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Antidepressants

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 above. The drug should not be used when there is a past history of seizures or a family history of epilepsy.

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).

KEY TERMS

Monoamine oxidase (MAO) inhibitors A type of antidepressant that works by blocking the action of a chemical substance known as monoamine oxidase in the nervous system.

Selective serotonin reuptake inhibitors (SSRIs) A class of antidepressants that work by blocking the reabsorption of serotonin in the brain, thus raising the levels of serotonin. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil).

Tricyclic antidepressant A class of antidepressants, named for their three-ring structure, that increase the levels of serotonin and other brain chemicals. They are used to treat depression and anxiety disorders, but have more side effects than the newer class of antidepressants called selective serotonin reuptake inhibitors (SSRIs).

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): 54754.

ORGANIZATIONS

National Alliance for the Mentally Ill. Colonial Place Three, 2107 Wilson Blvd., Suite 300, Arlington, VA 222013042. Web site: <www.nami.org>.

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

WEB SITES

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

National Mental Health Association. Available online at <www.mentalhealth.org> (accessed October 16, 2004).

Deanna M. Swartout-Corbeil, RN

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"Antidepressants." Gale Encyclopedia of Children's Health: Infancy through Adolescence. . Encyclopedia.com. 22 Jul. 2017 <http://www.encyclopedia.com>.

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"Antidepressants." Gale Encyclopedia of Children's Health: Infancy through Adolescence. . Retrieved July 22, 2017 from Encyclopedia.com: http://www.encyclopedia.com/medicine/encyclopedias-almanacs-transcripts-and-maps/antidepressants

Antidepressants

ANTIDEPRESSANTS

Depression in older adults is now being recognized as a severe and widespread health problem. Despite the availability of newer and safer antidepressants, depression is often unrecognized and undertreated in this population. Currently, there are several classes of antidepressants available for treatment of depression. They could be classified as monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and the miscellaneous group.

Monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) were the original antidepressants. MAOIs are very potent but more risky to use, particularly in older patients. MAOIs work by blocking the enzyme monoamine oxidase either reversibly or irreversibly. MAOIs that block the enzyme irreversibly are Iproniazid, Phenelzine, and Tranylcypromine. While taking these medications, patients have to avoid certain food products such as cheese (which contain higher levels of tyramine) as well as many over-the-counter cold medications. In combination with MAOIs these drug-food and drug-drug interactions may cause alarming increases in blood pressure and could be lethal. Since safer antidepressants are available now, these medications are seldom used.

Reversible inhibitors of monoamine oxidase, such as moclobemide and selegiline (only at lower doses) were introduced with the claim that they may not have the dangerous interactions like the irreversible MAOIs. Nonetheless, recent reports suggest that they should also be used very cautiously.

Tricyclic antidepressants (TCAs)

Tricyclic antidepressants (TCAs) work by increasing the availability of the neurotransmitters norephinephrine and serotonin in the synaptic space between nerve cells in the brain. Until recently this group of antidepressants was the "gold standard" in the treatment of late-life depression and is still used as a standard to compare newer antidepressants. This group includes medication such as amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotyline, nortriptyline, protriptyline, and trimipramine. Medications in this group have been shown to slow conduction of electrical impulses in the heart and could be lethal if a patient were to overdose with them. The TCAs also have anticholinergic side effects (dry mouth, blurred vision, constipation, urinary retention, etc.) to which older patients are very sensitive and thus are not currently used as first-line medication for late-life depression. Despite this, nortriptyline is the best studied antidepressant for acute and continuation treatment of depression in older patients. If nortriptyline is used, it is essential that plasma concentrations be monitored, since there is a proven blood level range at which it is effective and safe. It is also recommended that the electrocardiogram (ECG) be assessed prior to starting and during treatment.

Common side effects of the TCAs include dry mouth, urinary retention, confusion, constipation, blurred vision, dizziness (may lead to falls and fractures), and sedation.

Selective serotonin reuptake inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) act by increasing the concentration of serotonin available to nerve cells. Currently the most prescribed antidepressants in the world, this group includes of citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. The SSRIs are safer and better tolerated than MAOIs and TCAs. There is still some lingering controversy as to whether they are as potent as the older antidepressants for very severe depression. The SSRIs are generally not lethal in overdose, which is a significant benefit in the elderly depressed patients who are at the highest risk for suicide. The common side effects of SSRIs include nausea, vomiting, diarrhea, headaches, anxiety, sexual problems, and sleeplessness. Usually the side effects are temporary in nature. In elderly people, fluoxetine has been reported to cause some weight loss, agitation, and also stays in the body for a long time. Also, it should be noted that fluvoxamine is not approved by the FDA (Food and Drug Administration) for the treatment of depression. Medications in this group are also known to interact with other drugs often causing a reduced metabolic breakdown. Of the available SSRIs, citalopram and sertraline have relatively lesser drug interactions and are well tolerated in older people. These medications are also associated with some unusual side effects predominantly in elderly people. One such side effect is the decrease in sodium in the blood (hyponatremia). The other is the report of higher incidence of Parkinson's diseaselike movement problems in elderly people. There have been some recent reports of falls in elderly patients even with the use of SSRIs (which were previously thought not to increase the risk of falls in the elderly when compared to TCAs).

Miscellaneous

There are other antidepressants that do not belong to the previous categories mentioned and are grouped together here.

There is some data showing that the antidepressant buproprion is effective in late-life depression. It is thought to work by increasing the amount of dopamine available to the brain nerve cells and hence may be an attractive alternative medication. It has few interactions with other medications and fewer sexual side effects compared to the SSRIs but there is some concern for seizures at higher doses.

Nefazodone works somewhat like the SSRIs, but also has some other specific pathways through which it acts. Limited information is available at this time about the effectiveness of this medication in late-life depression. It can cause some very serious drug interactions.

Venlafaxine works by increasing both norepinephrine and serotonin, as do the TCAs. However, it is much more selective than the TCAs in affecting other nerve systems, which contribute to side effects. Nonetheless increases in blood pressure and nausea may be significant problems for some patients when using this medication.

Mirtazapine works at multiple sites in the brain to induce its antidepressant effect. There is information that it may help older patients, particularly those at risk of significant weight loss. Mirtazapine does increase appetite and also causes sedation, which may actually be helpful for some older people.

Methylphenidate is not considered an antidepressant but is sometimes used for older depressed people who are significantly withdrawn and lack motivation. Therefore it may be particularly useful in older depressed people undergoing rehabilitation. Limited data is available for its effect in depression.

St. John's Wort, a popular herbal remedy for mild to moderate depression, has not yet been thoroughly evaluated in older adults. However, St. John's Wort has recently been found to cause important drug interactions for many medications commonly used in the elderly, such as digoxin.

LalithKumar K. Solai Bruce G. Pollock

See also Depression; Electroconvulsive Therapy; Interpersonal Therapy; Problem Solving Therapy.

BIBLIOGRAPHY

Dunner, D. L. "Therapeutic Consideration in Treating Depression in the Elderly." Journal of Clinical Psychiatry 55 (1994): 4857.

Georgotas, A.; Mccue, R. E.; Hapworth, W.; Friedman, E.; Kim, M.; Welkowitz, J.; Chang, I.; and Cooper, T. B. "Comparative Efficacy and Safety of MAOIs Versus TCAs in Treating Depression in the Elderly." Biological Psychiatry 21 (1986): 11551166.

Glassman, A. H., and Roose, S. P. "Risks of Antidepressants in the Elderly: Tricyclic Antidepressants and Arrhythmia-Revising Risks." Gerontology 40 (1994): 1520.

Lebowitz, B. D.; Pearson, J. L.; Schneider, L. S.; Reynoldsiii, C. F.; Alexopoulos, G. S.; Bruce, M. L.; Conwell, Y.; Katz, I. R.; Meyers, B. S.; Morrison, M. F.; Mossey, J.; Niederehe, G.; and Parmelee, P. "Diagnosis and Treatment of Depression in Late Life: Consensus Statement Update." Journal of the American Medical Association 278 (1997): 11861190.

Leo, R. J. "Movement Disorders Associated with the Serotonin Selective Reuptake Inhibitors." Journal of Clinical Psychiatry 57 (1996): 449454.

Newhouse, P. A. "Use of Selective Serotonin Reuptake Inhibitors in Geriatric Depression." Journal of Clinical Psychiatry 57 (1996): 1222.

Reynoldsiii, C. F.; Frank, E.; Perel, J. M.; Mazumdar, S.; and Kupfer, D. J. "Maintenance Therapies for Late-Life Recurrent Major Depression: Research and Review Circa." International Psychogeriatrics 7 (1995): 2739.

Richelson, E. "Synaptic Effects of Antidepressants." Journal of Clinical Psychopharmacology 16 (1996): 19.

Schneider, L. S. "Pharmacological Considerations in the Treatment of Late-Life Depression." American Journal of Geriatric Psychiatry 4 (1996): 5165.

Solai, L. K.; Mulsant, B. H.; and Pollock, B. G. "Update on the Treatment of Late-Life Depression." In The Psychiatric Clinics of North AmericaAnnual of Drug Therapy. Edited by David L. Dunner and J. F. Rosenbaum. Philadelphia: W. B. Saunders Co., 1999: Pages 7392.

Thapa, P. B.; Gideon, P.; Cost, T. W.; Milam, A. B.; and Ray, W. A. "Antidepressants and the Risk of Falls among Nursing Home Residents." New England Journal of Medicine 339 (1998): 875882.

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Antidepressants

Antidepressants

Medications used to treat depression.

The two most common types of antidepressants are tricyclic antidepressants (TCAs) and selective serotonin re-uptake inhibitors (SSRIs). Examples of TCAs include nortriptyline (also known by the brand name Pamelor), imipramine (Tofranil), and desipramine (Norpramin). Examples of SSRIs include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). Clinical studies have shown that some people benefit from these medications.

Tricyclic antidepressants (TCAs)

Before using TCAs, it is necessary to have a medical history and examination of the patient, including an electrocardiogram (EKG). Not everyone develops side effects when taking TCAs, but the most common side effects include: dry mouth, impaired ability to focus vision at close range, constipation, urinary hesitation, dizziness, weight gain, and sedation. TCAs may produce minor cardiovascular changes such as orthostatic hypotension (low blood pressure when the person stands up, often causing light-headedness), hypertension, rapid heart beat, and minor changes in the electrical activity of the heart, which may show in the electrocardiogram (EKG). Most of these side effects can be minimized by slowly adjusting the dose of the drug.

During treatment with TCAs, patients should be monitored by a physician trained in the management of these medications. It is recommended that he or she perform regular blood pressure, heart rate, and EKG monitoring. TCAs may interact with other medications the patient is taking, so it is important to consult a doctor before doing so. Finally, the TCAs should not be stopped abruptly, as this may induce mild withdrawal side effects (malaise, chills, stomachache, flu-like symptoms). Though they are safe if carefully monitored and taken as prescribed, TCAs can be lethal if taken in overdose.

Selective serotonin re-uptake inhibitors (SSRIs)

The reports that SSRIs are effective in treating adults with major depressive disorder (MDD), together with the findings that SSRIs have a relatively benign side effect profile, low lethality after an overdose, and once-a-day administration, have encouraged the use of SSRIs.

Several studies have reported 70-90% response rate to fluoxetine or sertraline for the treatment of adolescents with major depressive disorder, but the results of these studies are not conclusive because they have methodological limitations. A recent, large, well-performed investigation showed that fluoxetine was more effective for the treatment of depressed children and adolescents than a placebo. Despite the significant response to fluoxetine, many patients had only partial improvement.

Overall, the SSRIs have similar effectiveness and side effects as TCAs. The most common side effects include nausea, stomachache, diarrhea, headaches, mild tremors, sweating, sleep disturbance, sedation, restlessness, lack of appetite, decreased weight, vivid dreams , and sexual dysfunction (inability to have an orgasm or delayed ejaculation). Most of these side effects are temporary and may be diminished by reducing the dose or discontinuing the medication. There are no specific laboratory tests required before administering SSRIs. These drugs do have potentially harmful interactions with several commonly prescribed drugs; therefore, all physicians should be informed if someone is taking an SSRI.

Patients who do not respond to treatment

The most common reasons for failure of treatment are inadequate medication dosage or length of medication trial, lack of compliance with treatment, exposure to chronic or severe life events that require different modalities of therapy, existence of other psychiatric disorders (e.g., substance abuse, anxiety disorder), and misdiagnosis. In adults with resistant depression , several types of combinations of medications and ECT (electroconvulsive therapy ) have been found to be useful.

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antidepressant

antidepressant, any of a wide range of drugs used to treat psychic depression. They are given to elevate mood, counter suicidal thoughts, and increase the effectiveness of psychotherapy. Before the introduction of such drugs in the late 1950s, most patients with major depression had no recourse but hospitalization; only 45% improved after one year. In contrast, 80%–90% of such patients can expect significant relief from depression with one of the medications now prescribed.

Antidepressants act on the flow of the neurotransmitters epinephrine, serotonin, and norepinephrine across neural synapses. Common antidepressants include monamine oxidase inhibitors (MAOIs) such as isocarboxazid (Marplan), tricyclics such as imipramine (Tofranil) and amitriptyline (Elavil), and the newer selective serotonin reuptake inhibitors (SSRIs) as fluoxetine (Prozac) and sertraline HCL (Zoloft). Venlafaxine (Effexor) inhibits both serotonin and norepinephrine reuptake.

The choice of antidepressant often has more to do with its side effects (variously sedation, constipation, hypotension, tachycardia, weight gain, sexual dysfunction) than efficacy, as they are generally regarded to be equally effective. The newer drugs, especially SSRIs, are tolerated better and are currently by far the most widely prescribed, but SSRIs also appear to be less effective in children and teenagers and may cause some of them to become suicidal.

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Antidepressant

ANTIDEPRESSANT

Antidepressants are a diverse group of drugs that demonstrate a capacity to produce improvement in the symptoms of clinical depression, and they are used to treat the abnormal mood states that characterize depressive illnesses. The word depression is used commonly to describe a state of sadness; but health professionals use the term in a more restricted or defined manner to describe several psychiatric disorders characterized by abnormal moods. One of these is bipolar disorder, in which periods of depression (marked by dejection, lack of energy, inactivity, and sadness) alternate with periods of manic behavior (marked by abnormally high energy levels and increased activity). Another is major depression, which is often a recurring problem characterized by severe and prolonged periods of depression without the manic swing. A third is dysthymia, a chronic mood state characterized by depression and irritability, which was once referred to as depressive neurosis. The signs and symptoms of depressive mood disorders may occur as part of other medical and psychiatric disorders (i.e., following stroke); as a result of endocrine disorders; or as a consequence of excessive drug use. Often these abnormal mood states may not meet established criteria for one of the major psychiatric mood disorders, but they may nevertheless respond to one of the antidepressant drugs.

Antidepressants can also be useful in a number of medical and psychiatric disorders where depression is not the major feature. For example, some categories of antidepressants can be used to treat anxiety and panic disorders, and they are often useful as adjunctive medications for chronic pain. Antidepressant drugs are not generally helpful for short-term depressed moods that are part of everyday life or for the normal period of grief that follows the loss of a loved one.

New categories of antidepressants are being continuously developed and tested. There are now at least five categories in use. These include tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, lithium, nontricyclic antidepressants, and serotonin-reuptake inhibitors (SSRIs). The chemical structures of some of these are shown below.

The tricyclic antidepressants, which have been used for many years in the treatment of depression, include such compounds as imipramine (Tofranil), nortriptyline (Aventyl), and desipramine (Norpramin). In addition to being used to treat depression, imipramine is sometimes used to treat alcoholism and cocaine withdrawal. Desipramine is also sometimes used to treat depression associated with cocaine withdrawal. In terms of dosage, most of the tricyclics can be given in a single dose at bedtime. The tricyclics as a group, however, have two major drawbacks. First, the patient must take a specific tricyclic for a period of 2 to 4 weeks before signs of clinical effectiveness occur. Second, the tricyclics have a relatively narrow margin of safety, which means that it is easier for a depressed patient to take an overdose. As a rule, physicians are cautious about prescribing tricyclic antidepressants if the patient appears to be at risk for suicide.

The monoamine oxidase (MAO) inhibitors are generally used as second-line drugs for depressed patients who do not respond to tricyclics, because they require certain dietary restrictions (patients are not allowed liver, aged meats, most cheeses, red wine, soy sauce, etc.) The MAO inhibitors are, however, first-choice drugs for treatment of panic disorder and of depression in the elderly. They include phenelzine sulfate (Nardil), isocarboxazid (Marplan), and tranylcypromine sulfate (Parnate). These antidepressants may be given in either the morning or the evening, depending on their effect on the patient's sleep.

Although lithium (Eskalith, Lithonate) is useful in treating manic states and in preventing depression in bipolar disorders, it is not generally used for other types of depression. Lithium may have serious side effects and may be toxic at high dosages. Exposure to lithium in early pregnancy is associated with an increased frequency of birth defects, and the long-term use of lithium damages kidney function. It also seems to have no significant value in treating cocaine dependence or alcoholism.

The serotonin reuptake inhibitors (SSRIs) are the newest category of antidepressant medications. They have become the most widely used drugs for depression; fluoxetine (Prozac) has been the best-selling antidepressant since the mid-1990s. Other SSRIs include paroxetine (Paxil) and sertraline (Zoloft). A fourth drug, bupropion (Wellbutrin), is not an SSRI but is often grouped with them because it is a newer antidepressant. The SSRIs have several advantages: They can often nip mild depression "in the bud" before it develops into a major depressive episode. They can also be used to treat bulimia, obesity, and obsessive-compulsive disorder as well as depression. Since insomnia is a common side effect of SSRIs, they are usually given as a single dose in the morning. The SSRIs also have several disadvantages, including a long response time (patients may need to wait 4 weeks to see any improvement); the same failure rate as the older tricyclics (20-40percent of patients); side effects that include sexual dysfunction; and high cost ($2-3 per tablet).

When a patient does not respond to a specific antidepressant after a trial of 2 to 4 weeks, the physician may prescribe another medication. If the new drug is from the same group as the first antidepressant, the physician can rapidly decrease the dosage of the first drug while increasing the dosage of the second. If, however, the new antidepressant is from a different category, a "washout time" must be allowed in order to prevent drug interactions. A washout period of 2 to 3 weeks is necessary when the patient is switched from an MAO inhibitor to a tricyclic; a period of 4 to 5 weeks is necessary when switching from an SSRI to an MAO inhibitor.

BIBLIOGRAPHY

American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders, 4th ed. (DSM-IV). Washington, DC.

Baldessarini, R. J. (1991). Drugs and the treatment of psychiatric disorders. In: A. G. Gilman et al. (Eds.), Goodman and Gilman's the pharmacological basis of therapeutics, 8th ed. New York: Pergamon.

Eisendrath, S. J. (1998). Psychiatric Disorders. In L. M. Tierney et al. (Eds.), Current Medical Diagnosis & Treatment, 37th ed. Stamford, CT: Appleton & Lange.

George R. Uhl

Valina Dawson

Revised by Rebecca J. Frey

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antidepressant

antidepressant (anti-di-press-ănt) n. a drug that alleviates the symptoms of depression. A widely prescribed group are the tricyclic antidepressants (TCAs), such as doxepin and imipramine. Side-effects include dry mouth, blurred vision, and difficulty in urination. See also MAO inhibitor, SNRI, SSRI.

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antidepressant

an·ti·de·pres·sant / ˌantēdəˈpresnt; ˌantī-/ • adj. (chiefly of a drug) used to alleviate depression. • n. an antidepressant drug.

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