Antidepressants

Definition

An antidepressant is a medication used primarily in the treatment of depression. Depression can occur if some of the chemicals called neurotransmitters in the brain are not functioning effectively. There are three specific chemicals that can affect a person's mood: serotonin, norepinephrine, or dopamine. Antidepressants affect one or more of these chemicals in different ways to help stabilize the chemical imbalance often seen in depression. Antidepressant drugs are not happy pills, and they are not a panacea. They are prescription-only drugs that come with risks as well as benefits and should only be taken under a doctor's supervision. Because children and adolescents experience depression just as adults do, they are sometimes prescribed antidepressants by their physician.

Description

Antidepressants are medicines used to help people who have depression. Antidepressant medications may be indicated for those children and adolescents with bipolar depression, psychotic depression, depression with severe symptoms that prevent effective psychotherapy or counseling, and depression that does not respond to psychotherapy. However, given the psychosocial dynamics that often coexist with depression, antidepressants are usually insufficient as the only treatment for children who have the disorder. Psychotherapy is often recommended as an adjunct treatment along with the prescribed antidepressant. The use of antidepressants among children has been growing steadily since the late 1980s.

All antidepressant medications have a slow onset of action, typically three to five weeks. Although side effects may be observed as early as the first dose, significant therapeutic improvement is always delayed. Most antidepressants are believed to work by slowing the removal of certain chemicals from the brain. These chemicals are called neurotransmitters, which are needed for normal brain function. Antidepressants help people with depression by making these natural chemicals more available to the brain. There are many different kinds of antidepressants, including the ones listed below.

Monoamine oxidase (MAO) inhibitors

MAO inhibitors work by blocking the action of a chemical substance known as monoamine oxidase in the nervous system. Studies done in animals suggest that MAO inhibitors may slow growth in children. Little information on the use of MAO inhibitors in children under 16 years old was available as of 2004.

Tricyclics

Tricyclics have been used to treat depression for a long time. They include amitriptyline, desipramine, imipramine, nortriptyline, and trimipramine. Tricyclic anti-depressants work by shoring up the brain's supply of norepinephrine and serotonin, chemicals that are abnormally low in depressed patients. This effect allows the flow of nerve impulses to return to normal. The tricyclics do not act by stimulating the central nervous system or by blocking monoamine oxidase.

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs are a group of antidepressants that includes drugs such as citalopram (Celexa), fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and escitalopram (Lexapro). In the early 2000s SSRIs have replaced tricyclic antidepressants as the drugs of choice in the treatment of depressive disorders, primarily because of their improved tolerability and safety if taken in overdose. These medicines tend to have fewer side effects than the tricyclics.

Others

There are several antidepressants available as of 2004 that, because they are not chemically structured like the other types of antidepressants, are grouped into the category "other" or miscellaneous. Bupropion (Wellbutrin), mirtazapine (Remeron), and venlafaxine (Effexor) are among those in this category.

General use

SSRIs

Selective serotonin reuptake inhibitors (SSRIs) are considered an improvement over older antidepressants because they are better tolerated and are safer if taken in an overdose. The prescription of SSRIs has risen dramatically in the past several years in children and adolescents age 10 to 19. Some research points out that this increase has coincided with a significant decrease in suicide rates in this age group, but it is unknown if SSRIs are directly responsible for this improvement. As of 2004, fluoxetine (Prozac) was the only SSRI that the Food and Drug Administration (FDA) has approved for the treatment of children's depression. Fluoxetine (Prozac), sertraline (Zoloft), and fluvoxamine (Luvox) are approved by the FDA for the treatment of obsessive-compulsive disorder because studies have shown they are safe and effective medicines for adolescents with this disorder. An early 2000s study showed that citalopram (Celexa) significantly reduced symptoms of major depression in children and adolescents. Sertraline (Zoloft) was also found in studies to be effective with youths, slightly more so for adolescents than younger children. Physicians may frequently prescribe many of the SSRI antidepressants besides fluoxetine (Prozac) for children to treat depression, even though they have not been approved for this use by the FDA. This is called "off-label" use. Off-label refers to the use by doctors of FDA-approved drugs for purposes other than those approved by the agency.

Tricyclics

Tricyclic antidepressants (TCAs) are primarily used to treat depression in adults. The most commonly used ones are nortriptyline (Pamelor), desipramine (Elavil), and imipramine (Tofranil). They function similarly and have similar risks and side effects. They are not as effective in treating depression in children who have not reached puberty, and for these children should only be used as a second line agent. There is marginal evidence to support the use of tricyclics in the treatment of depression in adolescents, but the effect is likely to be moderate. Although they are actually not very effective as antidepressants with children, they can be quite helpful for a variety of other problems, including attention deficit disorder, enuresis ( bed-wetting ), and obsessive-compulsive disorder. The American Academy of Child and Adolescent Psychiatry (AACAP) does not recommend TCAs as a first-line treatment for youths requiring medicine for depressive disorders. However, the AACAP acknowledges that some young people with depression may respond better to TCAs than to other antidepressants.

MAO inhibitors

Studies on MAO inhibitors have only been performed on adult patients, and there is as of 2004 no specific information comparing the use of MAO inhibitors in children with use in other age groups. However, animal studies have shown that these medicines may slow growth in young children and are therefore not generally recommended for use in children. Parents should be sure to speak with the doctor regarding whether the use of these medicines is appropriate before giving a monoamine oxidase inhibitor to their child.

Others

Bupropion (Wellbutrin) seems to be a better antidepressant for children than the tricyclic antidepressants. Again, as of 2004 bupropion has not been approved for this use by the FDA. It has also proven to be an effective treatment for children diagnosed with attention deficit disorder. The manufacturer of venlafaxine (Effexor) has issued a statement that the drug is not effective in treating depression in children and teenagers and is recommending that venlafaxine (Effexor) not be used in pediatric patients. Early 2000s studies have found increased reports of thinking about suicide and self-harm, among children and teens taking venlafaxine (Effexor). Mirtazapine (Remeron) must be used with caution in children with depression. Studies have shown occurrences of children thinking about suicide or attempting suicide in clinical trials for this medicine.

Precautions

In 2004, the FDA issued a health advisory recommending close observation for worsening depression in both adults and children treated with certain antidepressants. The FDA requested that a warning of a possible association between the use of SSRIs and suicidal behavior be inserted in the labeling of these medications. Studies have found no direct link between these antidepressants and worsening depression or increased suicide in children. In fact, no suicide has been reported among the more than 4,100 people studied who take SSRIs. However, the FDA continues to study this issue. Some believe the increased risk of suicide is not related to the SSRIs themselves, but a phenomenon seen when the symptoms of depression first begin to improve. This phenomenon occurs when the depressed person starts to gain more energy but is not yet fully relieved of the depressive symptoms. The drugs under review include bupropion (Wellbutrin), citalopram (Celexa), fluoxetine (Prozac), mirtazapine (Remeron), nefazodone (Serzone), paroxetine (Paxil), sertraline (Zoloft), escitalopram (Lexapro) and venlafaxine (Effexor). It should be again noted that the only drug that has received approval for use in children with major depressive disorder is fluoxetine (Prozac). Several of these drugs, including sertraline (Zoloft) and fluoxetine (Prozac) are approved for the treatment of obsessive-compulsive disorder in pediatric patients. The drug escitalopram (Lexapro) does not appear to help depressed children and adolescents, according to one clinical study.

Side effects

MAO inhibitors

MAO inhibitors have largely been supplanted in therapy because of their high risk of significant side effects, most notably severe, possibly fatal high blood pressure, if foods or alcoholic beverages containing tyramine are consumed. Other side effects include dizziness, fainting, headache, tremors, muscle twitching, confusion, memory impairment, anxiety, agitation, insomnia, weakness, drowsiness, chills, blurred vision, and heart palpitations. Treatment with MAO inhibitors should never be halted abruptly, and should not be stopped without first consulting a physician.

Tricyclics

Although TCAs have been shown to be effective in many clinical situations, their use is associated with potentially serious side effects. The most important of these is the potential for an irregular heartbeat, which can at times (though rarely) be fatal. The vast majority of TCA-related deaths happen when an overdose is taken. Physician will likely monitor blood levels, as well as perform echocardiograms to monitor heart functioning. Other side effects include dry mouth, constipation, difficulty urinating, blurred vision, sedation, weight gain, central nervous system and cardiovascular toxicity, delirium, and risk of suicide by overdose. The risk of side effects can be reduced with careful prescribing practices.

SSRIs

Several side effects are possible with SSRIs. Special care should be paid in the first few weeks of taking the prescribed drug. Should nervousness, agitation, irritability, mood instability, or sleeplessness emerge or worsen during treatment with SSRIs, parents should obtain a prompt evaluation by their doctor. Some of the side effects that can be caused by SSRIs include dry mouth, nausea, nervousness, insomnia, and headache. Those taking fluoxetine (Prozac) might also have a feeling of being unable to sit still. Children already on any of the SSRIs should remain on the drug if it has been helpful, but they should also be carefully monitored by a physician for evidence of side effects. Once begun, treatment with these medications should not be abruptly stopped, because the child may experience further agitation and restlessness. Families should not discontinue treatment without consulting their physician.

Others

Bupropion (Wellbutrin) has several side effects, including drowsiness, lightheadedness, headache, constipation, dry mouth, nausea, and vomiting. Occasionally patients may experience tiredness, muscle twitching, weight loss, blurred vision, and trouble sleeping. The main side effect is appetite suppression. In some children this may also lead to hypoglycemia (low blood sugar). It is recommended that children on Wellbutrin should eat mid-morning, mid-afternoon, and bedtime snacks in addition to the usual three meals in a manner similar to that of diabetics. The main risk of Wellbutrin is that it increases the likelihood of seizures, though the incidence is rare. Some of these seizures may be related to hypoglycemia and so may be prevented by sticking to the diet as described

The antidepressant Prozac is used to treat depressive disorders.

(© David Butow/Corbis Saba.)

Interactions

MAO inhibitors

MAO inhibitors have many dietary restrictions, and people taking them need to follow the dietary guidelines and physician's instructions very carefully. A rapid, potentially fatal increase in blood pressure can occur if foods or alcoholic beverages containing tyramine are ingested by a person already taking MAO inhibitors. Foods containing tyramine include sour cream; parmesan, mozzarella, cheddar and other cheeses; beef or chicken liver; cured meats; game meat; caviar; dried fish; bananas; avocados; raisins; soy sauce; fava beans; and caffeine-containing products like colas, coffee and tea, and chocolate. Beverages to be avoided include beer, red wine, other alcoholic beverages, non-alcoholic and reduced alcohol beer, and red wine products.

SSRIs

SSRIs should not be used with any drug that increases serotonin concentrations, including MAO inhibitors, tramadol, sibutramine, meperidine, sumatriptan, lithium, St. John's wort, ginkgo biloba, and some anti-psychotic agents. A "serotonin syndrome" may occur, where mental status changes and where agitation, sweating, shivering, tremors, diarrhea, and uncoordination, and fever may develop. This syndrome may be life-threatening. SSRIs interact with a number of other drugs that act on the central nervous system. Care should be used in combining SSRIs with major or minor tranquilizers or with anti-epileptic agents such as phenytoin (Dilantin) or carbamazepine (Tegretol).

Tricyclics

Tricylic antidepressants should not be taken with the gastric acid inhibitor cimetidine (Tagamet), since this increases the blood levels of the tricyclic compound. TCAs have many interactions, and specialized references should be consulted. Specifically, it is best to avoid other drugs with anticholinergic effects. Tricyclics should not be taken with the antibiotics grepafloxacin and sprafloxacin, since the combination may cause serious heart arrythmias.

Others

Alcohol, phenothiazines, and benzodiazepines may all increase the likelihood of seizures if consumed with bupropion (Wellbutrin).

Parental concerns

Major depression in children and adolescents is a serious condition that should be treated in a way that includes careful follow-up and monitoring. If the physician determines that medication is indicated, parents should ensure their child continues to receive ongoing assessment. Selection of an antidepressant for their child is done on an individual basis, as drugs may work differently for different people. What is effective for some may not be effective for others. If one antidepressant is ineffective, then there is probably another one that can be tried. All potentially effective treatments can be associated with side effects. A careful weighing of risks and benefits, with appropriate follow-up to help reduce risks, is the best that can be recommended.

See also Depression.

Resources

BOOKS

Mondimore, Francis Mark. Adolescent Depression. Baltimore, MD: Johns Hopkins University Press, 2002.

PERIODICALS

Ables, Adrienne Z., and Otis L. Baughman III. "Antidepressants: Update on New Agents and Indications." American Family Physician 67, no. 3 (February 1, 2003): 547–54.

ORGANIZATIONS

National Alliance for the Mentally Ill. Colonial Place Three, 2107 Wilson Blvd., Suite 300, Arlington, VA 22201–3042. Web site: http://www.nami.org.

National Mental Health Association. 2001 N. Beauregard Street, 12th Floor, Alexandria, Virginia 22311. Web site: http://www.nmha.org.

WEB SITES

National Institute of Mental Health. Available online at http://www.nimh.nih.gov/ (accessed October 16, 2004).

National Mental Health Association. Available online at http://www.mentalhealth.org (accessed October 16, 2004).

Deanna M. Swartout-Corbeil, RN