Trazodone: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on April 4, 2023.

1. How it works

• Trazodone is an antidepressant that may also be used to treat insomnia.
• Experts aren't sure exactly how trazodone works but suggest it improves the symptoms of depression by inhibiting the uptake of serotonin by nerves in the brain. This increases levels of serotonin in the nerve synapse (the space between two nerves).
• Trazodone has a unique chemical structure and is unrelated to selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), or monoamine oxidase inhibitors (MAO inhibitors). It is structurally related to nefazodone. Trazodone and nefazodone belong to the class of drugs known as serotonin modulators. It may also be called a serotonin receptor antagonists and reuptake inhibitor (SARI).

2. Upsides

• Effective for the treatment of major depressive disorder (MDD).
• May be used “off-label” for insomnia (problems with sleeping) in adults. Off-label means the use is not FDA-approved, but may be an acceptable use.
• Has not been associated with drug-seeking behavior.
• Not classified as a controlled substance.
• Generic trazodone is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Dry mouth, headache, constipation, diarrhea, and sexual dysfunction.
• Trazodone may cause a discontinuation syndrome if abruptly stopped, symptoms include anxiety, agitation, and sleep disturbances. When the time comes to withdraw trazodone, the dosage should be tapered off slowly under a doctor's advice.
• May increase the risk of suicidal thoughts or behavior in young adults, children, and teenagers within the first months of treatment (similar to other antidepressants).
• May cause drowsiness or dizziness and affect a person's ability to drive or operate machinery. Alcohol should be avoided.
• Hyponatremia and low blood pressure (particularly when going from a sitting to a standing position) may occur. Rarely, may cause ECG changes in the heart (particularly in those with pre-existing cardiac disease) and priapism (painful erections lasting more than 6 hours in duration).
• May precipitate a manic episode in people with undiagnosed bipolar disorder.
• Interaction or overdosage may cause serotonin syndrome (symptoms include mental status changes [such as agitation, hallucinations, coma, delirium]), fast heart rate, dizziness, flushing, muscle tremor or rigidity, and stomach symptoms (including nausea, vomiting, and diarrhea).
• May increase the risk of bleeding, especially if used with other drugs that also increase bleeding risk. May trigger an angle-closure attack in certain people at risk of this type of glaucoma.
• May cause a lowering of total body sodium (called hyponatremia); elderly people or people taking diuretics or already dehydrated may be more at risk.
• Rarely causes seizures.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Trazodone is mostly used for its sleep-inducing effects (an off-label indication) rather than as an antidepressant. Only generic forms are available which makes it a lot cheaper than some other sleep-inducing alternatives, and it is not classified as a controlled substance. However, it may cause withdrawal symptoms on discontinuation.

5. Tips

• Take immediate-acting tablets shortly after a meal or light snack. If approved by your doctor, it may help to take the majority of your dosage at bedtime to limit the side effect of drowsiness.
• Slow-release tablets should be taken at the same time every day in the late evening, preferably at bedtime, on an empty stomach. The tablets should be swallowed whole unless only half a dose is needed and then they should be broken along the scoreline. Do not chew or crush slow-release tablets.
• Your doctor may start you on a lower dosage of trazodone and titrate the dosage up slowly to minimize the risk of developing side effects. Follow his or her instructions.
• Do not stop trazodone suddenly as withdrawal symptoms may occur. Slow dosage reduction over weeks to months is recommended.
• Families and caregivers should monitor patients for worsening depression or suicidal thoughts, particularly during the first few months of therapy, and communicate concerns with the prescriber. Also, monitor for symptoms of serotonin syndrome (agitation, confusion, fast heart rate, muscle rigidity or twitching, heavy sweating, diarrhea).
• Trazodone hydrochloride tablets should not be used within 14 days of a monoamine oxidase inhibitor (MAOI) drug.
• Have your pharmacist check for drug interactions.
• Report any fever, sore throat (or other signs of infection) to a doctor.

6. Response and effectiveness

• Peak concentrations are reached within 1 hour if taken on an empty stomach or 2 hours if taken with food.
• In clinical studies, approximately 75% of patients saw an improvement in symptoms of depression by the second week of treatment; however, some patients may require at least four weeks for the full effects of trazodone to be noticed.

7. Interactions

Medicines that interact with trazodone may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with trazodone. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with trazodone include:

• anticonvulsants, such as fosphenytoin, phenytoin, phenobarbital, or primidone
• antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
• any medication that may cause drowsiness, such as benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as codeine, morphine)
• lithium
• other antidepressants, such as tricyclic antidepressants (eg, amitriptyline), monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine), and SSRIs (eg, paroxetine, sertraline)
• other medications that affect serotonin, such as amphetamines, fentanyl, lithium, tramadol, triptans (eg, almotriptan, eletriptan, or sumatriptan), or St. John's Wort
• other medications that are metabolized by the same enzymes (CYP3A4) such as cyclosporin, erythromycin, ketoconazole
• warfarin.

Avoid drinking alcohol or taking illegal or recreational drugs while taking trazodone.

Note that this list is not all-inclusive and includes only common medications that may interact with trazodone You should refer to the prescribing information for trazodone for a complete list of interactions.

References

• Trazodone. Revised 03/2023. Pharmasource Meds, LLC. https://www.drugs.com/pro/trazodone.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Trazodone only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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