Selective Serotonin Reuptake Inhibitors

Definition

Selective serotonin reuptake inhibitors are medicines that relieve symptoms of depression.

Purpose

Selective serotonin reuptake inhibitors are used to treat serious, continuing depression that interferes with a person's ability to function. Like other antidepressant drugs, they help reduce the extreme sadness, hopelessness, and lack of interest in life that are typical in people with depression. Selective serotonin reuptake inhibitors also are used to treat panic disorder, obsessive compulsive disorder (OCD), and have shown promise for treating a variety of other conditions, such as premenstrual syndrome, eating disorders, obesity, self-mutilation, and migraine headache.

As of late 2003, SSRIs have been found to have other off-label applications, including treatment of premature ejaculation and diabetic neuropathy.

Description

Selective serotonin reuptake inhibitors, also known as SSRIs or serotonin boosters, are thought to work by correcting chemical imbalances in the brain. Normally, chemicals called neurotransmitters carry signals from one nerve cell to another. These chemicals are constantly being released and taken back up at the ends of nerve cells. Selective serotonin reuptake inhibitors act on one particular neurotransmitter, serotonin, reducing its re-entry into nerve cells and thus allowing serotonin to build up. Although scientists are not exactly sure how it works, serotonin is involved in the control of moods, as well as other functions such as sleep, body temperature, and appetite for sweets and other carbohydrates. Somehow, drugs that prevent the uptake of serotonin improve the moods of people with serious depression, OCD, and some types of anxiety disorders.

Selective serotonin reuptake inhibitors are available only with a doctor's prescription and are sold in tablet, capsule, and liquid forms. Commonly used selective serotonin reuptake inhibitors are fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox).

Recommended dosage

The recommended dosage depends on the type of SSRI and the type and severity of depression for which it is being taken. Dosages may be different for different people. It is important for people taking SSRIs to take the drug exactly as prescribed. Taking larger or more frequent doses or taking the drug for longer than directed, for example, can cause unwanted effects.

SSRIs are about as effective as other antidepressants. About 60-80% of people taking the drugs as directed will find that their conditions improve. However, it may take four weeks or more for the effects of this medicine to be felt. Therefore, when people begin SSRI therapy, it is important to continue taking the medication, even if an improvement in mood doesn't begin immediately.

People who take SSRIs should ask their doctors about how to stop taking the medication. Usually, doctors advise patients to taper down gradually to reduce the chance of withdrawal symptoms or SSRI discontinuation syndrome.

SSRIs may be taken with food to prevent stomach upset.

Precautions

There have been reports that some patients taking SSRIs have an increase in thoughts about suicide. It is not clear whether the medicine causes this effect because suicidal thoughts are very often a part of depression itself. While some patients may experience worsening of such thoughts early in the treatment of their depression, there is no credible evidence that SSRIs alone cause people to become suicidal or violent.

Serious and possibly life-threatening reactions may occur when SSRIs are used in combination with monoamine oxidase inhibitors (MAO inhibitors), such as Nardil and Parnate, which also are used to treat depression. These reactions also are possible when a person stops taking an SSRI and immediately begins taking an MAOI. SSRIs and MAO inhibitors should never be taken at the same time. When switching from an SSRI to an MAOI or vice versa, it may be necessary to allow two to five weeks or more between stopping one and starting the other. The physician prescribing the medications should tell the patient exactly how much time to allow before beginning the other medication.

People with a history of manic disorders should use any antidepressant, including an SSRI, with caution.

It is important to see a doctor regularly while taking SSRIs. The doctor will check to make sure the medicine is working as it should and will watch for unwanted side effects. The doctor may also need to adjust the dosage during this period.

Some people feel drowsy, dizzy, or lightheaded when using SSRIs. The drugs may also cause blurred vision in some people. Since SSRIs can sometimes cause drowsiness, driving or operating heavy machinery should be undertaken cautiously, particularly when the person first begins taking the medication.

These medicines make some people feel lightheaded, dizzy, or faint when they get up after sitting or lying down, a condition known as orthostatic hypotension. People may try to lessen the problemby getting up gradually and holding onto something for support if possible. If the problem is severe or doesn't improve, the patient should discuss it with his or her doctor.

Because SSRIs work on the central nervous system, they may add to the effects of alcohol and other drugs that slow down the central nervous system, such as antihistamines, cold medicine, allergy medicine, sleep aids, medicine for seizures, tranquilizers, some pain relievers, and muscle relaxants. They may also add to the effects of anesthetics, including those used for dental procedures. Anyone taking SSRIs should check with his or her doctor before taking any of the drugs mentioned above.

SSRIs may occasionally cause dry mouth, although this side effect is much more common with an older class of antidepressants known as tricyclics. To temporarily relieve the discomfort, doctors sometimes suggest chewing sugarless gum, sucking on sugarless candy or ice chips, or using saliva substitutes, which come in liquid and tablet forms and are available without a prescription. If the problem continues for more than two weeks, check with a doctor or dentist. Mouth dryness that continues over a long time may contribute to tooth decay and other dental problems.

Changes in sexual functioning are among the more common side effects with SSRIs. Depending on the particular SSRI prescribed, 8-15% of patients may report these side effects. The most common problem for men is delayed ejaculation. Women may be unable to have orgasms. A doctor should be contacted if any changes in sexual functioning occur.

Special conditions

People with certain medical conditions or who are taking certain other medicines can have problems if they take SSRIs. Before taking these drugs, a patient should let the doctor know about any of these conditions:

ALLERGIES. Anyone who has had unusual reactions to SSRIs in the past should let his or her doctor know before taking the drugs again. The doctor should also be told about any allergies to foods, dyes, preservatives, or other substances.

PREGNANCY. In studies of laboratory animals, some SSRIs have caused miscarriage and other problems in pregnant females and their offspring. However, at least two studies in humans (by Pastuszak in 1993 and Kuhlin in 1998) have shown SSRIs to be safe during pregnancy, and newer studies done in 2003 have reported that SSRIs do not appear to increase the risks of birth defects in the offspring. Still, women who are pregnant or who may become pregnant should check with their doctors before using SSRIs.

BREASTFEEDING. SSRIs pass into breast milk and some may occasionally cause unwanted side effects in nursing babies whose mothers take the drugs. These effects include vomiting, watery stools, crying, and sleep problems. Women who are breastfeeding should talk to their doctors about the use of SSRIs. They may need to switch to a different medicine while breastfeeding. If SSRIs must be taken, it may be necessary to stop breastfeeding while being treated with these drugs. However, several studies in people (for example, Yoshida in 1998) have indicated that SSRIs in breast milk have no effect on infant development.

DIABETES. SSRIs may affect blood sugar levels. People with diabetes who notice changes in their blood or urine tests while taking this medicine should check with their doctors.

OTHER MEDICAL CONDITIONS. Before using SSRIs, people with any of these medical problems should make sure their doctors are aware of their conditions: diabetes, kidney disease, liver disease, seizure disorders, current or past drug abuse or dependence, or diseases or conditions that affect the metabolism or blood circulation.

Side effects

The most common side effects are anxiety and nervousness (reported by 5-13% of people taking various SSRIs), tremor (5-14%), trouble sleeping (2-8%), tiredness or weakness (4-15%), nausea (11-26%), diarrhea (11-26%), constipation (1-8%), loss of appetite (3-18%), weight loss (1-13%), dry mouth (10-22%), headache (1-5%), sweating (5-9%), trouble urinating (1-2%), and decreased sexual ability (8-15%). Many of these problems diminish or disappear as the body adjusts to the drug and do not require medical treatment unless they interfere with normal activities. Persistent problems, such as sexual dysfunction, should be discussed with the doctor.

More serious side effects are possible, but extremely rare. People taking SSRIs who notice unusual joint or muscle pain; breathing problems; chills or fever ; excessive excitement, fast talking, or actions that are out of control; or mood swings should contact their doctors. People who develop skin rashes or hives after taking an SSRI should stop taking the medication and contact their doctors as soon as possible. Other rare side effects may occur. Anyone who has unusual symptoms after taking an SSRI should get in touch with his or her doctor.

Side effects may continue for some time after treatment with this medicine ends. How long the effects continue depends on how long the drug was taken and how much of it was used. In most cases, doctors recommend that patients taper off SSRIs rather than abruptly stopping them, because of the risk of developing a condition known as SSRI discontinuation syndrome. This syndrome can mimic serious illness. People who experience agitation, confusion, or restlessness; dizziness or lightheadedness; vision problems; tremor; sleep problems; unusual tiredness or weakness; nausea and vomiting or diarrhea; headache; excessive sweating; runny nose; or muscle pain for more than a few days after stopping or tapering an SSRI should consult their doctors.

Interactions

SSRIs may interact with other medicines. When this happens, the effects of one or both of the drugs may change or the risk of side effects may be greater. Anyone who takes SSRIs should let the doctor know about all other medicines he or she is taking. Among the drugs that may interact with SSRIs are:

• such central nervous system (CNS) depressants as medicine for allergies, colds, hay fever, and asthma ; sedatives; tranquilizers; prescription pain medicine; muscle relaxants; medicine for seizures; sleep aids; barbiturates ; and anesthetics.
• blood thinners (anticoagullants)
• such monoamine oxidase inhibitors (MAOIs) as Nardil or Parnate, used to treat conditions including depression and Parkinson's disease
• the antiseizure drug phenytoin (Dilantin)
• the food supplement (and sleep aid) tryptophan, which has been withdrawn from the United States market, but may be found in some herbal preparations
• digitalis and other heart medicines
• St. John's wort (Hypericum perforatum ). St. John's wort is a herb used in Europe and the United States to relieve mild-to-moderate symptoms of depression. Research indicates that it acts as an SSRI and not as an MAO inhibitor, as previously believed. People who are using St. John's wort to relieve depression should not take a prescription SSRI at the same time.

The list above does not include every drug that may interact with SSRIs. Patients should be sure to check with a doctor or pharmacist before combining SSRIs with any other prescription or nonprescription (over-the-counter) medicine, including herbal preparations.

KEY TERMS

Anesthetic— Medicine that causes a loss of feeling, especially of pain. Some anesthetics also cause a loss of consciousness.

Anxiety— Worry or tension in response to real or imagined stress, danger, or dreaded situations. Physical reactions, such as fast pulse, sweating, trembling, fatigue, and weakness may accompany anxiety.

Central nervous system— The brain and spinal cord.

Depression— A mental condition in which people feel extremely sad and lose interest in life. People with depression may also have sleep problems and loss of appetite and may have trouble concentrating and carrying out everyday activities.

Metabolism— All the physical and chemical changes that occur in cells to allow growth and maintain body functions. These include processes that break down substances to yield energy and processes that build up other substances necessary for life.

Obsessive-compulsive disorder— An anxiety disorder in which people cannot prevent themselves from dwelling on unwanted thoughts, acting on urges, or performing repetitious rituals, such as washing their hands or checking to make sure they turned off the lights.

Off-label application— The use of a prescription medication to treat conditions outside the indications approved by the Food and Drug Administration (FDA).

Premenstrual syndrome— (PMS) A set of symptoms that occur in some women 2-14 days before they begin menstruating each month. Symptoms include headache, fatigue, irritability, depression, abdominal bloating, and breast tenderness.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Depression (Unipolar Disorder)." Section 15, Chapter 189 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Pelletier, Dr. Kenneth R. The Best Alternative Medicine, Part I: Western Herbal Medicine. New York: Simon and Schuster, 2002.

Pies, Ronald W. Handbook of Essential Psychopharmacology. Washington, DC: American Psychiatric Press, Inc.

PERIODICALS

Aronson, Sarah A., MD. "Depression." eMedicine December 31, 2003. 〈http://www.emedicine.com/med/topic532.htm〉.

Ditto, K. E. "SSRI Discontinuation Syndrome. Awareness as an Approach to Prevention." Postgraduate Medicine 114 (August 2003): 79-84.

Nonacs, R., and L. S. Cohen. "Assessment and Treatment of Depression During Pregnancy: An Update." Psychiatric Clinics of North America 26 (September 2003): 547-562.

Roose, S. P. "Treatment of Depression in Patients with Heart Disease." Biological Psychiatry 54 (August 1, 2003): 262-268.

Stone, K. J., A. J. Viera, and C. L. Parman. "Off-Label Applications for SSRIs." American Family Physician 68 (August 1, 2003): 425-427.

ORGANIZATIONS

American Psychiatric Association (APA). 1400 K Street, NW, Washington, DC 20005. (888) 357-7924. 〈http://www.psych.org〉.

National Center for Complementary and Alternative Medicine (NCCAM) Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898-7923. (888) 644-6226. 〈http://nccam.nih.gov〉.

National Institute of Mental Health (NIMH). 6001 Executive Boulevard, Room 8184, MSC 9663, Bethesda, MD 20892-9663. (301) 443-4513. 〈www.nimh.nih.gov.〉.

U. S. Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857. (888) 463-6332. 〈http://www.fda.gov〉.