Section 3.2.2.2

Trazodone

General Description

Trazodone (Desyrel) is a triazolopyridine derivative that is used primarily for the treatment of depression. Trazodone shares the triazolo ring structure with alprazolam (Xanax), a benzodiazepine with possible antidepressant effects.

Trazodone is structurally unrelated to the tricyclic antidepressants, tetracyclic anti-depressants, and monamine oxidase inhibitors (MAOIs). Trazodone differs from those other antidepressants in having almost no anticholinergic adverse effects.

Indications for Medication

The primary indication for the use of trazodone is major depression. Trazodone is as effective as standard antidepressants in the short-term and long-term treatment of major depression.

Trazodone is particularly effective at improving sleep quality. Trazodone increases total sleep time, decreases the number and duration of nighttime awakenings, and decreases the amount of rapid eye movement. Unlike tricyclic antidepressants, trazodone does not decrease stage 4 sleep.

Trazodone may be useful for the treatment of depression associated with marked anxiety symptoms. Trazodone may also be useful for controlling severe agitation in elderly patients. In low doses, trazodone can be used as a hypnotic.

Clinical Guidelines

The usual starting dose for trazodone is 50mg taken orally the first day. The dose can be increased to 50mg taken orally twice daily on the second day; and the dose may be possibly increased to 50mg taken orally three times a day on the third or fourth day - if there are no problems with sedation or orthostatic hypotension.

The therapeutic range for trazodone is 150-600 mg a day in divided doses. Some studies report that dosages of 400-600 mg a day are required for maximum effect. Other studies suggest that a 300-400 mg a day dose is usually sufficient. The dose may need to be titrated to 300 mg, and then re-evaluated for dose increases based on the clinical response.

Adverse Effects

The most common adverse effects associated with trazodone are sedation, orthostatic hypotension, dizziness, headache, and nausea. Trazodone may cause dry mouth and gastric irritation. But trazodone is not associated with the usual anticholinergic side effects such as urinary retention and constipation.

Trazodone should be taken with food, as the systemic absorption of this medication increases by 20% when taken with food.

Trazodone is associated with the rare occurrence of priapism, the symptoms of prolonged erection in the absence of sexual stimuli. Patients should be advised to report if erections are gradually becoming more frequent or prolonged. In such cases, the clinician should consider another antidepressant. Untreated priapism can lead to gangrene of the penis.

Trazodone is safe in the suicidal patient. There have been no reported fatalities from trazodone overdose when the drug was taken alone. Symptoms of trazodone overdose include loss of muscle coordination, nausea, vomiting and drowsiness. Overdose fatalities can occur if trazodone is taken with other drugs.

The use of trazodone is contraindicated in pregnant women. Trazodone passes into breast milk. Trazodone should not be used with nursing mothers.

Drug-Drug Interactions

Fluoxetine raises trazodone blood levels. But trazodone has been useful in the treatment of fluoxetine induced insomnia. In these patients, trazodone should be used at a low dose of 50-100mg at bedtime.

Trazodone potentiates the central nervous system depressant effects of other centrally acting drugs and alcohol. This is especially problematic if there is any respiratory impairment.

The concurrent use of trazodone and antihypertensives may cause hypotension. Trazodone should also not be used with MAOIs. At least two weeks should elapse before starting trazodone after the discontinuation of the MAOI.

The consent form for this medication is "Antidepressant (Anti-Obsessive-Compulsive Medication / Tricyclics & Similarly Acting Medications)."