Antidepressants work to normalize naturally occurring brain chemicals called neurotransmitters, notably serotonin and norepinephrine. Other antidepressants work on the neurotransmitter dopamine. Scientists studying depression have found that these particular chemicals are involved in regulating mood, but they are unsure of the exact ways in which they work.

The newest and most popular types of antidepressant medications are called selective serotonin reuptake inhibitors (SSRIs). SSRIs include fluoxetine (Prozac), citalopram (Celexa), sertraline (Zoloft) and several others. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are similar to SSRIs and include venlafaxine (Effexor) and duloxetine (Cymbalta). SSRIs and SNRIs are more popular than the older classes of antidepressants, such as tricyclics–named for their chemical structure–and monoamine oxidase inhibitors (MAOIs) because they tend to have fewer side effects. However, medications affect everyone differently–no one–size–fits–all approach to medication exists. Therefore, for some people, tricyclics or MAOIs may be the best choice.

People taking MAOIs must adhere to significant food and medicinal restrictions to avoid potentially serious interactions. They must avoid certain foods that contain high levels of the chemical tyramine, which is found in many cheeses, wines and pickles, and some medications including decongestants. MAOIs interact with tyramine in such a way that may cause a sharp increase in blood pressure, which could lead to a stroke. A doctor should give a patient taking an MAOI a complete list of prohibited foods, medicines and substances.

For all classes of antidepressants, patients must take regular doses for at least three to four weeks before they are likely to experience a full therapeutic effect. They should continue taking the medication for the time specified by their doctor, even if they are feeling better, in order to prevent a relapse of the depression. Medication should be stopped only under a doctor's supervision. Some medications need to be gradually stopped to give the body time to adjust. Although antidepressants are not habit–forming or addictive, abruptly ending an antidepressant can cause withdrawal symptoms or lead to a relapse. Some individuals, such as those with chronic or recurrent depression, may need to stay on the medication indefinitely.

In addition, if one medication does not work, patients should be open to trying another. NIMH–funded research has shown that patients who did not get well after taking a first medication increased their chances of becoming symptom–free after they switched to a different medication or added another medication to their existing one. ^26,27

Sometimes stimulants, anti–anxiety medications, or other medications are used in conjunction with an antidepressant, especially if the patient has a co–existing mental or physical disorder. However, neither anti–anxiety medications nor stimulants are effective against depression when taken alone, and both should be taken only under a doctor's close supervision.

What are the side effects of antidepressants?

Antidepressants may cause mild and often temporary side effects in some people, but they are usually not long–term. However, any unusual reactions or side effects that interfere with normal functioning should be reported to a doctor immediately.

The most common side effects associated with SSRIs and SNRIs include:

• Headache–usually temporary and will subside.

• Nausea–temporary and usually short–lived.

• Insomnia and nervousness (trouble falling asleep or waking often during the night)–may occur during the first few weeks but often subside over time or if the dose is reduced.

• Agitation (feeling jittery).

• Sexual problems–both men and women can experience sexual problems including reduced sex drive, erectile dysfunction, delayed ejaculation, or inability to have an orgasm.

Tricyclic antidepressants also can cause side effects including:

• Dry mouth-it is helpful to drink plenty of water, chew gum, and clean teeth daily.

• Constipation-it is helpful to eat more bran cereals, prunes, fruits, and vegetables.

• Bladder problems–emptying the bladder may be difficult, and the urine stream may not be as strong as usual. Older men with enlarged prostate conditions may be more affected. The doctor should be notified if it is painful to urinate.

• Sexual problems–sexual functioning may change, and side effects are similar to those from SSRIs.

• Blurred vision–often passes soon and usually will not require a new corrective lenses prescription.

• Drowsiness during the day–usually passes soon, but driving or operating heavy machinery should be avoided while drowsiness occurs. The more sedating antidepressants are generally taken at bedtime to help sleep and minimize daytime drowsiness.

FDA Warning on antidepressants

Despite the relative safety and popularity of SSRIs and other antidepressants, some studies have suggested that they may have unintentional effects on some people, especially adolescents and young adults. In 2004, the Food and Drug Administration (FDA) conducted a thorough review of published and unpublished controlled clinical trials of antidepressants that involved nearly 4,400 children and adolescents. The review revealed that 4% of those taking antidepressants thought about or attempted suicide (although no suicides occurred), compared to 2% of those receiving placebos.

This information prompted the FDA, in 2005, to adopt a "black box" warning label on all antidepressant medications to alert the public about the potential 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. A "black box" warning is the most serious type of warning on prescription drug labeling.

The warning emphasizes that children, adolescents and young adults taking antidepressants should be closely monitored, especially during the initial weeks of treatment. Possible side effects to look for are worsening depression, suicidal thinking or behavior, or any unusual changes in behavior such as sleeplessness, agitation, or withdrawal from normal social situations.

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.²⁸ The study was funded in part by the National Institute of Mental Health.