trazodone (Desyrel)

How long the trials actually ran

We could not establish a longest trial length for trazodone. That is a gap in what we can show you — not evidence that the trials ran long.

The label asserts that efficacy was established but does not say in how many trials, for how long, or in how many people. There is nothing here to weigh.

The gap between how long the trials ran and how long people actually take these medications is the single most important thing on this page. It is not evidence that longer use is unsafe or ineffective. It is evidence that longer use was not what got tested.

How many Americans take trazodone

Survey-based federal estimates, published with a lag of about two years. They count prescriptions filled, not outcomes.

26,159,531

prescriptions in the United States (2024)

6,424,130

people filling them (2024)

Prescriptions are up 2% since 2014. Whatever you decide about trazodone, you are deciding alongside about 6,424,130 other people this year.

Source: ClinCalc DrugStats (Medical Expenditure Panel Survey (MEPS), Agency for Healthcare Research and Quality), CC BY-SA 4.0, release 2026.08.

What people report to the FDA about trazodone

15,550

reports mentioning trazodone, all time

10,381

filed as serious (a report-level flag covering every drug and outcome in the report)

Source: FDA Adverse Event Reporting System (FAERS), via openFDA, data through 2026-07-30.

Known interactions, from the label

The FDA label’s interactions section, verbatim. A pharmacist checking your actual medication list beats any published list — including this one.

FDA label for trazodone, effective August 27, 2026 — DailyMed.

Who pays for trazodone

Two claims datasets and one survey, covering different populations with different instruments — they cannot be reconciled by arithmetic, and where their sum crowds the all-payer estimate, that is a finding about the estimates rather than a percentage.

Medicare Part D

Read the under-65 group correctly before the numbers: Medicare before 65 means the disabled and dual-eligible population — among the sickest, highest-need people in the program — and reading their utilization as typical adult use would be a category error. The beneficiary total sums brand-level rows, so treat it as an upper bound on distinct people. 3,943,410 beneficiaries filled 18,417,710 claims in 2024 — 3,175,939 aged 65 and over, and 767,471 under 65.

Medicaid

At least 7,935,647 prescriptions in 2024 — a floor, because 58 of 504 national data rows are suppressed for privacy and contribute zero. Medicaid covers more children than any insurer in the country and publishes no age split — how much of this number is pediatric use is not knowable from public data.

All payers (survey estimate)

The MEPS-based estimate above puts the whole country at 26,159,531 prescriptions and 6,424,130 people in 2024. Subtracting the public programs from it would produce a number for everyone else — and we do not print that number, because subtracting a survey from claims counts manufactures precision that does not exist.

The population nobody counts

The commercially insured working-age adult — statistically, the likeliest person to be reading this page — is the one population with no public per-drug count anywhere. Private claims data exists and is sold, but nothing a patient can check is published. For children the record is thinner still: no public source counts pediatric use of trazodone specifically; the closest the public record comes is condition-level treatment rates for children, which we have traced for one condition in how childhood ADHD got counted.

Sources: Medicare Part D Prescribers — by Geography and Drug, data.cms.gov, National rows, data year 2024 (published with ~17-month lag). Medicaid State Drug Utilization Data 2024, data.medicaid.gov, national aggregate rows. Retrieved 2026-09-01.

The approval, step by step

1. Step 1

   What the approval was actually based on

   Which studies did the FDA rely on, how long did they run, and who was in them?

   The efficacy and safety of trazodone hydrochloride were established from inpatient and outpatient trials of the trazodone immediate release formulation in the treatment of major depressive disorder.

   FDA-approved labelling, 14. Clinical Studies (from a generic manufacturer's label — the brand application has no current label on file, so this text is FDA-cleared but is not the original approval document) — read the label on DailyMed

   Our reading

   That is the entire clinical studies section. Two hundred and nineteen characters, and it contains no number: not how many trials, not how many people, not how many weeks. The label states the conclusion and withholds the evidence, so there is nothing here to weigh and we do not pretend otherwise. This matters more for trazodone than for most drugs on this list, because the overwhelming majority of trazodone prescriptions today are low-dose, for sleep — a use that is not the approved indication and was never the subject of a registration trial at all.

2. Step 2

   The approval

   When was it approved, under what application, and by whose review?

   Approved

   December 24, 1981

   Application

   NDA018207

   Review

   STANDARD

   Holds it now

   Pragma Pharmaceuticals

   Label submissions since

   30

   Drug applications are bought and sold. The company that holds this one today is often not the company that ran the trials, and where we cannot state the original sponsor from a source we leave it blank rather than guess.

   Source: openFDA Drugs@FDA, original application ORIG-1

3. Step 3

   What was added after it was on the market

   Which warnings arrived only after millions of people were already taking it?

   • The antidepressant suicidality warning has an age ceiling most people never hear about

     Antidepressants carry a boxed warning about suicidal thoughts and behaviour in children, adolescents and young adults. It came from pooling 24 short-term placebo-controlled trials of nine antidepressants in more than 4,400 young patients: suicidality was reported in about 4% on drug against 2% on placebo. There were no completed suicides in those trials.

     The part that usually gets lost is the age boundary, which is in the label itself. The studies did not show an increased risk above age 24, and in patients 65 and older the risk went in the other direction — it was reduced. The warning is real and it is specific, not a blanket statement about everyone who takes one.

     Worth asking

     Given my age, which side of that line am I on, what specifically should I or the people around me watch for in the first two months, and who do I call if it happens.

     PROZAC (fluoxetine) prescribing information — Boxed Warning: Suicidal Thoughts and Behaviors — U.S. Food and Drug Administration (approved labelling)

4. Step 4

   What independent research has found since

   What has been learned by people who were not selling it?

   • Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major…

     37 years after approval

     Across 522 trials in 116,477 adults with major depression, trazodone worked better than placebo, but in head-to-head comparisons it was among the least effective of the 21 antidepressants and had among the highest dropout rates (odds ratios 1.30-2.32 for stopping treatment).

     Worth asking

     Worth asking your prescriber whether trazodone was chosen mainly for depression or for sleep, since several other antidepressants ranked higher for treating depression itself in this comparison.

     Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis — Cipriani A, et al. (2018)

   • Antidepressants for insomnia in adults

     37 years after approval

     Pooling 3 trials with 370 participants, low-dose trazodone gave a moderate short-term improvement in how people rated their sleep versus placebo (SMD -0.34; moderate-certainty evidence), but 2 trials with sleep-lab measurement found little or no difference in actual sleep efficiency.

     Worth asking

     Worth asking your prescriber how long you are expected to stay on trazodone for sleep, since the supporting trials were short-term and using it for insomnia is off-label.

     Antidepressants for insomnia in adults — Everitt H, et al. (2018)

   • Pharmacotherapies for sleep disturbances in dementia

     39 years after approval

     In people with moderate-to-severe Alzheimer's disease, a single 30-person trial found trazodone 50 mg for two weeks may add about 42 minutes of nighttime sleep and improve sleep efficiency by about 8.5 percentage points, with no serious adverse effects reported, but the evidence is low certainty.

     Worth asking

     Worth asking the prescriber how, after a couple of weeks, you will together judge whether trazodone is actually helping sleep in dementia, since the supporting evidence is one small short trial.

     Pharmacotherapies for sleep disturbances in dementia — McCleery J, Sharpley AL (2020)

   • Withdrawal from these medications can take months, and NICE says so

     41 years after approval

     NICE guideline NG215 covers safe prescribing and managed withdrawal for five groups of medication: opioids, benzodiazepines, gabapentinoids, Z-drugs and antidepressants. It is the closest thing there is to an official answer on how coming off actually goes.

     It states that withdrawal can be difficult and may take several months or more, that symptoms vary widely in type and severity, that they affect both physical and mental health, and that they can be delayed in onset and can persist. Two recommendations are worth quoting to a prescriber. Do not stop a medicine abruptly except in exceptional medical circumstances. And taper using a slow, stepwise reduction proportionate to the current dose, so the decrements get smaller as the dose gets lower — not a fixed cut each time.

     That last detail is the one most commonly missed. Gabapentinoids are the exception in the guideline and are reduced by a fixed amount at each step.

     Worth asking

     Can we write the taper down, what size are the steps near the end, and how long do I hold at each step before the next reduction.

     Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults (NG215) — National Institute for Health and Care Excellence (2022)

   • In 2019 the Royal College of Psychiatrists changed its position on withdrawal

     38 years after approval

     For years people reporting long, severe antidepressant withdrawal were told it lasted a week or two. In May 2019 the Royal College of Psychiatrists published a position statement conceding the point: while withdrawal symptoms are often mild and self-limiting, there is substantial variation, and for some patients symptoms last much longer and are more severe.

     It went further and asked for changes — that guidelines and patient information recognise the potential for severe and long-lasting withdrawal, that pharmacologically-informed tapering guidance be developed, that discontinuation be tapered at a rate the patient can tolerate over potentially several months, and that clinicians actively work to tell withdrawal apart from relapse.

     One thing it explicitly does not say, and it is worth being accurate about: the College states that from a clinical perspective antidepressant use is not associated with dependence in the addiction sense. Withdrawal and dependence are not the same claim.

     Worth asking

     If I feel bad three weeks after a dose reduction, how will we decide whether that is withdrawal or my depression returning, and what do we do differently in each case.

     Position statement on antidepressants and depression (PS04/19) — Royal College of Psychiatrists (2019)

   • Effects of Trazodone on Sleep: A Systematic Review and Meta-analysis

     43 years after approval

     In 44 randomized trials with 3,935 participants, trazodone (mean dose about 179 mg/day) improved rated sleep quality and added roughly 28 minutes of sleep-lab-measured sleep versus placebo, but did not change how long people felt they slept, and more than twice as many people stopped treatment because of side effects (RR 2.30).

     Worth asking

     Worth asking your prescriber what dose is planned and how side effects like next-day drowsiness will be monitored, since trial benefits for sleep came with clearly higher dropout from adverse effects.

     Effects of Trazodone on Sleep: A Systematic Review and Meta-analysis — Kokkali M, et al. (2024)

   • Trazodone for the treatment of insomnia: a meta-analysis of randomized placebo-controlled trials

     37 years after approval

     Across 7 placebo-controlled trials with 429 participants, trazodone reduced early-morning awakenings and improved how people rated their sleep quality (SMD -0.41), but did not significantly improve sleep efficiency or most objective sleep measures, with good short-term tolerability.

     Worth asking

     Worth asking your prescriber which specific sleep problem trazodone is meant to address, since trials showed better perceived sleep quality and fewer early awakenings rather than more efficient sleep overall.

     Trazodone for the treatment of insomnia: a meta-analysis of randomized placebo-controlled trials — Yi XY, et al. (2018)

5. Step 5

   What still is not known

   Which questions you might reasonably have has nobody answered yet?

   • If you take trazodone for sleep, you are taking an antidepressant off-label at a fraction of the antidepressant dose. There is no approval-grade evidence for that use.
   • The label names no trial count, no sample size and no duration. Ask why the sleep indication became near-universal without one.
   • It is prescribed for sleep largely because it is not a controlled substance and not habit-forming. That is a real advantage, and it is an argument about safety rather than about whether it works.