Antidepressants: Wellbutrin, Effexor, Remeron, and Desyrel

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Additional Antidepressants
For Depression

What about antidepressants like Wellbutrin, Effexor, Cymbalta, Remeron, and Desyrel that don't fit into the standard drug type classifications? This article can answer some of your questions about them.

"When I was depressed, it was like having a tight metal band around my head all the time. I felt like my cognitive processes couldn't run with the energy they should have. When I took Wellbutrin and my depression lifted, the band loosened and the relief was incredible."

-- Jim, 42

Jim was the son of two alcoholics, a brilliant but erratic man who blazed through his adolescence and early adulthood and crashed into a fog of depression in medical school. For the next 10 years, he was haunted by intermittent episodes of depression. But it was his inability to function at work that Jim, a drug company executive, found most troubling.

"The problems my depression was causing me at work were particularly devastating," he recalls today. "I was trying to build my ego late in life, which is fairly common among children of alcoholics. And my depression was getting in the way of my healthy functioning."

In a vain attempt at self-medication, Jim began using cocaine regularly. When he was finally given a prescription for Wellbutrin, he had given up hope that he would ever regain his ability to think clearly.

Within a week, he began to notice an effect. Within five or six weeks, his depression was gone. "Being able to focus again on work, instead of on myself and my problems, was initially the most uplifting effect," he recalls. Wellbutrin also helped him overcome his cocaine addiction.

Bupropion (Wellbutrin), trazodone (Desyrel), venlafaxine (Effexor), duloxetine (Cymbalta) and mirtazapine (Remeron) are a group of structurally unrelated antidepressants that don't fit into any of the established antidepressant drug classes of MAOIs, tricyclics, or SSRIs.

These five are among a group of drugs that scientists have discovered as a result of fiddling with the biochemistry of antidepressants, looking for the perfect medication that's safe, nontoxic, and effective. Although all three are very effective antidepressants, each one affects a different neurotransmitter system: Wellbutrin affects dopamine, Desyrel affects serotonin, and Effexor and Cymbalta affect norepinephrine, serotonin, and dopamine, while Remeron stimulates norepinephrine and serotonin release as it blocks certain receptors.

Pros and Cons

Wellbutrin, Effexor, Cymbalta, Desyrel, and Remeron appear to cause fewer serious side effects than MAO inhibitors or tricyclics. But because these drugs can cause a few unusual problems in some people, chances are your psychiatrist will be far more likely to choose an SSRI like Prozac or Zoloft at first.

The most common side effects shared by Wellbutrin, Effexor, Cymbalta, and Desyrel include agitation, dry mouth, insomnia, headache, nausea and vomiting, constipation, and tremors.

But perhaps the most troubling problem with the newer drugs is that no one is sure just what their long-term effects might be. There are some new, troubling reports that Effexor may cause tardive dyskinesia, a movement disorder that may be permanent, involving writhing, wormlike movements of the body, lips, and tongue.

But many chronically depressed people say they don't care. They're willing to pay the price of future uncertainty to buy freedom from depression today.

"There are risks to these drugs," says Joan, whose training as a nurse makes her more aware than most of the possible hazards. "They just don't know what they do in the body. But after this many years of being depressed, it's worth the risk to me. I've spent half my life in hell, so taking a risk with antidepressants is well worth the effort. As more years have gone by, I see the years I was depressed as wasted. I don't want to waste any more."

Wellbutrin

The good news about Wellbutrin is that you probably won't have sexual problems, you won't gain weight (you may even lose a few pounds!), and you won't have a lot of annoying minor side effects. The bad news is that -- especially if you've had a head injury or you have epilepsy -- there's a higher risk of seizures.

"Wellbutrin is usually my second-choice antidepressant," says psychiatrist Andy Myerson. "I've had remarkable success with it, but many people are scared by the potential for seizures. It's tricky."

Because Wellbutrin blocks dopamine, this drug also can rarely produce movement disorders and changes in the endocrine system.

As mentioned above, the biggest problem associated with Wellbutrin is the fact that psychiatrists are nervous about a risk of seizure four times higher than with other antidepressants. Overdosing is a particular danger, since the chance of a seizure increases almost tenfold at twice the normal daily dose of 300 milligrams. Your biggest chance of developing a seizure appears to be if you've had a prior serious head injury or prior seizures, brain or spinal-cord tumors, if you take anti-seizure medication, or if you suddenly hike your dosage. You can lower the risk if you never abruptly increase your dosage, don't take more than 450 milligrams a day, and limit any single dose to no more than 150 milligrams.

Some patients find that Wellbutrin's action on the central nervous system can produce unpleasant hypersensitivity. "When I took Wellbutrin, I spent a lot of time on my sofa with the blanket over my head," comments Eleanor, 39, a Colorado stockbroker. "I felt oversensitized all over my body. I just felt weird."

But others have found benefit with the drug. Since Wellbutrin is not sedating, you feel some effect right away because you don't have to work your way through the haze of sedation produced by the tricyclics and MAOIs.

"I took tricyclics for about four days. I was so sleepy, my face fell into my food at Thanksgiving," recalls Jim. "But with Wellbutrin, I was able to work again, and that gave me hope. Hope is something you don't have when you're depressed."

One of the most demoralizing problems with almost all antidepressants is their negative effect on sexual function, such as decreased libido, erection problems, and impotence. Wellbutrin's boost to the libido can come as a welcome relief to many people; indeed, some patients can find Wellbutrin too sexually stimulating.

"I was thinking about sex all the time," complains Hilary, 39, who was given Wellbutrin when Zoloft did not relieve her depression. "I spent all my time in bed."

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While there have been no reports that Wellbutrin caused liver damage, animal studies have revealed a variety of liver problems with this drug. And don't be surprised if you feel restless; some number of people taking Wellbutrin report some amount of agitation, anxiety, and insomnia, especially at the beginning of treatment. Some people have needed to be treated with sedatives or hypnotic drugs to ease the anxiety. A new formulation of Wellbutrin, Wellbutrin SR, has a more favorable side effect profile than the original version.

"Psychiatrists end up getting the treatment failures from other people," says Dr. Myerson. "Almost everything causes sexual problems, and with Wellbutrin there is less of that. But when people don't like Wellbutrin, they really hate it."

Very rarely, patients treated with either Wellbutrin or Desyrel develop serious mental symptoms including delusions, hallucinations, psychotic episodes, confusion, paranoia, hostility, disorientation, memory problems, or nightmares, but studies have not shown what the exact percentage risk may be. In some cases, the symptoms decreased when the dosage was decreased or withdrawn.

Desyrel

Then there's Desyrel. Unlike antidepressants such as Prozac that may keep you pacing the floor at night, Desyrel can have you sleeping like a baby. On the down side, on rare occasions Desyrel may cause a nasty side effect called priapism, a painful erection of the penis without sexual arousal. Priapism occurs when blood doesn't drain from the penis's spongy tissue, keeping it erect. Urgent treatment is needed because of the risk of permanent damage to the penis. Other patients experience permanent impairment of erection or impotence.

Desyrel has also been linked to some heart problems, and birth defects in animals.

Some of the side effects of these drugs may actually work for you. For example, because of Desyrel's sedative qualities, it's often added to other drugs like Prozac, if insomnia becomes a problem.

"Before taking antidepressants, I was having a lot of trouble sleeping because of my depression," notes Sarah, 42. "After a few weeks on Prozac, I still wasn't sleeping, so my psychiatrist added Desyrel. I take it right before I go to sleep, and I've been sleeping again for the first time in years."

Remeron (Mirtazapine)

Approved by the FDA in July 1996, Remeron offers another approach to the treatment of depression and is often helpful for people having trouble with sleep and anxiety. The first of a new class of drugs, Remeron does not broadly block the reuptake of norepinephrine or serotonin like other SSRIs. Instead, Remeron stimulates the release of norepinephrine and serotonin, while blocking certain receptors that have been linked with lowered sex drive, nausea, nervousness, headache, insomnia, and diarrhea. As a result, Remeron does not usually lead to any of these side effects. Many people have been particularly troubled by the loss of sexual interest or ability with SSRIs; but, in United States studies, a lowered sex drive occurred in only one percent of patients receiving Remeron.

This doesn't mean that Remeron is free of side effects. For some people, fatigue, weight gain, increased appetite, and dizziness can be troublesome. Still, the dropout rate is low; in U.S. studies only about 16 percent of patients stopped taking the drug because of unpleasant side effects.

"I didn't think I'd ever feel this good again," said Joe, a 43-year-old severely depressed teacher who had tried several other antidepressants without success. "I even got my sex life back!"

Caution: Anyone who is taking Remeron who develops an infection and has a low white-blood-cell count should stop the drug. It should be used with caution in those with liver or kidney problems. Older patients (especially older men) may find it takes longer for the drug to clear their system. As with SSRIs, you should not take Remeron at the same time as a monoamine oxidase inhibitor (MAOI) or use it within two weeks of stopping or starting MAOI treatment.

Effexor

If you had your heart set on taking Prozac and were disappointed when nothing happened, there's a drug that seems to work especially well for the up to 40 percent who don't respond to serotonin-related antidepressants. It's called Effexor, approved in 1994 by the FDA. Because Effexor is structurally unlike SSRIs, people who don't respond to Prozac, Zoloft, or one of the tricyclics often do respond to this antidepressant. It's so new, however, that doctors don't know a lot about how this drug will act on a long-term basis. As mentioned above, there are some concerns that this drug may cause tardive dyskinesia -- usually after long-term use, although there have been some cases appearing after only one dose.

Tricia, 39, is a Boston nurse who ended up taking Effexor for a lifelong depression after trying every known tricyclic. "The first effects of Effexor were visual," she recalls. "I felt as if there was a cool breeze blowing behind my eyes. Colors were sharper, and all my senses perked up. I feel the way I imagine normal people feel, without struggling through the haze of depression. It clarified things."

The feeling of clarity was especially important to Tricia, who was terrified that the muted experience of her depression would lead her to make mistakes at work. "I was constantly afraid I would kill someone," she recalls. As a result, she became hypervigilant at work, putting so much energy into her job that at the end of the day she was totally exhausted.

"Before Effexor, every morning I would usually have a few suicidal thoughts before I left for work in the morning. Now I'm afraid that this (normal feeling) will be taken away."

Before Taking These Drugs

Just as with other antidepressants, you've got to be sure to tell your doctor if you've ever had allergies to any antidepressants, foods, preservatives, or dyes, and if you have suffered from manic depression, convulsions, or seizures. Be sure to report liver disease, since this condition may raise blood levels of any antidepressant, which can in-crease the risk of side effects. If you have any type of seizure disorder, recent head injury, brain or spinal-cord tumor, bulimia, or anorexia nervosa, you shouldn't take Wellbutrin either, since all of these problems have been associated with a higher risk for seizures. And if you've had a recent heart attack, you may not be able to take antidepressant medication.

Additional Tests

If you're taking Wellbutrin, talk to your doctor about the possible need for follow-up medical exams or studies to check kidney and liver function or blood levels of the drug.

When taking Desyrel, you may need to take complete blood-cell-count tests, since this drug can reduce your white-blood-cell count. (White blood cells are an important part of your body's immune system, and low levels could be a problem if you develop an infection, sore throat, or fever.) Because of the link between Desyrel and some heart problems, your doctor may ask you to have blood-pressure readings and electrocardiograms.

How to Take These Drugs

To lessen stomach upset, it's a good idea to take any of these three drugs with meals unless your doctor has specifically asked you to take your medication on an empty stomach.

When taking Wellbutrin, you should equally divide your medication into three or four doses a day to minimize the risk of seizure. Never drink alcohol while taking Wellbutrin, since this also may increase the risk of seizure.

If you get too sleepy or dizzy with Desyrel, ask your doctor if you can take a larger portion of your total daily dose at bedtime, dividing the rest into two or three smaller doses during the day.

Possible Drug Interactions

As with all antidepressants, you should talk to your doctor before taking any other drugs (even nonprescription medications).

Taking Wellbutrin with a tricyclic antidepressant may increase the risk of seizure. Taking Wellbutrin with an MAO inhibitor, or within two weeks of taking an MAO inhibitor, will increase the chance of side effects. At least two weeks should pass between stopping one medication and taking another.

Overdose

An overdose is less of a problem with the newer antidepressants. That's another reason why doctors like to give these newer drugs to suicidal patients -- they're less likely to be able to take a fatal overdose. If you overdose on Wellbutrin, you'll probably recover, although you might experience seizures or hallucinations or lose consciousness. Still, there have been cases of heart failure and fatalities from Wellbutrin overdoses.

Pregnancy and Breast-Feeding

If you want to get pregnant while you're on an antidepressant, you're going to have to weigh the risks to your baby against the risks to you if you don't take the drug. As with most antidepressants, what we know about their activity in pregnant women is mostly obtained from animal studies, not from large-scale studies in humans.

Your best choice might be Wellbutrin, which hasn't caused birth defects or other development problems in animal studies even in doses up to 45 times the human daily dose. The effect of Wellbutrin on labor and delivery in humans isn't known, however.

Desyrel seems a little more risky; animal studies with this drug have revealed fetal deaths and birth defects. As a result, use of Desyrel is not recommended during the first three months of pregnancy.

You and your doctor should weigh the potential risks to the fetus and to you before you decide whether or not to take antidepressants during pregnancy.

There's always a potential for adverse reactions in nursing infants (especially with Wellbutrin). If you're a new mom, you need to weigh the risks to you of not taking medication against the potential harm to your baby.

Use with the Elderly

If you're over age 60, you're more likely to be sensitive to all of the antidepressants. This means your depression will probably respond to lower doses of medication. It also means you are at higher risk for developing side effects.

Some antidepressants may be a better choice than others, of course. For example, studies with Wellbutrin in a limited number of patients over age 60 haven't found any problems caused by the drug.

Additional Antidepressants For Depression