All About Antidepressants

On October 15, 2004, the FDA has concluded that antidepressant medications increase the risk of suicidal thinking and behavior in children and adolescents with depression and other psychiatric disorders. If you have questions or concerns, discuss them wit All About Antidepressants
All About Antidepressants

“When I was depressed, I was always overwhelmed. It took me so long to do any normal job, just brushing my teeth took forever. I felt doomed all the time. After I took Effexor, I felt as if this terrible weight, this slowing down, had been lifted.”

—Barbara, 49

There’s no best way to treat all types of people and depression. In fact, more and more psychiatrists are coming to the conclusion that major recurrent depression is a chronic disease that may require lifetime medication. And while studies suggest that a combination of psychotherapy and antidepressants is the most effective treatment for depression, for some chronically depressed people talk therapy just doesn’t help—and it can foster deep feelings of resentment.

“I spent years in group therapy,” says Jan, a 39-year-old Boston nurse. “I spent decades talking to experts. I came to realize that I’d put all the honesty a person could muster into my therapy, and I still wasn’t any better. Something always felt physically wrong. I always felt I had a biochemical twist in me that had to be responsible. If I could only tell the hours, years, the money I poured into getting well!”

Finally, a psychiatrist at McLean Hospital in Belmont, Massachusetts, diagnosed Jan as depressed and recommended antidepressants. “Everyone needs a friend,” Jan says, “but I think that’s where psychotherapy ends—at least for severe depression.”

Today there are more than 20 antidepressants on the market, many with fewer side effects than those prescribed a decade ago. Some experts are worried that people will see antidepressants as a quick fix for profoundly complex problems without trying to correct these underlying problems through psychotherapy. Others insist that the drugs simply restore a person’s emotional equilibrium, allowing problems to be ironed out without the burden of crushing sadness.

In fact, studies show that combining antidepressants with therapy provides the best chance of treating depression.
Iproniazid: The First Antidepressant

The first of the modern antidepressants—iproniazid—was developed in the early 1950s not to treat depression but to ease the symptoms of tuberculosis. At the time, iproniazid was unmatched as a weapon in the ongoing fight against this deadly respiratory illness, decreasing the number of tubercule bacilli and suppressing their proliferation. But while it was designed to treat tuberculosis, as a side benefit iproniazid also seemed to be a sort of “happy drug,” pepping up patients, improving their appetites, and restoring their feelings of well-being.

The drug’s positive emotional effects immediately attracted the attention of physicians and depression researchers. The only chemical treatment for depression at that time was opium, a highly addictive substance. The possibility of a more effective—and nonaddictive—drug that could alleviate mood disorders was an attractive thought. Up to that time, some drugs could alleviate one or two symptoms of depression, but none could completely eradicate the condition.

Psychiatrists began to consider using iproniazid as a potential antidepressant just when its manufacturers were getting ready to stop production in the wake of newer, even better-acting antitubercular drugs. With the publication of research in 1957 illustrating the success of iproniazid in the treatment of depression, a flurry of prescriptions were written almost immediately. Within that year, physicians had prescribed it for more than 400,000 depressed patients.

Unfortunately, 127 of them developed jaundice. Although historians believe the jaundice was related to viral hepatitis that was epidemic at that time and not to the iproniazid, its manufacturer withdrew the drug because of adverse publicity.

At about the same time, psychiatrist Roland Kuhn began experimenting with imipramine (Tofranil), the first of the cyclic antidepressants. Imipramine was released in 1958, and amitriptyline (Elavil, Endep, and Amitid) was released soon afterward. Eventually, six other tricyclics were introduced in this country.

After reviewing more than 400 clinical studies of antidepressants, a federal panel of researchers concluded that no one antidepressant was clearly more effective than another, and no one drug successfully treated all cases of depression. Only about half the people find relief with the first antidepressant they are prescribed. This panel also found that psychotherapy together with antidepressants is slightly more effective, helping people understand their problems and relieving stress that may worsen symptoms.
How Antidepressants Work

Although scientists don’t know for sure, antidepressants appear to correct a chemical imbalance or dysfunction in the brains of depressed people. An antidepressant boosts the level of neurotransmitters important in fighting depression. Each of the major classes of antidepressants—monoamine oxidase inhibitors (MAOIs), tricyclics, and serotonin inhibitors—affects different neurotransmitter systems in a different way.

Tricyclic antidepressants are a class of traditional drugs that treat depression by boosting the level of several different neurotransmitters (norepinephrine, epinephrine, serotonin, and dopamine) by blocking their reabsorption. MAOIs destroy enzymes responsible for burning up neurotransmitters, thereby boosting the neurotransmitter levels. In general, MAOIs are used to treat those who don’t respond to tricyclics. Some of the newest antidepressants (including Prozac) interfere with the reabsorption of one specific neurotransmitter (serotonin).
Choosing an Antidepressant

Because it seems as if everyone is talking about Prozac, you may be surprised if your doctor doesn’t prescribe it right away for your depression. Actually, many doctors feel more comfortable with one of the older antidepressants (tricyclics or MAOIs) because for more than 35 years they’ve had success prescribing these drugs.

While these drugs do have more side effects than Prozac and other new drugs, many patients can tolerate these problems. More cautious, conservative physicians may choose an “old reliable” despite miraculous claims for the new medications because of worries about unknown long-term effects. If your doctor gives you one of these older drugs and you can’t tolerate the side effects or it doesn’t help your depression, then he or she may feel more justified in trying one of the newer drugs.

The complex array of brain chemicals and processes that influence depression tends to differ from one patient to the next; because there’s no foolproof way to identify what’s causing your depression, prescribing antidepressants may be a trial-and-error process until the right one is found.

“My psychiatrist started me out on Zoloft,” recalls Linda, 38. “After six weeks, it had done nothing for me, so he switched me to Wellbutrin. I took that for two weeks, but I became oversensitive. So then I was on Prozac for three days, but it made me manic. Then he tried Paxil and added lithium to keep me from getting manic. That’s what I’ve been on for over a year, and it’s been great.”

Linda’s case illustrates the fact that for many people, the first antidepressant is often not the right antidepressant. In fact, only a little more than half of all patients who are given antidepressants find relief with their first prescription. No one is quite sure how or why antidepressants work, and no one can predict who will respond to which drug.

“It’s a crapshoot,” says Dr. Myerson. “We don’t have good guidelines about which person will do well on which drug. So we just have to wade through, try different drugs, adjust dosages, and add drugs to drugs. You can have two patients who look identical, but one will respond well to Zoloft and one to Prozac. And we have no idea why.”

The best a physician can do is to look at a person’s symptoms and try to match those symptoms with an antidepressant. Too often, physicians don’t fully explain the side effects and problems a patient may encounter. It’s vital to understand the benefits and risks of each antidepressant as you and your physician search for the best treatment.

“Many of my patients don’t like to confess that they are still depressed,” one psychiatrist noted. “They feel as if they’re letting me down somehow.”

There is no one miracle antidepressant that works better than any other, all the time, for everybody. Because depression itself is a complex disease with many causes, doctors must choose from a wide range of antidepressants that work on different brain systems and affect different processes.

When your doctor prescribes an antidepressant, be sure you understand:

* Which drugs might interact with your antidepressant or cause a toxic reaction.
* What do you do if you miss one dose—or several doses.
* What is the best time of day to take your medication, and how should you take it (on an empty stomach? with food?).
* What side effects should you expect and how should you manage them.
* How long it will take for the drug to work and how you will know when it’s working.
* Which side effects are serious enough that you need to contact the doctor immediately.

Combining Drugs

If the first drug fails and your physician has determined that the drug was taken in the right dosage for the correct length of time, he or she may try a different drug. If this second drug also fails, your physician may try combining several different drugs.

When Sara first sought help for her depression, her doctor prescribed an antidepressant and referred her to group therapy. But the first antidepressant didn’t seem to do much good—it made her jittery and worsened her sleep problems. When a dosage adjustment didn’t improve her symptoms, her psychiatrist switched her to another drug. Sara tried three drugs before finally responding to Zoloft and desipramine, which alleviated her crushing sadness within a few weeks without any other side effects.

Recently, a few psychiatrists—like Sara’s doctor—have found that adding desipramine to one of the newer SSRIs such as Prozac or Zoloft seems to work quite well. The dose of each drug is less than would normally be required, so side effects are minimized. A few other drugs, such as thyroid hormone, lithium buspirone (BuSpar), or Ritalin are sometimes added to an antidepressant to boost the drug’s effectiveness. While the use of stimulants such as Dexedrine or Ritalin is controversial because of the risk of abuse, adding these drugs to an antidepressant has been successful in alleviating some patients’ depression.

If you become psychotically depressed with hallucinations or delusions, your doctor may need to add antipsychotic drugs such as haloperidol (Haldol), risperidone (Risperdal), olanzapine (Zyprexa), or quetiapine (Seroquel) to your antidepressant. Electroconvulsive therapy (ECT) may also be helpful.

Drug combinations can be risky, though, since the more drugs that are given at once, the greater the chance of side effects and drug interactions (such as the dangerous combination of stimulants with MAOIs or certain cyclic antidepressants).
How Long Should You Take Antidepressants?

Length of treatment is becoming controversial. While many people take antidepressants for at least six months to a year, more and more doctors have been suggesting that recurrent depression may be chronic. If you’ve had more than two episodes of depression, some doctors believe you’ll probably need to be on antidepressants for the rest of your life.

On the other hand, it’s important not to stop taking antidepressants too soon. Research shows that 70 percent of patients become depressed again if they stop taking their antidepressants too early—five weeks or less beyond the point when their symptoms stop. The relapse rate falls to only 14 percent among those who keep taking their antidepressant at least five months after their symptoms abated. Other studies have also found that the longer the patient is on the antidepressant, the less likely is the chance of getting depressed again.

For this reason, many doctors prescribe antidepressants for six months to a year following the end of a depressive episode, gradually tapering off the dosage over several weeks. Unlike opiates, antidepressants aren’t addictive, and people taking them will not develop a craving once they are stopped. However, physicians recommend patients gradually taper off the medication to avoid restlessness, anxiety, and other unpleasant physical feelings. This also allows for an opportunity to carefully assess the patient’s current need for antidepressant medication.
Side Effects

Side effects from antidepressants generally fall into three categories: sedation; dry mouth, blurry vision, constipation, urinary problems, increased heart rate, and memory problems; and dizziness on standing up (orthostatic hypotension). Drugs that block norepinephrine uptake can produce rapid heartbeat, tremor, and sexual problems. Those that interfere with dopamine (such as Effexor and Asendin) may produce movement disorders and endocrine system changes. Blocking serotonin may create stomach problems, insomnia, and anxiety.

Those that work on the other side of the synapse, blocking receptors that pick up neurotransmitters, have other side effects depending on which receptors are affected. Blocking histamine H1 receptors produces weight gain and sedation; muscarinic receptor blocks cause dry mouth, constipation, blurry vision, and memory problems.

This is why a tricyclic such as amitriptyline (Elavil) causes so many side effects—it blocks the absorption of both norepinephrine and serotonin, plus four different receptors (alpha1, Dopamine D2, histamine H1, and muscarine).

Each drug has a profile of its own particular side effects. Tricyclics often cause dry mouth, constipation, sedation, nervousness, weight gain, and diminished sex drive. MAOIs interact with certain foods and other medications to produce potentially fatal high blood pressure. Newer antidepressants like the SSRIs (such as Prozac, Celexa, Luvox, Paxil, and Zoloft) produce fewer side effects than MAOIs or tricyclics because they affect fewer brain pathways, but nausea and headache may occur.

Although a drug is characterized by certain side effects, that doesn’t mean you’ll necessarily experience any of them; if you do have persistent side effects, you can switch to a drug with a different side-effect profile. Usually, side effects will disappear or diminish in a week or two. In addition, many antidepressants can be taken before bed so the side effects will occur while you sleep. If a bedtime dose makes you too sleepy the next morning, a dose at dinnertime may be a better idea. A physician can work with your schedule to find the dosage timetable that works best for you.

Many antidepressants lower sex drive; they might cause impotence or interfere in achieving orgasm. These side effects can be eliminated by adding another drug or changing the antidepressant. In most cases, where depression has decreased libido, antidepressants will restore it.

You’ve just been given a general overview of antidepressants—what they are and how they can help. This book will cover each class of antidepressant, comparing and contrasting them with SSRIs and explaining the details of each one.

Learn about the selective serotonin reuptake inhibitors (SSRIs) like Prozac, the newest class of antidepressants.

Copyright © 2001 by Carol Turkington and Eliot F. Kaplan, MD. All rights reserved. From “Making the Antidepressant Decision”, by arrangement with Contemporary Books, The McGraw-Hill Companies.
Copyright © 2001 by Carol Turkington and Eliot F. Kaplan, MD. All rights reserved. From “Making the Antidepressant Decision”, by arrangement with Contemporary Books, The McGraw-Hill Companies.

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