Trazodone is a prescription antidepressant medication for adults and works as a serotonin antagonist and reuptake inhibitor (SARIs). This medication is used to treat depressive disorder and anxiety. Tell your doctor if you have suicidal or self-harming thoughts, as they may increase when starting treatment, which usually takes at least two weeks to work.

Trazodone brand names

Trazodone is sold under the following brand names: 

  • Desyrel
  • Desyrel Dividose
  • Oleptro
  • Molipaxin
  • Trialodine

What is trazodone prescribed for?

Trazodone is prescribed to treat:

This drug is used to improve energy level, appetite and mood and to decrease insomnia and anxiety related to that psychiatric disorder.

Your healthcare provider may prescribe trazodone to treat insomnia and schizophrenia, control movements caused by the side effects of other medications, and to treat alcoholism. [1]

You should never take trazodone without proper medical advice or supervision.

How does trazodone work?

Trazodone belongs to a group of medicaments called serotonin receptor antagonists and reuptake inhibitors (SARIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance, which is necessary for nerve cells and the brain to function properly.

Trazodone is a triazolopyridine derivative that inhibits the reuptake of serotonin by the neuronal presynaptic membrane. Unlike other antidepressants, this drug has no effect on the reuptake of norepinephrine or dopamine in the central nervous system. Therefore, it does not enhance the cognitive and affective functions modulated by these neurotransmitters, norepinephrine and dopamine, such as increased alertness, anticipation, perseverance or motivation. This results in sedative and hypnotic effects typical of this drug and is believed to be produced by an alpha-adrenergic blockade and a histamine blockade. [2]

How is trazodone usually taken?

You should follow your doctor or pharmacists instructions for administering this medicine. If you have any doubts, you should consult your doctor or pharmacist again. [3]

  • Trazodone is a medicine to be taken orally with water.
  • Takingit after each meal is advisable to reduce possible side effects.
  • If your doctor has instructed you to take trazodone once daily, you should take it before going to bed.
  • Ask your doctor if you feel the medicine’s effectis too weak or too strong. Under no circumstances change the prescribed dose yourself.

For the treatment of depression and/or generalized anxiety disorder:

In adults, the recommended starting dose of trazodone is 50-100 mg/day. The dose can be increased by 50 mg/day every 3-4 days, up to 300 mg/day, as needed. In the case of taking the divided dose before each meal, the larger portion should be taken before bedtime.

  • In the case of hospitalized patients, the dose can be increased up to 600 mg/dayin divided doses.
  • In elderly patients over 65 years of age and debilitated patients, treatment should be initiated with divided doses of 50-100 mg/day after meals or with single doses before bedtime. The dose may be increased depending on the clinical response observed in the patient.
  • In patients with hepatic insufficiency, caution should be taken when prescribing. Trazodone is metabolized mainly by the liver and may cause hepatotoxicity. Therefore, yourhealthcare provider should perform periodic liver function tests to avoid
  • It is unnecessary for patients with kidney failure to adjust the dose without severe renal insufficiency.

Trazodone is an antidepressant, but it does not cure depression or anxiety. Instead, it only minimizes its symptoms. Its beneficial effect will begin to be felt two weeks after starting treatment. Trazodone should be continued for the time indicated by the doctor, even if the patient feels well.

For the treatment of insomnia in adults, the recommended dose is 50mg before bedtime. 

For treating alcohol use disorder in adults, a dose of 50-100mg once a day is recommended.

Each oral tablet usually contains 100 mg of trazodone hydrochloride and can be divided into equal doses of 50mg. In this way, the physician can increase or decrease the dose gradually.

How long does trazodone stay in your system?

Trazodone is mainly eliminated through urine, excreting about 75% of the dose within 72 hours. About 20% is excreted via the biliary route in the feces. [4]

Trazodone has a two-phase elimination. The first phase has a half-life of about 1 hour and about 8 hours for the second phase. Thus, the drug has a terminal elimination half-life of 5 to 13 hours.

The drug is distributed mainly in the liver and, to a lesser extent, in the kidneys, small intestine, lungs, adrenal glands and pancreas, and can cross the blood-brain barrier. Trazodone can also be excreted in breast milk.

Trazodone side effects

Trazodone may cause side effects, although not all people experience them. Inform your doctor if these symptoms are severe or persistent: [5]

  • Drowsiness or tiredness
  • Feeling low energy
  • General discomfort
  • Nausea, vomiting or indigestion
  • Constipation, diarrhea
  • Dry mouth, altered taste, increased saliva, nasal congestion
  • Increased sweating
  • Dizziness, headache, confusion, weakness, tremors
  • Blurred vision
  • Loss of appetite, weight loss
  • Difficulty sleeping
  • Fluid retention in arms or legs
  • Skin rash, itching
  • Chest pain
  • Pain in the extremities, back pain, pain in the muscles, pain in the joints
  • Involuntary muscle movements
  • High fever, intense chills, sore throat or mouth ulcers
  • Anxiety, nervousness, agitation
  • Manias, delirium, memory disorders
  • Nightmares
  • Decreased sexual desire
  • Dizziness
  • Loss of coordination
  • Increased blood pressure
  • Difficulty in speaking
  • Alterations in blood tests with a decrease in blood cells, an increase in liver enzymes and a decrease in sodium

If you experience any of the following effects, you should stop taking trazodone and see your doctor immediately:

  • Swelling of the hands, feet, ankles, face, lips or throat, itchingskin and hives
  • Suffering from priapism, which is a painful erection of the penis that does not go away
  • Yellowing of the skin or eyes
  • Increased infections
  • Frequent bruising
  • Swelling and pain in the abdomen, vomiting and constipation

If you notice the following serious side effects, seek medical attention immediately:

  • Self-harming or suicidal thoughts
  • Tiredness, weakness, dizziness, loss of skin color
  • Convulsions or seizures
  • Numbness, prickling, burning or tingling of the skin
  • Confusion, restlessness, sweating, shaking, shivering, hallucinations, muscle twitching and rapid heartbeat
  • Shortness of breath, difficulty walking and uncontrollable muscle spasms, accompanied by a fever above 38ºC (100.4ºF)
  • Cardiac arrhythmias

This list does not mention all side effects. If you experience any type of side effect, consult your doctor. [6]

Trazodone precautions

Before taking trazodone:

  • Tell your doctor and pharmacist if you are allergic to this medicine, any other medicines,or any allergies in general, as serious but rare allergic reactions can occur.
  • Tell your doctor if you are taking any medications, vitamins, herbal products, or nutritional supplements, if you have stopped taking them within the past 14 days, or if you plan to take them.
  • Tell your doctor or pharmacist your personal and family medical history, especially of heart disease, suicidal thoughts, bipolar disorder, epilepsy, kidney or liver disease, high blood pressure, glaucoma, leukemia or myeloma, among other conditions.

Trazodone can be excreted through breast milk, so you should tell your doctor if you are pregnant, plan to become pregnant or are breast-feeding. [7]

It is also important to tell your doctor if you have surgery, including dental surgery.

Trazodone may cause dizziness, so you should avoid performing potentially dangerous tasks, such as driving or operating machinery, until you understand how this medicine affects you.

The use of alcohol or cannabis may increase the adverse effects of trazodone, especially those related to psychomotor disturbances.

Trazodone interactions

Several drugs can interfere with the beneficial effects of trazodone. Some of them are listed below. Please inform your doctor if you are taking other medications: [8]

  • Anticonvulsants (carbamazepine, phenytoin): decreasetrazodone’s beneficial effect as its hepatic metabolism is enhanced.
  • Non-selective monoamine oxidase inhibitors (MAOIs), such as the antibiotic linezolid, may increase adverse effects related to serotonin levels.
  • Central nervous system depressants (such as barbiturates, musculoskeletal relaxants, anxiolytics, sedatives, benzodiazepines, entacapone, ethanol, general anesthetics, some H1 blockers, hypnotics) may affect patients using trazodone because of their additive effects.
  • The use of antihypertensive drugs can potentiate extreme hypotension. As a result, your doctor should monitor doses to avoid this effect.
  • Anticoagulants, such as warfarin, may have their effect diminished due to the action of trazodone.
  • Digoxin potentiates the possible side effects of trazodone.
  • Antipsychotics (chlorpromazine, thioridazine, trifluoperazine) increase the hepatotoxic effect of the drug.
  • Fluoxetine and haloperidol inhibit their hepatic metabolism increasing their toxicity.
  • Levodopa and other tricyclic antidepressants can increase the toxicity of trazodone, asit affects the levels of vasopressor neurotransmitters. In addition, since these drugs increase serotonin levels, they can produce excessive serotonergic stimulation.  

Trazodone storage

The medicine should be stored in a shaded (below 86 F), cool and dry place. It must be kept in its original container and out of sight and reach of children.

Ask your pharmacist for proper handing to dispose of leftover or expired medicines. Doing so will avoid risks to public health and the environment. 

What to do if you overdose on trazodone

In case of an overdose, consult your doctor or pharmacist immediately or go to the nearest hospital.

The most common side effects of excessive ingestion are general malaise, dizziness, drowsiness, convulsions, confusion, arrhythmias, breathing difficulties or painful erections that do not subside.  

Frequently asked questions about trazodone

How long does trazodone take to work?

The beneficial effects of trazodone usually appear two weeks after the first intake. However, it is important to remember that symptoms related to depression and/or anxiety may increase slightly during the first days of its use.

Is trazodone habit forming?

Antidepressants do not produce dependence, but it is advisable to reduce the dose gradually when treatment ends to avoid a rebound effect, mainly related to insomnia.

Trazodone vs. mirtazapine: What’s the difference?

Both prescription drugs belong to the group of sedative antidepressants.

One of the main differences between the two drugs is the dosage used. The dose of mirtazapine is usually quite a bit lower, at 15 to 45 mg per day, while the dose used with trazodone is usually 50 to 400 mg per day. In addition, while both drugs are used to treat depression, anxiety and insomnia, mirtazapine is also prescribed to treat generalized anxiety and post-traumatic stress disorder.   

Regarding its mechanism of action, mirtazapine has a dual antidepressant effect, as it potentiates the neurotransmitters serotonin and noradrenaline. In contrast, trazodone only acts at the serotonin level. Another effect of this difference in the mechanism of action is that while mirtazapine induces an increase in appetite and weight gain, trazodone does not.

Both antidepressant drugs produce drowsiness, so it is convenient to take them at night. In the case of mirtazapine, this effect does not increase when the dose is increased, but in trazodone, it does. Therefore, when treating insomnia with trazodone, it is important to increase the dose gradually according to the patient’s response.

Although neither drug produces severe sexual dysfunction, as with other antidepressants, trazodone has the lesser effect of the two concerning this adverse reaction.

Another important difference between trazodone and mirtazapine is the half-life of their antidepressant effect. Trazodone has a shorter half-life of 5 to 9 hours, while the half-life of mirtazapine in the body is 20 to 40 hours. This is why mirtazapine is usually taken in single doses and trazodone in at least three doses per day. Therefore, in treating insomnia, the use of trazodone is more effective since it can be limited to hours of sleep. [9]

Resources:

  1. Fagiolini A, Comandini A, Catena Dell'Osso M, Kasper S. (2012). Rediscovering Trazodone for the Treatment of Major Depressive Disorder. CNS Drugs, 26(12), 1033-104949. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693429/
  2. Schwasinger-Schmidt TE, Macaluso M. (2018). Other Antidepressants. Antidepressants, 325-355. https://pubmed.ncbi.nlm.nih.gov/30194544/
  3. Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. In: StatPearls. StatPearls Publishing, Treasure Island (FL); 2022  https://europepmc.org/article/med/32119293 
  4. Alcántara-López, M, Gutiérrez-García, A, Hernández Lozano, M, M. Contreras, C. (2009). Trazodone, an atypical antidepressant with anxiolytic and sedative properties. Archivos de Neurociencias. 14. 249-257. https://www.medigraphic.com/pdfs/arcneu/ane-2009/ane094g.pdf 
  5. Santos G, Moreira AM. (2017). Distressing Visual Hallucinations after Treatment with Trazodone. Case Reports in Psychiatry, 2017, 1-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494093/
  6. Smales ET, Edwards BA, Deyoung PN, McSharry DG, Wellman A, Velasquez A, Owens R, Orr JE, Malhotra A. (2015). Trazodone Effects on Obstructive Sleep Apnea and Non-REM Arousal Threshold. Annals of the American Thoracic Society, 12(5):758-764. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418332/
  7. Saito J, Ishii M, Mito A, Yakuwa N, Kawasaki H, Tachibana Y, Suzuki T, Yamatani A, Sago H, Murashima A. (2021). Trazodone Levels in Maternal Serum, Cord Blood, Breast Milk, and Neonatal Serum. Breastfeeding Medicine, 16(11):922-925. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8817729/
  8. Carvalhana S, Oliveira A, Ferreira P, Resende M, Perdigoto R, Barroso E. (2016). Acute Liver Failure due to Trazodone and Diazepam. GE - Portuguese Journal of Gastroenterology, 24(1):40-42. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553376/
  9. Davis R, Wilde MI. (1996). Mirtazapine. CNS Drugs, 5(5):389-402. https://pubmed.ncbi.nlm.nih.gov/26071050/