What Are the Most Common Side Effects of the Antidepressants?
As discussed in Chapter 17, all the medications prescribed for depression, anxiety, and other psychiatric problems can cause different kinds of side effects. For example, many of the older antidepressants (such as amitriptyline, trade name Elavil) cause fairly noticeable side effects such as dry mouth, sleepiness, dizziness, and weight gain, among others. Many of the newer antidepressants (such as fluoxetine, trade name Prozac) can cause nervousness, sweating, upset stomach, or a loss of interest in sex as well as difficulties having an orgasm.
I will describe the specific side effects of every antidepressant in Chapter 20. You will see that some medications produce lots of side effects whereas others produce very few.
The Side Effects Checklist on pages 494–496 can provide you and your physician with extremely accurate information about any side effects that you experience while you are taking a medication. If you take this test a couple times per week, this will show how the side effects change over time.
Remember, however, that many of these so-called side effects can occur even if you are not taking any medication, since many side effects are also symptoms of depression. Feeling tired, having trouble sleeping at night, or a loss of interest in sex would be good examples. So it can be very useful to complete the Side Effects Checklist at least once or twice before you start any medication. That way, you can see if a side effect began before or after you started the drug. Obviously, if you had the same side effect before you started taking a drug, then the drug is probably not to blame for it.
It is also good to remember that patients who only take placebo medications (sugar pills) during research studies tend to report lots of side effects. This is because they think they are taking a real drug. So there is no proof that a particular side effect is necessarily caused by the drug you are taking. When in doubt, talk this over with your physician.
Let me give you a particularly vivid example of how the mind can occasionally play tricks on us. I once treated a high school teacher for depression. She was not responding well to the psychotherapy and I had the hunch that she would respond to a particular antidepressant drug called tranylcypromine (Parnate) that is described in Chapter 20. However, she was somewhat stubborn and had a strong fear of taking any medication. She complained that she would not be able to tolerate the side effects. I explained that I planned to prescribe a low dose and that in my experience most patients did not have many side effects with this medication, especially when the dose was low. But my efforts were to no avail—she insisted the side effects of the drug would be unbearable, and refused to accept a prescription.
Side Effects Checklist*
Please describe any other side effects: _________________________
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*Copyright © 1998 by David D. Burns, M.D.
I asked if she would be willing to do a little experiment to check this out. I told her I would give her two weeks’ worth of pills in fourteen separate envelopes. Each envelope was labeled with the date and day of the week she was to take the pills inside it. I explained that some envelopes would contain placebo pills that could not have any side effects whatsoever. Half the pills would be yellow and half would be red, but she would not know whether she was taking the real medication or a placebo on any given day. The envelope for the first day contained one yellow pill and the envelope for the second day contained one red pill. The envelopes for the third and fourth days contained two yellow pills each, and the envelopes for the fifth and sixth days contained two red pills each. Finally, each envelope for the second week contained three yellow pills or three red pills.
I asked her to complete the Side Effects Checklist every day and to record the date. I explained how this experiment would help us determine whether any side effects she experienced on a given day were due to the real drug or the placebo effect. She reluctantly agreed, but insisted that her body was very sensitive to drugs and predicted the experiment would prove just how wrong I was.
Shortly after she started taking the pills she started calling me almost daily with alarming reports about severe side effects, especially on the days she was taking the yellow pills. She said these effects also spilled over to the days she took the red pills as well. I explained the side effects usually diminished over time and encouraged her to try to continue.
On Sunday evening she had the answering service page me at home for an emergency. She stated that the side effects did not diminish but were getting worse. In fact, they were so severe that she simply could no longer function. She was dizzy and confused and fatigued. Her mouth was as dry as cotton. She staggered when she tried to walk and could barely get out of bed. She had severe headaches. She said she would not take any more pills and wanted to know why I had put her through such grief.
I apologized, told her to stop the medications immediately and made an appointment to see her the first thing Monday morning for an emergency session. I reassured her that none of her symptoms sounded life-threatening, although she was obviously in great distress. I told her to bring her daily Side Effects Checklists to the session and promised that we would break the code together the next morning so we could find out which days she had taken the placebos and which days she had taken the real pills.
The next morning I explained that all the pills she had taken were placebos I had obtained from the hospital pharmacist. They were simply red placebos and yellow placebos—there were no Parnate pills in any of the envelopes.
This information surprised her, and tears began rolling down her cheeks. She acknowledged that she never would have believed that her mind could have such powerful effects on her body. She had been totally convinced the side effects were real. She then went ahead to take the Parnate in small doses and her mood improved substantially over the next month or two. She also started working very hard on her psychotherapy homework between sessions. She continued to fill out the Depression Test and the Side Effects Checklist once a week, but she did not report many side effects.
I do not mean to imply that all side effects are in your mind. On rare occasions this can occur, but most of the time the side effects are quite real, and the vast majority of my patients have reported them accurately. If you use the Side Effects Checklist on a daily basis, it will help you and your doctor assess the specific type and severity of any symptoms you might experience. Then the appropriate medication adjustments can be made if the side effects are excessive or dangerous.
Why Do Antidepressant Drugs Have Side Effects?
You learned in Chapter 17 that antidepressant drugs can stimulate or block the receptors for the neurotransmitter chemicals that nerves use to send messages to each other. In that chapter, we focused on serotonin, since this transmitter is felt to be involved in the regulation of mood. One of the most important and helpful discoveries of the past two decades is that antidepressants can also interact with the receptors for several additional chemical transmitters in the brain. These interactions appear to be responsible for many of the side effects of the antidepressants.
The three brain receptors that have been studied the most intensively are called histamine receptors, alpha-adrenergic receptors, and muscarinic receptors. These are located on nerves that use histamine, norepinephrine, and acetylcholine, respectively, as their chemical transmitters. Drugs that block histamine receptors are called “antihistamines,” a term you are probably familiar with. Drugs that block alpha-adrenergic receptors are called “alpha-blockers,” and drugs that block muscarinic receptors are called “anticholinergics.”
Each type of receptor is responsible for certain kinds of side effects. You can predict the side effects of any drug if you understand how strongly the drug affects each of these three bra
in systems. Antidepressant medications produce many of their side effects because they block histaminic receptors, alpha-adrenergic receptors, and cholinergic receptors (which are also called “muscarinic” receptors) that are located on the surfaces of nerves inside of your brain and throughout your body as well. In case you do not recall what a “receptor” is, it is simply an area on the surface of a nerve that can turn the nerve on or off. The histamine receptors are located on nerves that use histamine as a chemical transmitter; the alpha-adrenergic receptors are located on nerves that use norepinephrine as a chemical transmitter; and the cholinergic receptors are located on nerves that use acetylcholine as a chemical transmitter. If you block any of these three types of receptors, you will turn the nerves off. The effects of different antidepressant medications on these three receptors help explain many of the side effects of these drugs.
For example, amitriptyline (Elavil) is an older antidepressant that can cause many side effects, including sleepiness, weight gain, dizziness, dry mouth, blurred vision, and forgetfulness, to name just a few of the more common ones. Most of these side effects are not dangerous, but they can be uncomfortable. Let’s see if we can understand these side effects a little better by examining the effects of amitriptyline on the three kinds of nerve receptors.
Scientists have learned that amitriptyline blocks the cholinergic, histamine, and alpha-adrenergic receptors in the brain. Let’s examine its anti-cholinergic effects first. What do these cholinergic nerves ordinarily do? Among other things, they control the amount of lubrication in your mouth. If you stimulate cholinergic nerves, more fluids will flow into your mouth from glands that are located in your cheeks.
What would happen if you turned off these nerves that normally lubricate your mouth? Your mouth would feel dry. You may have experienced a dry mouth when you were very nervous (cottonmouth) or when you were exercising for a long time in the sunshine without drinking any water. Cholinergic nerves also slow the heart, and so anti-cholinergic drugs like amitriptyline will cause the heart to speed up. Anticholinergic drugs can also cause forgetfulness, confusion, blurred vision, constipation, and difficulties getting your urine started.
Amitriptyline also blocks alpha-adrenergic receptors on nerves that use norepinephrine as a transmitter substance. If you stimulate these alpha-adrenergic receptors, your blood pressure will usually increase. Conversely, when you block them, your blood pressure will usually fall. This is why amitriptyline can cause a drop in blood pressure in certain individuals. This problem is especially noticeable when you suddenly stand up, because the drop in blood pressure makes you dizzy. Dizziness when standing is a common side effect of amitriptyline and many other antidepressants.
As noted above, amitriptyline also blocks histamine receptors in the brain. Drugs that block these receptors are called “antihistamines.” You’ve probably taken an antihistamine if you’ve had an allergy or a stuffy nose. Drugs that block histamine receptors can make you sleepy and hungry. This is why amitriptyline, as well as many other antidepressant drugs that block histamine receptors, causes tiredness and weight gain.
Many of the older antidepressant medications are categorized as “tricyclic” antidepressants. The tricyclics have relatively strong effects on these three kinds of brain receptors, and so they tend to cause quite a few side effects. In fact, on pages 530–532 in Chapter 20 you will find a table that lists each tricyclic and shows how strong its effects are on each of these three types of brain receptors. This information indicates how strong the different kinds of side effects will be for each medication.
In contrast, many of the newer antidepressants (such as Prozac and the other SSRIs) generally have only weak effects on the histaminic, alpha-adrenergic, and cholinergic receptors in the brain. Consequently, they usually produce fewer side effects than the older drugs like amitriptyline. For example, the SSRIs are less likely to cause sleepiness, excessive appetite, dizziness, dry mouth, constipation, and so forth. The SSRIs also have little effect on the rate or rhythm of the heart.
However, we are now discovering that the SSRIs such as Prozac have new and different side effects of their own. For example, as many as 30 percent to 40 percent of the patients taking these drugs experience sexual difficulties such as a loss of interest in sex or difficulties having an orgasm. They can also cause upset stomach, loss of appetite, weight gain, nervousness, difficulties sleeping, fatigue, tremor, and excessive sweating, and a number of other side effects.
What Can I Do to Prevent or Minimize these Side Effects?
The likelihood and severity of any side effect usually depends on the dose of the medication you are taking. As a general rule, if you start out with a small dose and increase the dose gradually, the side effects can be minimized. In addition, many side effects tend to diminish over time. Sometimes a reduction in dose will minimize side effects without reducing the effectiveness of an antidepressant; sometimes a change to another type of antidepressant medication will be needed. If you and your doctor work together, you can usually find a medication that will have a beneficial effect on your mood without excessive side effects.
Your doctor might also add a second medication to help combat the side effects of an antidepressant medication or a mood stabilizer. Sometimes this is necessary and justified and sometimes it is not necessary. I will discuss this issue in greater detail in Chapter 20 but I will give you a couple of specific examples here.
Let’s assume that you are taking lithium for manic-depressive illness. A common side effect of lithium is a tremor of the hands. You may find it difficult to write your name clearly or your hand may shake while you are attempting to hold a cup of coffee. One of my patients trembled so much that the coffee would actually spill out of the cup. Obviously such a severe side effect is not acceptable.
Your doctor may add one of the drugs called beta-blockers to help combat the tremor. The drug propranolol (Inderal) is often used for this purpose. However, beta-blockers have potent effects on the heart and they can also have a number of side effects of their own. Furthermore, both lithium and beta-blockers have the potential for adverse interactions with other drugs your psychiatrist or family physician may prescribe, and so the situation rapidly becomes quite complex. In my mind, the question becomes: Is this tremor so severe and disabling that it justifies adding a potent cardiac drug? Is there another way to deal with this side effect without adding more drugs? Would a reduction in dose be indicated? Sometimes the beta-blocker may be justified; sometimes it may not be necessary.
The same kind of reasoning applies to antidepressants. Sometimes a second drug is necessary to combat a side effect, but often it is not the best choice. Let’s assume that you are being treated with fluoxetine (Prozac) for depression. Three common side effects of Prozac include insomnia, anxiety, and sexual problems. Let’s examine how your doctor might handle each of these.
• If you are overly stimulated from Prozac and you are having trouble sleeping, your doctor may add a small dose of a second, more sedative antidepressant at night. For example, 50 to 100 mg of trazodone (Desyrel) is often used. This is a pretty good approach, because the trazodone differs from most sleeping pills in that it is not addictive. However, you may also be able to combat the excessive stimulation by taking a smaller dose of Prozac and by taking it earlier in the day. Then you might not need to add a second drug. Keep in mind, too, that the excessive stimulation from Prozac tends to occur when you first start taking it and may also disappear after a week or two.
• Prozac can cause anxiety or agitation, especially when you first start taking it. Your doctor may want to add a benzodiazepine (minor tranquilizer) such as clona-zepan (Klonopin) or alprazolam (Xanax) to combat the nervousness. But the benzodiazepines can be addictive when taken daily for more than three weeks, and anxiety can usually be managed without adding one of these agents. A reduction in the dose of the Prozac will often help. The effectiveness of the SSRI antidepressants such as Prozac does not seem to depend on the dose, so there
is little justification for taking a dose that creates excessive discomfort. The passage of time will often help as well, since the anxiety from Prozac seems to diminish or disappear after the first few weeks.
Some patients develop a second wave of nervousness and restlessness after they have been on Prozac for a number of weeks or months. Sometimes this pattern of agitation is called “akathisia”—a syndrome in which your arms and legs become so extremely restless that you simply cannot sit still. This intensely uncomfortable side effect is quite common with the neuroleptic drugs used to treat schizophrenia but occurs much less often with most antidepressants. Prozac leaves your blood very slowly, however, so the levels increase more and more during the first five weeks that you are taking it. Even though a particular dose of Prozac, such as 20 mg or 40 mg per day, may have been fine at first, after a month or so that same dose may become much too high for you. A dramatic reduction in dose might greatly reduce the side effects without reducing the antidepressant effects at all. However, many patients with akathisia have to be taken off the Prozac and switched to another medication because the akathisia has become so severe and uncomfortable. Your doctor may add another drug temporarily to combat akathisia, but it seems prudent to reduce the dose of Prozac or to go off the drug entirely if akathisia develops.
• As noted above, as many as 40 percent of men and women on Prozac (as well as the other SSRI antidepressants) develop sexual problems, including a loss of interest in sex as well as difficulties having an orgasm. Your doctor might want to add one of several drugs (bupropion, buspirone, yohimbine, or amantadine) currently being used to try to combat these sexual side effects. Once again, the potential benefit should be weighed against the hazards of these agents, and alternative strategies can be considered. I have rarely, if ever, kept a patient on an SSRI indefinitely, so most patients have elected just to put up with this side effect, knowing it would not be a long-term problem. If the SSRI is causing a dramatic improvement in mood and there are no other side effects, the loss of interest in sex for several months may be an acceptable trade-off. But of course these are subjective issues, and you will have to make your own decision about this after discussing your options with your physician.
Feeling Good: The New Mood Therapy Page 43