The P-I-E-N-O Parkinsn's List Drug Database
trazodone / DesyrelTM
ANTIDEPRESSANT:
Tricyclic : MODERATE RISK
Description: Trazodone is an oral antidepressant, unrelated to other known antidepressants. It possesses some similarities of action to other antidepressant drugs, however, and also has some action as an anxiolytic. Trazodone is used in the treatment of major depression, generalized anxiety disorderý, and insomniaý. Trazodone was approved by the FDA in 1981.
Mechanism of Action: Similar to fluoxetine, trazodone inhibits the reuptake of serotonin, although trazodone is less potent than fluoxetine in this regard. Trazodone appears to act as a serotonin agonist at higher doses (6-8 mg/kg), yet appears to antagonize serotonin at low doses (0.05-1 mg/kg). Antidepressant activity is believed to be produced by blocking the reuptake of serotonin at the presynaptic neuronal membrane. Long-term therapy also can affect postsynaptic neuronal receptor binding sites. Trazodone has no influence on the reuptake of norepinephrine or dopamine within the CNS. There is some evidence in animals that norepinephrine release is enhanced by trazodone. Trazodone does not inhibit monoamine oxidase.
Anticholinergic activity is lower with trazodone than with the tricyclic antidepressants. It has a sedative effect, which is believed to be produced by the ›-adrenergic blocking action and modest histamine blockade. Total sleep time is increased, but unlike the tricyclics, trazodone does not affect stage 4 sleep. Trazodone has weak skeletal muscle-relaxant activity and no anticonvulsant activity. Unlike the tricyclics, trazodone has no direct quinidine-like action on the cardiovascular system. Hypotension may be a result of lowered arterial blood pressure caused by the blocking of pressor response to norepinephrine. Trazodone may affect the endocrine system, but results are inconclusive.
Pharmacokinetics: Trazodone is administered orally and is well absorbed from the gut. Food affects absorption; when taken with or shortly after a meal, there is about a 20% increase in the amount of drug absorbed, a decrease in peak plasma concentration, and a delay in the time taken to reach peak concentration. Peak levels are achieved 1 hour after dosing in the fasting state and 2 hours after dosing with food. There is wide individual response. Most patients who respond to therapy with trazodone do so by the end of the second week of therapy. The drug is highly protein-bound. Studies on distribution in humans are incomplete, but in animals, the drug is distributed mainly into liver, kidneys, small intestine, lungs, adrenal glands, and pancreas, and is shown to cross the blood-brain barrier. Trazodone is excreted into breast milk.
Metabolism in the liver is extensive. None of the metabolites is believed to be pharmacologically active. There is wide individual variation in clearance, which appears to take place in a biphasic manner. The time of the first phase is 3-6 hours and the second phase 5-9 hours. Drug accumulation in plasma can occur in some patients. Elimination is mainly through the urine, with about 75% of a dose being excreted, mainly as metabolites, within 72 hours. About 20% is excreted via the bile in the feces.
CONTRAINDICATIONS/PRECAUTIONS: Trazodone should be used with caution in patients with cardiac disease because arrhythmias could occur in these patients, even though trazodone has limited arrhythmogenic potential. Trazodone should not be used during the acute recovery period following myocardial infarction.
Trazodone should be used with caution in patients with hepatic disease because the drug could accumulate and adverse reactions could increase.
Trazodone and its metabolites are excreted primarily in the urine and should be used with caution in patients with renal impairment because of possible reduced excretion and increased effects of the drug.
All effective antidepressants can transform depression into mania in predisposed individuals (e.g., bipolar disorder). The usual presentation of this switch is the sudden appearance of insomnia. The antidepressant should be held and appropriate therapy to treat the manic symptoms initiated. Therapeutic doses of lithium (and possibly carbamazepine or valproate) are effective in suppressing the switch process.
All antidepressants should be used with caution in depressed patients because of the possibility of suicidal ideation. Close monitoring of the patient is essential during the initial stages of therapy and trazadone prescribed in the smallest quantity consistent with good management.
The elderly generally require a lower dosage schedule and are more susceptible to adverse reactions. If the elderly patient is unable to take an SSRI antidepressant, however, trazodone may be preferred over a tricyclic antidepressant because of the lower incidence of cardiac effects.
Trazodone causes sedation and should be used with caution in patients with alcoholism. The sedative effects of alcohol can be additive to trazodone's effects.
Trazodone is classified as FDA pregnancy category C. Adequate studies have not been done in humans and benefits versus risks should be considered. Trazodone is excreted into the breast milk. Although no problems have been documented during breast-feeding, the benefits and risks should be taken into account.
DRUG INTERACTIONS: Monoamine oxidase inhibitors (MAOIs), such as furazolidone, isocarboxazid, pargyline, phenelzine, procarbazine, selegiline, or tranylcypromine) used concurrently with trazodone can cause hyperpyrexia, hypertension, or seizures. An interval of 14 days is recommended between cessation of an irreversible MAOI agent and initiation of trazodone therapy.
Guanabenz can lead to increased circulation of catecholamines. Concomitant use of trazodone could lead to hypertension, especially during the second week of antidepressant therapy. Occasionally, the hypertension will occur within the first few days of tricyclic antidepressant therapy.
Ethanol or CNS depressants should be used with caution in combination with trazodone because of additive CNS-depressant effects and possible respiratory depression or hypotension. Barbiturates and carbamazepine induce hepatic microsomal enzymes and increase the metabolism of trazodone.
Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, sertraline, paroxetine, and fluvoxamine, are another class of antidepressants that have been reported to cause symptoms of tricyclic antidepressant toxicity when used together. The mechanism of this interaction is poorly understood, but it is believed to involve specific isoenzymes of the cytochrome P-450 mixed-function oxidase system. The most critical and well-studied pathway is 2D6. CYP2D6 (cytochrome P-450 2D6) is impaired most by fluoxetine and least by sertraline. Trazodone's interaction has not been clearly elucidated at this time. Patients receiving an SSRI and trazodone should be monitored closely for excessive adverse effects from either agent.
Trazodone can lower the seizure threshold. Patients may require increased concentrations of anticonvulsants to achieve equivalent effects if trazodone is added.
Trazodone metabolism can be inhibited by cimetidine or ranitidine, resulting in increased plasma levels of trazodone that could lead to toxicity. Patients should be closely observed for toxic effects such as orthostatic hypotension or sedation.
Trazodone may have an increased risk of causing toxicity if used with oral contraceptives, fluoxetine, erythromycin, or methylphenidate because of the inhibition of hepatic metabolism.
Trazodone used concomitantly with thyroid hormones can increase therapeutic and toxic effects (such as arrhythmias and CNS stimulation) of both medicines.
ADVERSE REACTIONS: Priapism (including clitoral priapism) has been reported in a number of patients receiving trazodone. Priapism occasionally results in permanent impairment of erectile function or impotence. Patients should be warned of the possibility and to discontinue the drug at once and consult with the physician if this reaction occurs. Careful consideration should be given before administering the drug to postpubescent male patients. Other sexual abnormalities include ejaculation dysfunction (retrograde or no ejaculation), orgasm dysfunction (anorgasmia), and libido increase.
Hypotension, including orthostatic hypotension, can occur during therapy with trazodone and is dose-related. Patients taking antihypertensive drugs may require a reduction in the dosage.
Cardiac arrhythmias, eg. ventricular tachycardia, are not as common during therapy with trazodone as with tricyclic antidepressants, but they have occurred in patients with or without preexisting cardiac disease. Various ECG changes have been noted during therapy with trazodone.
Drowsiness is one of the most common side effects of trazodone. Because of other CNS effects, such as dizziness, lightheadedness, nervousness, fatigue, and headache, caution should be exercised in the undertaking of tasks requiring mental alertness until the effects of the drug are known. Some CNS side effects occur during the first few weeks of therapy, and tolerance can develop after 1 or 2 weeks.
Muscle tremor and musculoskeletal aches and pains have been reported during therapy with trazodone, which may due to weak skeletal muscle-relaxant activity.
Xerostomia is a common side effect during therapy with trazodone and is believed to be due to ›A-adrenergic blocking effects rather than to anticholinergic action.
Blurred vision during therapy with trazodone may be an anticholinergic effect. Patients experiencing ocular changes should have an ophthalmological examination.
Nausea/vomiting, along with other manifestations of GI upset, can be reduced by administering trazodone with food, which reduces the absorption rate.
PATIENT INFORMATION:
What do trazodone tablets do?
Trazodone (DesyrelTM ) is an antidepressant, a medicine that helps to lift mental depression. Trazodone is chemically different from other antidepressants. It can help patients whose depression has not responded to other medications, or who have experienced limiting side effects with other antidepressants. Generic trazodone tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take trazodone?
They need to know if you have any of these conditions:
How should I take this medicine?
Take trazodone tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take trazodone shortly after a meal or a light snack. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking the tablets except on your doctor's advice.
Special precautions for use in children:
This medicine is not for children under 18 years old.
Elderly patients over 65 years old may have a stronger reaction to this medicine and need smaller doses.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is less than four hours to your next dose, take only that dose and skip the missed dose. Do not take double or extra doses.
What other medicines can interact with trazodone?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking trazodone?
Serious side effects with trazodone include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with trazodone include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take trazodone?
Visit your doctor for regular checks on your progress. You may have to take trazodone for two weeks or more before you feel better. If you have been taking trazodone for some time, do not suddenly stop taking it. Your doctor may want you to gradually reduce the dose; ask for advice.
You may get drowsy, dizzy or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how trazodone affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol may increase dizziness or drowsiness; avoid alcoholic drinks.
Trazodone can make your mouth dry. Chewing sugarless gum, sucking hard candy and drinking plenty of water will help.
Do not treat yourself for coughs, colds, or allergies without asking your doctor or pharmacist for advice. Some ingredients may increase possible side effects.
If you are going to have surgery, tell your doctor or dentist that you are taking trazodone.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature, approximately 25C (77F). Avoid temperatures above 40C (104F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.
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