Trazodone

Definition

Trazodone is an oral antidepressant. It is sold in the United States under the brand name Desyrel and is also available under its generic name.

Purpose

Trazodone is used to treat depression and to treat the combination of symptoms of anxiety and depression. Like most antidepressants, trazodone has also been used in limited numbers of patients to treat panic disorder , obsessive-compulsive disorder , attention-deficit/hyperactivity disorder , enuresis (bed-wetting), eating disorders such as bulimia nervosa , cocaine dependency, and the depressive phase of bipolar (manic-depressive) disorder. It should be noted, however, that trazodone has not received official approval from the United States Food and Drug Administration (FDA) for these secondary uses.

Description

Trazodone acts to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. Its action primarily increases the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, blocks the action of another brain chemical, acetylcholine. Trazodone is classified as an atypical antidepressant, but it shares many of the properties of tricyclic antidepressants ( amitriptyline , clomipramine , desipramine , doxepin , imipramine , nortriptyline , protriptyline , and trimipramine ). It also shares some of the properties of selective serotonin reuptake inhibitor antidepressants ( fluoxetine , paroxetine , and sertraline ). Trazodone is the most sedating, and least anticholinergic, of all the currently marketed antidepressants.

The therapeutic effects of trazodone, like other antidepressants, appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug. People taking trazodone should be aware of this and continue taking the drug as directed even if they do not see immediate improvement.

Recommended dosage

As with any antidepressant, trazodone must be carefully adjusted by the physician to produce the desired therapeutic effect. Trazodone is available as 50-mg, 100-mg, and 150-mg film-coated tablets that cannot be divided, and 150-mg and 300-mg oral tablets that can be split. Therapy is usually started at a total of 150 mg per day divided into two or three doses. This dose is increased by 50 mg every three or four days until the desired effects are seen. Daily doses may be increased to a maximum of 400 mg per day in outpatients and up to 600 mg per day in hospitalized patients. In cases of extreme depression, daily doses of up to 800 mg have been used in hospitalized patients. To minimize daytime drowsiness, a major portion of the daily dose can be given at bedtime.

Precautions

The most common problem with trazodone is sedation (drowsiness, lack of mental and physical alertness). This side effect is especially noticeable early in therapy. In most patients, sedation decreases or disappears entirely with time, but until then patients taking trazodone should not perform hazardous activities requiring mental alertness or coordination, including driving and similar activities. The sedative effect is increased when trazodone is taken with other central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines. It may be dangerous to take trazodone in combination with these substances.

Although lower in anticholinergic side effects than tricyclic antidepressants, trazodone should be used cautiously and with close physician supervision in people, especially the elderly, who have benign prostatic hypertrophy, urinary retention, and glaucoma, especially angle-closure glaucoma (the most severe form). Before starting treatment, people with these conditions should discuss the relative risks and benefits of treatment with their doctors to help determine if protriptyline is the right antidepressant for them.

Trazodone may increase heart rate and stress on the heart. It may be dangerous for people with cardiovascular disease, especially those who have recently had a heart attack, to take this drug. In rare cases where patients with cardiovascular disease must take trazodone, they should be monitored closely for cardiac rhythm disturbances and signs of cardiac stress or damage.

Side effects

Trazodone shares side effects common to many antidepressants. The most frequent of these are dry mouth, constipation, and urinary retention, though these are less common than with tricyclic antidepressants. Increased heart rate, sedation, irritability, dizziness, and decreased coordination can also occur. As with most side effects associated with antidepressants, the intensity is highest at the beginning of therapy and tends to decrease with continued use.

Dry mouth, if severe to the point of causing difficulty in speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug. Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief.

Men with prostate enlargement who take trazodone may be especially likely to have problems with urinary retention. Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine. In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant. In extreme cases, patients may require treatment with bethanechol, a drug that reverses this particular side effect. In rare cases, trazodone has also been known to cause priapism, a prolonged and painful penile erection. People who think they may be experiencing any side effects from this or any other medication should tell their physicians.

Interactions

Because both trazodone and members of the class of antidepressants known as monoamine oxidase (MAO) inhibitors may increase serotonin levels in the brain, the combination of these drugs can lead to a condition known as serotonin syndrome. Symptoms of serotonin syndrome include a prolonged rapid heart rate, hypertension (high blood pressure), flushing of the skin, hallucinations , tremors, and hyperthermia (increased body temperature). Because of this, it can be dangerous to take trazodone in combination with MAO inhibitors such as Nardil ( phenelzine sulfate) or Parmate ( tranylcypromine sulfate). The same holds true when combining trazodone with a selective serotonin uptake inhibitor (SSRI) antidepressant such as Prozac (fluoxetine), paroxetine, or sertraline.

Trazodone may increase the blood pressure–lowering effects in patients who are taking antihypertensive medications. Patients who take these drugs together should have their blood pressure monitored regularly so that their antihypertensive medications can be adjusted if their blood pressure becomes too low.

The sedative effects of trazodone are increased by other central nervous system depressants such as alcohol, sedatives, sleeping medications, or medications used for other mental disorders such as schizophrenia . The anticholinergic effects of trazodone may be additive with other anticholinergic drugs such as benztropine , biperiden , trihexyphenidyl , and antihistamines.

See also Neurotransmitters

Resources

BOOKS

American Society of Health-System Pharmacists. AHFS Drug Information 2002. Bethesda: American Society of Health-System Pharmacists, 2002.

DeVane, C. Lindsay, Pharm.D. "Drug Therapy for Mood Disorders." In Fundamentals of Monitoring Psychoactive Drug Therapy. Baltimore: Williams & Wilkins, 1990.

Jack Raber, Pharm.D.