Depression is commonly treated with antidepressant medications. Antidepressants work to balance some of the natural chemicals in our brains. These chemicals are called neurotransmitters, and they affect our mood and emotional responses. Antidepressants work on neurotransmitters such as serotonin, norepinephrine, and dopamine.

The most popular types of antidepressants are called selective serotonin reuptake inhibitors (SSRIs). These include:

• Fluoxetine (Prozac)
• Citalopram (Celexa)
• Sertraline (Zoloft)
• Paroxetine (Paxil)
• Escitalopram (Lexapro).

Other types of antidepressants are serotonin and norepinephrine reuptake inhibitors (SNRIs). SNRIs are similar to SSRIs and include venlafaxine (Effexor) and duloxetine (Cymbalta). Another antidepressant that is commonly used is bupropion (Wellbutrin). Bupropion, which works on the neurotransmitter dopamine, is unique in that it does not fit into any specific drug type.

SSRIs and SNRIs are popular because they do not cause as many side effects as older classes of antidepressants. Older antidepressant medications include tricyclics, tetracyclics, and monoamine oxidase inhibitors (MAOIs). For some people, tricyclics, tetracyclics, or MAOIs may be the best medications.

What are the side effects?

Antidepressants may cause mild side effects that usually do not last long. Any unusual reactions or side effects should be reported to a doctor immediately.

• Headache, which usually goes away within a few days.
• Nausea (feeling sick to your stomach), which usually goes away within a few days.
• Sleeplessness or drowsiness, which may happen during the first few weeks but then goes away. Sometimes the medication dose needs to be reduced or the time of day it is taken needs to be adjusted to help lessen these side effects.
• Agitation (feeling jittery).
• Sexual problems, which can affect both men and women and may include reduced sex drive, and problems having and enjoying sex.

• Dry mouth.
• Constipation.
• Bladder problems. It may be hard to empty the bladder, or the urine stream may not be as strong as usual. Older men with enlarged prostate conditions may be more affected.
• Sexual problems, which can affect both men and women and may include reduced sex drive, and problems having and enjoying sex.
• Blurred vision, which usually goes away quickly.
• Drowsiness. Usually, antidepressants that make you drowsy are taken at bedtime.

People taking MAOIs need to be careful about the foods they eat and the medicines they take. Foods and medicines that contain high levels of a chemical called tyramine are dangerous for people taking MAOIs. Tyramine is found in some cheeses, wines, and pickles. The chemical is also in some medications, including decongestants and over-the-counter cold medicine.

Mixing MAOIs and tyramine can cause a sharp increase in blood pressure, which can lead to stroke. People taking MAOIs should ask their doctors for a complete list of foods, medicines, and other substances to avoid. An MAOI skin patch has recently been developed and may help reduce some of these risks. A doctor can help a person figure out if a patch or a pill will work for him or her.

How should antidepressants be taken?

People taking antidepressants need to follow their doctors' directions. The medication should be taken in the right dose for the right amount of time. It can take three or four weeks until the medicine takes effect. Some people take the medications for a short time, and some people take them for much longer periods. People with long-term or severe depression may need to take medication for a long time.

Once a person is taking antidepressants, it is important not to stop taking them without the help of a doctor. Sometimes people taking antidepressants feel better and stop taking the medication too soon, and the depression may return. When it is time to stop the medication, the doctor will help the person slowly and safely decrease the dose. It's important to give the body time to adjust to the change. People don't get addicted, or "hooked," on the medications, but stopping them abruptly can cause withdrawal symptoms.

If a medication does not work, it is helpful to be open to trying another one. A study funded by NIMH found that if a person with difficult-to-treat depression did not get better with a first medication, chances of getting better increased when the person tried a new one or added a second medication to his or her treatment. The study was called STAR*D (Sequenced Treatment Alternatives to Relieve Depression).^2,3

Are herbal medicines used to treat depression?

The herbal medicine St. John's wort has been used for centuries in many folk and herbal remedies. Today in Europe, it is used widely to treat mild-to-moderate depression. In the United States, it is one of the top-selling botanical products.

The National Institutes of Health conducted a clinical trial to determine the effectiveness of treating adults who have major depression with St. Johns wort. The study included 340 people diagnosed with major depression. One-third of the people took the herbal medicine, one-third took an SSRI, and one-third took a placebo, or "sugar pill." The people did not know what they were taking. The study found that St. John's wort was no more effective than the placebo in treating major depression.⁴ A study currently in progress is looking at the effectiveness of St. John's wort for treating mild or minor depression.

Other research has shown that St. John's wort can dangerously interact with other medications, including those used to control HIV. On February 10, 2000, the FDA issued a Public Health Advisory letter stating that the herb appears to interfere with certain medications used to treat heart disease, depression, seizures, certain cancers, and organ transplant rejection. Also, St. Johns wort may interfere with oral contraceptives.

Because St. John's wort may not mix well with other medications, people should always talk with their doctors before taking it or any herbal supplement.

FDA warning on antidepressants

Antidepressants are safe and popular, but some studies have suggested that they may have unintentional effects, especially in young people. In 2004, the FDA looked at published and unpublished data on trials of antidepressants that involved nearly 4,400 children and adolescents. They found that 4 percent of those taking antidepressants thought about or tried suicide (although no suicides occurred), compared to 2 percent of those receiving placebos (sugar pill).

In 2005, the FDA decided to adopt a "black box" warning label—the most serious type of warning—on all antidepressant medications. The warning says there is an increased risk of suicidal thinking or attempts in children and adolescents taking antidepressants. In 2007, the FDA proposed that makers of all antidepressant medications extend the warning to include young adults up through age 24.

The warning also says that patients of all ages taking antidepressants should be watched closely, especially during the first few weeks of treatment. Possible side effects to look for are depression that gets worse, suicidal thinking or behavior, or any unusual changes in behavior such as trouble sleeping, agitation, or withdrawal from normal social situations. Families and caregivers should report any changes to the doctor. To find the latest information visit the FDA website.

Results of a comprehensive review of pediatric trials conducted between 1988 and 2006 suggested that the benefits of antidepressant medications likely outweigh their risks to children and adolescents with major depression and anxiety disorders.⁵ The study was funded in part by NIMH.

Finally, the FDA has warned that combining the newer SSRI or SNRI antidepressants with one of the commonly-used "triptan" medications used to treat migraine headaches could cause a life-threatening illness called "serotonin syndrome." A person with serotonin syndrome may be agitated, have hallucinations (see or hear things that are not real), have a high temperature, or have unusual blood pressure changes. Serotonin syndrome is usually associated with the older antidepressants called MAOIs, but it can happen with the newer antidepressants as well, if they are mixed with the wrong medications.