medicationPrescription only (US)Trazodone is an approved medicine; the cited literature reports trial outcomes, not dosing advice.
TrazodoneBenefits, Dosage & Interactions
Also known as: Desyrel
Trazodone is an antidepressant medication that belongs to the class of serotonin antagonist and reuptake inhibitors (SARIs). It is primarily approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depressive disorder. It is typically taken in the evening.
Researched by DoseRoutine R&D TeamReviewed for accuracy by Nicholas Alexander, RSELast updated
Evidence: Strong — 171 human randomized trials and regulatory approval on file.
Evidence strengthStrong · 4/4
PreclinicalStrong human evidence
171 human randomized trials and regulatory approval on file.
Plasma half-life
Not established
Typical timing
bedtime
Default unit
mg
What published protocols report
Ranges documented in the literature, shown for reference. DoseRoutine does not recommend an amount — your prescriber or the product label sets the dose.
Reported for Trazodone in the cited sources. Published ranges are not dosing advice.
References & evidence
Documents the Trazodone entry is written from. Each number matches an inline marker above.
- [1]A Randomized-Controlled Trial Targeting Cognition in Early Alzheimer's Disease by Improving Sleep with Trazodone (REST)Eyob E, Shaw JS, Bakker A, et al. · J Alzheimers Dis · 2024 · Peer-reviewed · PMID 39422935
- [2]Effects of Trazodone on Sleep: A Systematic Review and Meta-analysisKokkali M, Pinioti E, Lappas AS, et al. · CNS Drugs · 2024 · Peer-reviewed · PMID 39123094
How to track Trazodone doses
Tracking Trazodone well takes four fields and a habit. Here is what to record so the log is still useful in three months.
- 1
Add the dose and unit
Log Trazodone with its dose in mg so totals stay comparable over time — including days when you split the dose or skip it.
- 2
Set the time of day and food rule
Typical timing is bedtime. Reminders fire at that time and can export to your calendar.
- 3
Check it against the rest of the stack
Run Trazodone through the interaction checker against everything else in the routine — supplements, peptides, hormones and prescriptions — before it becomes a daily habit.
- 4
Log adherence, not intentions
Mark each dose taken, skipped or delayed as it happens. Weeks of honest logs are what make an adherence rate or a trend line meaningful; retrospective guessing is not.
- 5
Review against outcomes
Review Trazodone alongside your logged metrics and any relevant blood work every few weeks before changing the dose, so the change is a response to data rather than to a good or bad day.
What to log each time
- Dose in mg
- Time of day
- Taken / skipped / delayed
- Any side effects or notable changes
References & Evidence
Sources on this page that document Trazodone dosing, timing and safety.
- [1]National Center for Biotechnology Information View source
Educational information only — not medical advice. Dose ranges vary by person, indication and prescriber.
What is Trazodone?Sources for this section: Jumps to this entry in the sources and references list at the end of the page.
Trazodone is an antidepressant medication that belongs to the class of serotonin antagonist and reuptake inhibitors (SARIs). It is primarily approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depressive disorder. Due to its significant sedative properties, trazodone is also frequently used off-label to help manage insomnia, particularly in individuals who experience difficulty falling or staying asleep (Source: FDA label, DrugBank).
Chemically, trazodone hydrochloride is a triazolopyridine derivative. Its effects are thought to be mediated through its interactions with various neurotransmitter systems in the brain. While beneficial for mood and sleep, it is important to understand its therapeutic profile, potential side effects, and interactions.
Individual responses to trazodone can vary, and its use should always be guided by a licensed healthcare professional. It is typically available in oral tablet form and is taken by mouth.
What does the research say about Trazodone?
Tap a section to expand.
Trazodone's therapeutic effects are multifactorial, primarily stemming from its interaction with serotonin receptors and its modest impact on serotonin reuptake (Source: DrugBank, PubChem).
* **Serotonin 5-HT2A Receptor Antagonism**: Trazodone is a potent antagonist at the 5-HT2A serotonin receptor. This action is believed to contribute to its antidepressant and anxiolytic (anxiety-reducing) effects, as blocking these receptors can enhance the activity of serotonin at other beneficial receptors (e.g., 5-HT1A).
* **Serotonin Reuptake Inhibition**: Trazodone weakly inhibits the reuptake of serotonin by neurons. This leads to an increase in the concentration of serotonin in the synaptic cleft, further contributing to its antidepressant properties.
* **Alpha-1 Adrenergic Receptor Antagonism**: Trazodone also acts as an antagonist at alpha-1 adrenergic receptors. This action is thought to contribute to its sedative effects and may be responsible for side effects like orthostatic hypotension (a drop in blood pressure upon standing).
* **Histamine H1 Receptor Antagonism**: The medication weakly blocks histamine H1 receptors, an action that further contributes to its sedative and hypnotic (sleep-inducing) effects.
Overall, the combination of these pharmacological actions, particularly its strong 5-HT2A antagonism and moderate serotonin reuptake inhibition, distinguishes trazodone from other antidepressants and explains its utility in both depression and insomnia.
Source for this section: Sources for How does Trazodone work?: Jumps to this entry in the sources and references list at the end of the page.
The primary benefits of trazodone largely center around its approved use for depression and its common off-label use for insomnia (Source: FDA label, Mayo Clinic).
* **Major Depressive Disorder**: Trazodone is effective in alleviating the symptoms of major depression, such as persistent sadness, loss of interest in activities, changes in appetite or sleep, feelings of worthlessness, and fatigue. Its antidepressant effects are thought to be related to its modulation of serotonin pathways in the brain.
* **Insomnia (Off-label)**: Due to its strong sedative properties, trazodone is widely prescribed off-label to help individuals who struggle with sleep. It can help reduce the time it takes to fall asleep (sleep latency) and improve sleep continuity, particularly in patients experiencing insomnia as a comorbidity with depression or anxiety. It is often considered for individuals for whom other sleep aids may be contraindicated or less effective.
* **Anxiety Symptoms**: While not a primary indication, trazodone's properties, particularly its serotonin modulation, can help reduce associated anxiety symptoms that often accompany depression.
It is important to note that while some individuals may experience benefits relatively quickly, the full antidepressant effects of trazodone may take several weeks to become apparent.
The efficacy of trazodone has been established through numerous clinical trials and widespread clinical use, supporting its role in treating depression and insomnia (Source: Cochrane, DrugBank).
For major depressive disorder, studies have consistently demonstrated that trazodone is effective in reducing depressive symptoms when compared to placebo. A review of antidepressant efficacy often includes trazodone, noting its distinct pharmacological profile and comparable efficacy to other antidepressants for moderate to severe depression (Source: Cochrane Reviews).
Regarding its off-label use for insomnia, evidence from multiple studies, including systematic reviews, indicates that trazodone can improve sleep parameters such as sleep onset latency and total sleep time in patients with chronic insomnia. One meta-analysis, for example, highlighted its effectiveness, especially at lower doses, for improving sleep efficiency and reducing nighttime awakenings, particularly in non-depressed individuals or those with co-occurring depression (Source: published meta-analyses in medical journals).
Furthermore, its mechanism of action, involving serotonin receptor modulation, is well-characterized and provides a strong theoretical basis for its observed clinical effects. While individual responses can vary, the overall body of evidence supports its utility in these therapeutic areas.
Like all medications, trazodone can cause side effects, though not everyone experiences them. The most common side effects are often related to its sedative properties (Source: FDA label, MedlinePlus).
Common side effects may include:
* Drowsiness or sedation
* Dizziness or lightheadedness
* Dry mouth
* Nausea, vomiting, or stomach upset
* Headache
* Blurred vision
* Constipation
More serious, but less common, side effects can occur:
* **Orthostatic Hypotension**: A significant drop in blood pressure upon standing, which can lead to fainting. This is particularly relevant in elderly patients.
* **Priapism**: A prolonged and painful erection, which is a rare but serious side effect requiring immediate medical attention.
* **Serotonin Syndrome**: A potentially life-threatening condition caused by too much serotonin in the brain, especially when taken with other serotonergic drugs. Symptoms include agitation, hallucinations, rapid heart rate, fever, sweating, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.
* **Cardiac Arrhythmias**: Trazodone may affect heart rhythm, especially in individuals with pre-existing heart conditions.
* **Increased Suicidal Thoughts**: Like other antidepressants, trazodone may increase the risk of suicidal thoughts or behavior, particularly in children, adolescents, and young adults (under 25) during the initial stages of treatment or when the dose is changed. This is an FDA black box warning.
Patients should report any concerning side effects to their healthcare provider promptly. This is educational information, not medical advice — consult a qualified clinician before starting, stopping or combining any compound.
Several warnings and precautions are associated with trazodone use to ensure patient safety (Source: FDA label, Mayo Clinic).
* **Suicidality Risk**: The FDA mandates a black box warning for all antidepressants, including trazodone, regarding an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults (ages 18-24) with major depressive disorder and other psychiatric disorders, especially during treatment initiation or dose changes. Close monitoring is essential.
* **Serotonin Syndrome**: The risk of serotonin syndrome increases when trazodone is co-administered with other serotonergic agents (e.g., SSRIs, SNRIs, MAOIs, triptans, tramadol, St. John's Wort). Symptoms require immediate medical attention.
* **Priapism Risk**: Though rare, priapism (prolonged, painful erection) is a serious warning. Patients, especially males, should be advised to seek immediate medical attention if an erection lasts longer than 4 hours.
* **Orthostatic Hypotension/Syncope**: Trazodone can cause significant drops in blood pressure upon standing, leading to dizziness or fainting, particularly at the start of treatment or with dose increases. Caution is advised, especially in elderly patients or those with cardiovascular disease.
* **Cardiac Effects**: Patients with pre-existing cardiac disease (e.g., angina, cardiac arrhythmias, recent myocardial infarction) should use trazodone with caution, as it has been associated with possible arrhythmias.
* **Hypersensitivity**: Allergic reactions to trazodone can occur.
* **Angle-Closure Glaucoma**: Trazodone may cause mydriasis (dilation of the pupil) which can trigger an acute angle-closure glaucoma attack in susceptible individuals.
* **Hyponatremia**: Low sodium levels in the blood have been reported with antidepressant use, particularly in elderly patients.
* **Withdrawal Symptoms**: Abrupt discontinuation of trazodone, especially after prolonged use, can lead to withdrawal symptoms such as anxiety, agitation, and sleep disturbances. Tapering the dose gradually is recommended under medical supervision.
This is educational information, not medical advice — consult a qualified clinician before starting, stopping or combining any compound.
Trazodone is contraindicated in certain situations where its use could pose significant risks (Source: FDA label, DrugBank).
* **Concomitant use with Monoamine Oxidase Inhibitors (MAOIs)**: Trazodone should not be used concurrently with or within 14 days of discontinuing an MAOI. This combination significantly increases the risk of serotonin syndrome, which can be life-threatening.
* **Hypersensitivity**: Individuals with a known hypersensitivity or allergic reaction to trazodone or any of its components should not use this medication.
* **Acute Recovery Phase of Myocardial Infarction**: Trazodone is generally not recommended in the acute recovery phase following a heart attack due to potential cardiac effects.
This is educational information, not medical advice — consult a qualified clinician before starting, stopping or combining any compound.
Mixing trazodone with certain other medications or substances can lead to dangerous interactions, including an increased risk of side effects or reduced efficacy (Source: FDA label, MedlinePlus).
* **Monoamine Oxidase Inhibitors (MAOIs)**: Concurrent use with MAOIs (e.g., phenelzine, tranylcypromine, selegiline) or within 14 days of stopping an MAOI is strictly contraindicated due to the high risk of serotonin syndrome.
* **Other Serotonergic Drugs**: Combining trazodone with other medications that increase serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), triptans (for migraines), linezolid, methylene blue, tramadol, St. John's Wort, or other antidepressants, can increase the risk of serotonin syndrome.
* **Central Nervous System (CNS) Depressants**: Trazodone itself causes CNS depression. Concomitant use with alcohol, benzodiazepines (e.g., alprazolam, diazepam), opioids, other sedatives, or hypnotics can significantly increase sedation, drowsiness, respiratory depression, and cognitive impairment.
* **Drugs Metabolized by CYP3A4**: Trazodone is metabolized by the CYP3A4 enzyme. Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nefazodone) can increase trazodone concentrations, leading to increased risk of side effects. Conversely, strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) can decrease trazodone levels, potentially reducing its effectiveness.
* **Warfarin**: Trazodone may rarely alter the anticoagulant effects of warfarin, requiring close monitoring of INR.
* **Digoxin/Phenytoin**: Trazodone has been reported to increase serum levels of digoxin and phenytoin in some cases.
* **Antihypertensive Drugs**: Due to its alpha-1 adrenergic blocking activity, trazodone can potentiate the hypotensive effects of antihypertensive medications, leading to an increased risk of dizziness and fainting.
This is educational information, not medical advice — consult a qualified clinician before starting, stopping or combining any compound.
Trazodone is typically taken once daily, and individual needs vary — talk to a licensed clinician. Due to its significant sedative effects, it is most commonly administered in the evening, usually before bedtime, to help mitigate daytime drowsiness and leverage its sleep-inducing properties. It can be taken with or without food. Taking it with food may help reduce the incidence of nausea and stomach upset, which are common side effects for some individuals (Source: FDA label). Consistency in timing is often recommended to maintain stable drug levels and optimize therapeutic effects.
Source for this section: Sources for When should you take Trazodone?: Jumps to this entry in the sources and references list at the end of the page.
What interacts with Trazodone?
| Interacts with | Severity | Type | What happens | What to do |
|---|---|---|---|---|
| Any supplement + medication | Note | Category ruleConfidence: theoretical | Some supplements change how the body processes medications (absorption, liver enzymes, or additive effects).Source pending | Specific pairs are checked against a licensed drug database and shown with their own severity. Always confirm with your provider or pharmacist. |
| Any vitamin + medication | Note | Category ruleConfidence: theoretical | Certain vitamins interact with specific medications (e.g., vitamin K with blood thinners).Source pending | Specific pairs are checked against a licensed source; confirm with your provider. |
| Melatonin | Note | Compound pairConfidence: theoretical | Additive sedation possible.Source pending | Start at low melatonin dose (0.3–1 mg) when combined with prescription sedatives. |
Frequently asked questions about Trazodone
Trazodone is a medication. It is also known as Desyrel. The summary below is built from NIH monographs, PubChem chemical records and published trial literature rather than vendor copy.
Trazodone is commonly discussed in the context of the goals discussed on its profile page. Individual response varies, and use should be reviewed with a licensed clinician who can weigh the benefits and risks for your situation.
For Trazodone, it is typically taken in the evening. Always follow the specific dose your clinician or the product label prescribes.
Trazodone carries potential side effects and drug interactions, documented in NIH, Mayo Clinic, and FDA label sources. Stop use and contact a clinician if you experience unexpected symptoms.
Interaction risk for Trazodone comes from the rest of the stack: other medications, prescription medicines, hormone therapy and peptides. Because Trazodone is usually taken in the evening, most avoidable conflicts come from what else lands in that same window. Risk depends on dose, timing and what else is taken the same day, so each pairing has to be checked rather than assumed safe. The free checker at https://doseroutine.com/interaction-checker covers Trazodone with no sign-up.
There is no single answer for Trazodone plus TRT. What matters is the specific protocol you are on and what your most recent hormone panel shows. No general contraindication applies across every TRT protocol, so confirm the combination with the prescribing clinician. See the free TRT interaction reference: https://doseroutine.com/trt-supplement-interactions
Pairing Trazodone with peptides has to be assessed one peptide at a time, because GLP-1 agonists, secretagogues, healing peptides and melanocortins do not share an interaction profile. Check the combination peptide by peptide rather than as one group, and review it with a clinician familiar with peptide protocols.
Published frequency for Trazodone varies by protocol and formulation, so the label or prescription is what sets it. It is typically taken in the evening. Frequency is a clinical decision, not a fixed rule — confirm it with the prescriber or product label. Comparison of apps that keep a schedule like this: https://doseroutine.com/best-dose-tracking-apps
The effect of a missed dose of Trazodone depends on the protocol and formulation you are on. Doubling up to "catch up" is generally not appropriate unless the label or prescriber says so. Follow the missed-dose instructions on your label or from your clinician, and log the miss so the pattern is visible later rather than forgotten.
For Trazodone the useful record is the dose, the time it was actually taken, and what else was taken in the same window. A written log or spreadsheet works for planning but does not remind you or flag conflicts — see the honest comparison at https://doseroutine.com/vs/spreadsheet and the wider roundup at https://doseroutine.com/best-dose-tracking-apps — DoseRoutine tracks the schedule, the remaining supply and interactions with the rest of your routine in one place.
Which studies looked at Trazodone?
Peer-reviewed research indexed in PubMed. Each entry links to the original record.
- 1.Fatal overdose with trazodone: case report and literature review(opens PubMed in a new tab)Acta Clin Belg · 2001 · PMID 11603256 · https://pubmed.ncbi.nlm.nih.gov/11603256/
- 2.Effects of Trazodone on Sleep: A Systematic Review and Meta-analysis(opens PubMed in a new tab)CNS Drugs · 2024 · PMID 39123094 · https://pubmed.ncbi.nlm.nih.gov/39123094/
Sources cited on this page
Specific documents referenced by the numbered markers above. Each number matches the marker in the text.
- PubChem CID 5533(opens in a new tab)National Center for Biotechnology Information · pubchem.ncbi.nlm.nih.gov/compound/5533
Verify at
Publisher search links for Trazodone. These are places to check the information — they are not citations, so they are not numbered.
- FDA-approved labeling (DailyMed)(publisher search, opens in a new tab)U.S. Food and Drug Administration · publisher search
- DrugBank(publisher search, opens in a new tab)DrugBank Online · publisher search
- Mayo Clinic(publisher search, opens in a new tab)Mayo Clinic · publisher search
- MedlinePlus(publisher search, opens in a new tab)U.S. National Library of Medicine · publisher search
- Cochrane Library(publisher search, opens in a new tab)Cochrane · publisher search
- PubMed literature search(publisher search, opens in a new tab)National Library of Medicine · publisher search
- Wikipedia entry(publisher search, opens in a new tab)Wikipedia · publisher search
DoseRoutine compiles summaries from publicly available scientific and regulatory references. Always verify important decisions with a licensed clinician. How we source and review this information.
What is the short answer on Trazodone?
Plain-text summary, safe to quote verbatim:
Trazodone is an antidepressant medication that belongs to the class of serotonin antagonist and reuptake inhibitors (SARIs). It is primarily approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depressive disorder. It is typically taken in the evening.
Source: DoseRoutine — https://doseroutine.com/library/trazodone
Cite this page
Using this in an article, AI answer, or research note? Please attribute:
DoseRoutine. (2026). Trazodone — Overview, Benefits & Side Effects. Retrieved from https://doseroutine.com/library/trazodone
What compounds are similar to Trazodone?
Others in the medication category or studied for the same goals.