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Trazodone side effects

by egpat         5 Jun 2024

Trazodone is one of the antidepressants. This drug can be used for the treatment of major depressive disorder, where trazodone increases serotonin levels, thereby reducing the symptoms of depression. For the treatment of depression, this drug can be given at an initial dose of 150 mg, and the dose can be slowly increased based on the response of the drug.

In order to control the symptoms of depression, at least six months of treatment with trazodone are required. Since this drug is used for a longer period at a high dose for treating depression, side effects are also more pronounced with this drug, which should be carefully monitored. Apart from being used for the treatment of depression, trazodone can also be used for other conditions. This drug is indicated for the management of anxiety and can be given at a dose of 75 mg.

The use of trazodone produces some sleepiness in patients; that's why this drug can be used as an off-label sleeping aid for the treatment of insomnia. For this purpose, trazodone can be given at a dose range of 25 to 100 mg, where it can increase the sleepiness in the patients, and particularly, this drug can also reduce the insomnia that is commonly observed in depressive patients. For treating anxiety or insomnia, trazadone should be started at a low dose. However, in the treatment of depression, the dose may be slowly increased, which may result in significant side effects.

1. Sedation

Trazodone acts on the CNS, where it can increase serotonin levels, thereby elevating the mood in patients. But at the same time, it can also increase sleepiness, leading to sedation, somnolence, and drowsiness in the patients. This is particularly important when this trazodone is combined with other drugs or foods that again produce CNS depression. When trazodone is combined with alcohol, the CNS depressant activity is further increased. That's why it should not be combined with alcohol.

2. Dizziness

As trazodone produces sedation, it can increase drowsiness, which may result in lightheadedness and dizziness in the patient. These effects of trazodone may impair the daytime activities of the patient. So while using trazodone, care should be taken while working with machinery or driving vehicles, as this drug may impair the performance of the patients. Apart from these side effects, trazodone can also increase confusion, which is more troublesome for older people.

3. Effect on the eye

Apart from increasing serotonin levels, trazodone can block adrenergic and cholinergic receptors. Because of these effects, trazodone can increase pupillary dilatation, which may result in increased intraocular pressure in a few of the patients with narrow angles. Trazodone can precipitate acute angle closure glaucoma, so in such patients, care should be taken because this drug may increase the risk of further angle closure and raise the intraocular pressure. But in normal people, trazodone can produce some double vision or blurred vision because of anticholinergic side effects as well as pupillary dilatation. Therefore, while taking trazodone, either double vision or blurred vision can be commonly observed.

4. Prolongation of the QT interval

Just like many of the antidepressants, trazodone can also affect the cardiovascular system. This drug, particularly at high doses, can produce some cardiac arrhythmia. When this drug is used at a dose greater than 100 milligrams, there may be a greater risk for QT interval prolongation within the ECG.

Elevation in the QTc interval can lead to the development of cardiac arrhythmias, and it can even precipitate one of the conditions, torsades de pointes, which is a fatal cardiac arrhythmia that can be associated with an increase in the QT interval. So care should be taken when this trazodone is given to patients with pre-existing cardiac arrhythmias.

Even with a few drugs like itracanazole and clarithromycin, precautions should be taken because these drugs can block the metabolism of trazodone by inhibiting cytochrome P450 3A4 (CYP3A4) activity. When this enzyme is inhibited by these drugs, trazodone is not significantly metabolized, leading to increased levels in the plasma. This increases the risk of a prolonged QT interval.

Similarly, a few of the drugs, like class Ia antiarrhythmic agents and class III antiarrhythmic agents, can directly increase the QT interval within the ECG, so when they are combined with trazodone, they can precipitate fatal cardiac arrhythmias. So these drugs should be carefully combined with trazodone, and the dosage adjustment should be done in order to avoid prolongation in the QT interval.

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5. Orthostatic hypotension

Use of trazodone can affect the blood pressure in patients; it can reduce the blood pressure, which often changes with a change in position. Trazodone can produce orthostatic hypotension, resulting in syncope and fainting. Therefore, while taking trazodone, care should be taken, particularly when they change the posture, either from the lying position to the sitting position or from the lying position to the standing position. A sudden fall in blood pressure is observed due to the vasodilatory effects of trazodone. When the blood pressure is not improved, it results in a falling sensation and syncope in the patient.

6. Peripheral edema

This is another effect of trazodone on the blood vessels. It can block 5-HT2 receptors as well as alpha-1 receptors, which are located on the blood vessels. By blocking these receptors, it can increase vascular permeability, leading to increased vasodilatation and peripheral edema. So with prolonged use of trazodone, peripheral edema can be observed, resulting in the swelling of the legs, which is commonly observed at high doses of trazodone.

7. Dry mouth

This is another effect of trazodone, again commonly observed in most people. This drug can block cholinergic receptors, thereby reducing the action of acetylcholine within the CNS. Because of its reduced cholinergic action, trazodone can produce a set of anticholinergic side effects. Among them, dry mouth is one of the important side effects that is clearly observed in most of the patients. Repeated intake of water or chewing non-sugar candy pills or gum may help reduce dry mouth and increase saliva secretion.

8. Serotonin syndrome

Just like many of the antidepressants, trazodone can also increase serotonin levels in the brain. Therefore, it can precipitate one of the conditions, serotonin syndrome. This syndrome can be identified by a group of side effects in the patient. Any development of hyperthermia, a sudden rise in the body temperature, muscle rigidity, muscle spasm, or an increased heart rate resulting in tachycardia, confusion, fatigue, or tremors may indicate the development of serotonin syndrome. Particularly, this serotonin syndrome may develop when this trazodone is combined with other drugs that further increase the 5-HT levels.

9. Loss of sodium

Trazodone has some inhibitory activity on the anti-diuretic hormone (ADH). This can increase the excretion of sodium, thereby reducing the sodium levels in the serum and resulting in hyponatremia. This hyponatremia is more significant when sodium levels are less than 110 millimoles per liter. This can be observed when this trazodone is combined with drugs like diuretics, which further increase sodium excretion, thereby producing hyponatremia.

Such combinations can produce severe headaches and unexpected weakness, fatigue, and tremors in patients. So trazodone should be carefully combined with diuretics to prevent significant hyponatremia.

10. Prolonged erection

This effect of trazodone is observed in men. It can produce one of the conditions, priapism. With the use of trazodone, prolonged erection can be observed for more than six hours, resulting in painful erection. Practically, whenever this priapism is observed for more than four hours, care should be taken to prevent any damage to the erectile tissue.

11. Suicidal initiation

Just like many of the antidepressants, trazodone can also increase suicidal thoughts, which are more pronounced in adolescents as well as young patients. Even though trazodone can reduce the depressive symptoms and elevate the mood, at the same time, because of raised serotonin levels, it can also increase suicidal thoughts. Therefore, when this drug is prescribed to adolescent and young patients, close monitoring should be done to check for any development of suicidal initiation.


These are the 11 important side effects of trazodone, which is used as an anti-depressant for the treatment of major depressive disorder. This drug can also be used for the treatment of anxiety as well as to treat insomnia for off-label purposes. But whatever the clinical indication, trazodone can produce various side effects like sedation, somnolence, and sleepiness. It can also produce some dizziness and lightheadedness. Dry mouth is due to its anticholinergic side effects. Other side effects like orthostatic hypotension, peripheral edema, and an increasing QT interval are also observed.

In men, it can produce some prolonged erections, resulting in painful erections. It can also increase suicidal initiation in adolescents and young patients. However, when all these side effects are kept in mind and this drug is used at the lowest dose possible, it can be successfully used as an antidepressant and to control anxiety and insomnia.