, this might also trigger the serotonin syndrome. The effects of the MAOIs last only one to two weeks, so you will not have to wait as long when you switch from an MAOI to an SSRI as when you switch in the opposite direction.

Table 20–6.
Drug Interaction Guide for SSRI Antidepressants.
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