Trazodone

updated

Trazodone is an FDA-approved antidepressant (DESYREL, 1981) whose tablet label has no insomnia indication. Pooled insomnia trials show modest gains in perceived sleep quality and fewer night awakenings, little effect on sleep onset, and more adverse effects and dropouts than placebo. Two PubMed searches on 9 October 2026 found no trial of trazodone for sleep in stimulant users, athletes or people using performance-enhancing drugs.

Antidepressant (serotonin reuptake inhibitor and 5-HT2A antagonist)

  • FDA first approved trazodone as DESYREL for major depressive disorder on 24 December 1981; the tablet label has no insomnia indication.
  • A 2024 meta-analysis of 44 randomized trials (3,935 participants) found better sleep quality (SMD -0.58) and fewer night awakenings, no change in subjective total sleep time, and more dropouts due to adverse effects than placebo (RR 2.30).
  • The American Academy of Sleep Medicine guideline suggests clinicians not use trazodone for sleep onset or sleep maintenance insomnia in adults, a weak recommendation under GRADE.
  • Two PubMed searches on 9 October 2026 returned 9 and 10 records, and none studied sleep in stimulant users, athletes, or people using performance-enhancing drugs.
  • In a one-night caffeine model in 12 healthy men, 100 mg trazodone attenuated the drops in sleep efficiency and total sleep time.
  • The label carries a boxed warning for suicidal thoughts and behaviors in children and young adults and warns about serotonin syndrome, QT prolongation, orthostatic hypotension and priapism.

What is trazodone approved to do?

FDA first approved trazodone as DESYREL in 1981 for major depressive disorder in adults. The tablet label has no insomnia indication, so sleep use is off-label.

The trazodone hydrochloride tablet label is for major depressive disorder in adults and has no insomnia indication. The label version used here took effect on 9 July 2025.

FDA first approved trazodone as DESYREL under NDA 018207 on 24 December 1981; that product is now listed as discontinued. OLEPTRO extended-release tablets (NDA 022411, approved 2 February 2010) are also discontinued. RALDESY oral solution was approved under NDA 218637 on 26 November 2024, and generic tablet applications in the FDA records date from 1987. Approvals outside the United States are not covered here.

The active molecule is trazodone base (C19H22ClN5O, 371.9 g/mol, CAS 19794-93-5). US products use trazodone hydrochloride (C19H23Cl2N5O, 408.3 g/mol, CAS 25332-39-2; PubChem also lists 19666-36-5), and strengths are stated as trazodone hydrochloride.

Trazodone tablet label, version effective 9 July 2025: indication, warnings, adverse reactions

Official label

DailyMed, U.S. National Library of Medicine. Trazodone hydrochloride tablets, prescribing information, label version effective 9 July 2025. Set ID 4006d439-e2de-4590-82e9-fc9d56e3ec1b.

The label approves trazodone hydrochloride tablets for major depressive disorder in adults and has no insomnia indication. A boxed warning covers suicidal thoughts and behaviors in children and young adults. Warnings cover serotonin syndrome, QT prolongation and arrhythmia (torsade de pointes has been reported postmarketing at 100 mg or less of the immediate-release form), orthostatic hypotension and syncope (the label links postural hypotension to alpha-1 receptor antagonism), bleeding risk, priapism, and impaired judgment and motor skills. Men with an erection lasting more than 4 hours, painful or not, should stop the drug and seek emergency care. In the label's controlled trials, drowsiness occurred in 24% of inpatients on trazodone versus 6% on placebo and in 41% versus 20% of outpatients; hypotension in 7% versus 1% and 4% versus 0%; syncope in 3% versus 2% and 5% versus 1%. Peak plasma levels come about 1 hour after a fasting dose and about 2 hours with food, and CYP3A4 converts trazodone to the active metabolite mCPP.

Participants / model
Adults with major depressive disorder; label trials of 142 inpatients and 157 outpatients on trazodone versus 95 and 158 on placebo
Treatment
Oral immediate-release trazodone hydrochloride tablets
Follow-up
Label version effective 9 July 2025
Study design
Official prescribing information
Funding
not stated in the source

The tablet label states no half-life. It has no insomnia indication, so sleep use is off-label.

Read the original source
RALDESY label, version effective 1 September 2026: pharmacokinetics

Official label

DailyMed, U.S. National Library of Medicine. RALDESY (trazodone hydrochloride) 10 mg/mL oral solution, prescribing information, label version effective 1 September 2026. Set ID 34708cc1-b0b2-4fd0-b9f3-7f008b457fc9.

RALDESY, a 10 mg/mL trazodone hydrochloride oral solution, showed no clinically significant pharmacokinetic difference from immediate-release tablets under fed conditions. Peak levels occur about 1 hour after a fed dose, a high-fat meal lowered mean Cmax by 31% and raised mean AUC by 8%, and the average terminal elimination half-life under fed conditions is 18 hours. Trazodone is 89 to 95% protein bound and less than 1% of a dose is excreted unchanged.

Participants / model
Label PK participants
Treatment
RALDESY oral solution compared with immediate-release tablets
Follow-up
Label version effective 1 September 2026
Study design
Official prescribing information
Funding
not stated in the source

This is the only label in the records that states a half-life, and the 18-hour figure is for the oral solution under fed conditions.

Read the original source
Drugs@FDA: DESYREL 1981, OLEPTRO 2010, RALDESY 2024

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 018207 (DESYREL), with related trazodone applications NDA 022411 (OLEPTRO) and NDA 218637 (RALDESY). Dates read from the openFDA Drugs@FDA records.

FDA first approved trazodone as DESYREL under NDA 018207 on 24 December 1981; that product is now listed as discontinued. OLEPTRO extended-release tablets (NDA 022411, approved 2 February 2010) are also discontinued. RALDESY oral solution was approved under NDA 218637 on 26 November 2024. Generic tablet ANDAs in the records date from 1987.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1981 to 2024
Study design
FDA application records
Funding
not stated in the source

These records give approval dates and discontinuation status. Indications come from the product labels.

Read the original source
PubChem: trazodone and trazodone hydrochloride identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 5533 (trazodone) and CID 62935 (trazodone hydrochloride).

Trazodone base: CID 5533, C19H22ClN5O, 371.9 g/mol, CAS 19794-93-5. Trazodone hydrochloride, the salt in US products: CID 62935, C19H23Cl2N5O, 408.3 g/mol, CAS 25332-39-2 (PubChem also lists 19666-36-5). US tablet and oral-solution strengths are stated as trazodone hydrochloride.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

What did the insomnia trials find?

Pooled trials found modest gains in perceived sleep quality and fewer night awakenings, with little effect on sleep efficiency or sleep latency. The 2024 analysis also found more adverse effects and more dropouts due to adverse effects than on placebo.

A Cochrane review of antidepressants for insomnia included 23 randomized trials (2,806 participants). Three trazodone trials (370 participants) pooled to a moderate improvement in subjective sleep outcomes over placebo (SMD -0.34, 95% CI -0.66 to -0.02). Two trazodone trials using polysomnography found little or no difference in sleep efficiency (MD 1.38 percentage points, 95% CI -2.87 to 5.63; 169 participants; low-quality evidence). Low-quality evidence from two trials showed more adverse effects than placebo, including morning grogginess, dry mouth, and thirst. The review found no evidence on long-term antidepressant use for insomnia.

A meta-analysis of 7 placebo-controlled trials in patients with insomnia (429 patients) found no significant improvement in sleep efficiency (SMD 0.09, 95% CI -0.19 to 0.38). Perceived sleep quality was better than on placebo (SMD -0.41, 95% CI -0.82 to -0.00) and night awakenings were fewer (SMD -0.51, 95% CI -0.97 to -0.05), with no significant differences in sleep latency, total sleep time, or wake after sleep onset. Discontinuations for adverse events or for any cause did not differ.

A 2024 meta-analysis of 44 randomized trials (3,935 participants with sleep disturbances across diagnoses) compared trazodone with placebo for at least 5 days. It found no change in subjective total sleep time (WMD 0.73 minutes, 95% CI -24.62 to 26.07). Trazodone improved sleep quality (SMD -0.58, 95% CI -0.87 to -0.28), reduced night awakenings (SMD -0.57, 95% CI -0.85 to -0.30) and wake after sleep onset (WMD -13.47 minutes, 95% CI -23.09 to -3.86), and lengthened polysomnographic total sleep time (WMD 27.98 minutes, 95% CI 4.02 to 51.95). The authors describe only minor effects on sleep latency, sleep efficiency, and daytime impairment. Adverse effects overall (RR 1.18, 95% CI 1.03 to 1.33) and dropouts due to adverse effects (RR 2.30, 95% CI 1.45 to 3.64) were more frequent than on placebo.

Cochrane review: 23 trials, three trazodone trials in 370 participants

Systematic review and meta-analysis

Everitt H et al. Cochrane Database Syst Rev. 2018;5(5):CD010753. PMID 29761479.

The review included 23 randomized trials (2,806 participants). Three trazodone trials (370 participants) pooled to a moderate improvement in subjective sleep outcomes over placebo (SMD -0.34, 95% CI -0.66 to -0.02). Two trazodone trials using polysomnography found little or no difference in sleep efficiency (MD 1.38 percentage points, 95% CI -2.87 to 5.63; 169 participants; low-quality evidence). Low-quality evidence from two trials showed more adverse effects than placebo, including morning grogginess, dry mouth, and thirst. The review found no evidence on long-term antidepressant use for insomnia.

Participants / model
Adults with a primary diagnosis of insomnia, including people with comorbidities
Treatment
Oral trazodone versus placebo
Follow-up
not stated in the source
Study design
Cochrane systematic review and meta-analysis of 23 randomized trials
Funding
not stated in the source

The trazodone results come from three small trials. The review describes antidepressant use for insomnia as widespread.

Read the original source
Trazodone meta-analysis: 7 trials, 429 patients, no gain in sleep efficiency

Systematic review and meta-analysis

Yi XY et al. Sleep Med. 2018;45:25-32. PMID 29680424.

Across 7 placebo-controlled trials (429 patients), trazodone did not significantly improve sleep efficiency (SMD 0.09, 95% CI -0.19 to 0.38). Perceived sleep quality was better than on placebo (SMD -0.41, 95% CI -0.82 to -0.00) and night awakenings were fewer (SMD -0.51, 95% CI -0.97 to -0.05), with no significant differences in sleep latency, total sleep time, or wake after sleep onset. Discontinuations for adverse events or for any cause did not differ.

Participants / model
Patients with insomnia in randomized placebo-controlled trials
Treatment
Oral trazodone versus placebo
Follow-up
not stated in the source
Study design
Systematic review and meta-analysis of 7 randomized placebo-controlled trials
Funding
not stated in the source

This analysis found no difference in discontinuations, unlike the 2024 meta-analysis of 44 trials.

Read the original source
2024 meta-analysis: 44 trials, 3,935 participants, adverse-effect dropouts RR 2.30

Systematic review and meta-analysis

Kokkali M et al. CNS Drugs. 2024;38(10):753-769. PMID 39123094.

Across 44 randomized trials (3,935 participants), trazodone compared with placebo for at least 5 days did not change subjective total sleep time (WMD 0.73 minutes, 95% CI -24.62 to 26.07). It improved sleep quality (SMD -0.58, 95% CI -0.87 to -0.28), reduced night awakenings (SMD -0.57, 95% CI -0.85 to -0.30) and wake after sleep onset (WMD -13.47 minutes, 95% CI -23.09 to -3.86), and lengthened polysomnographic total sleep time (WMD 27.98 minutes, 95% CI 4.02 to 51.95). The authors describe only minor effects on sleep latency, sleep efficiency, and daytime impairment. Adverse effects overall (RR 1.18, 95% CI 1.03 to 1.33) and dropouts due to adverse effects (RR 2.30, 95% CI 1.45 to 3.64) were more frequent than on placebo.

Participants / model
Participants with sleep disturbances across diagnoses in randomized trials
Treatment
Oral trazodone versus placebo for at least 5 days
Follow-up
At least 5 days of treatment per trial
Study design
Systematic review and meta-analysis of 44 randomized trials
Funding
not stated in the source

The population spans several diagnoses, not only primary insomnia.

Read the original source

What does the sleep medicine guideline say about trazodone?

The American Academy of Sleep Medicine suggests that clinicians not use trazodone for sleep onset or sleep maintenance insomnia in adults. It is a weak recommendation under GRADE.

The guideline, based on a systematic review of randomized trials in adults with chronic insomnia, suggests that clinicians not use trazodone for sleep onset or sleep maintenance insomnia, compared with no treatment.

It is a weak recommendation under GRADE. The guideline says this reflects lower certainty and should not be read as showing the drug is ineffective.

AASM guideline: suggests against trazodone for insomnia (weak recommendation)

Systematic review and meta-analysis

Sateia MJ et al. J Clin Sleep Med. 2017;13(2):307-349. PMID 27998379.

The guideline suggests that clinicians not use trazodone for sleep onset or sleep maintenance insomnia in adults, compared with no treatment. It is a weak recommendation under GRADE, which the guideline says reflects lower certainty and should not be read as showing the drug is ineffective.

Participants / model
Adults with chronic insomnia
Treatment
Oral trazodone
Follow-up
not stated in the source
Study design
Clinical practice guideline (GRADE) based on a systematic review of randomized trials
Funding
not stated in the source

A guideline recommendation, not a trial. The guideline states a weak recommendation reflects lower certainty.

Read the original source

Does trazodone help sleep in stimulant users or after hard training?

No trial found tests it. Two PubMed searches on 9 October 2026, one on stimulants and one on athletes, training and performance-enhancing drugs, returned 9 and 10 records, and none studied sleep in those groups.

Sellers market trazodone for sleep onset and sleep maintenance in stimulant users and in people whose nervous system runs hot from hard training or performance-enhancing drugs. The first search, for trazodone with cocaine, methamphetamine or amphetamine and sleep or insomnia, returned 9 records. None tested trazodone for sleep in people using those drugs. They covered reviews, priapism case reports, a suspected clonidine, trazodone and dextroamphetamine interaction in a 12-year-old, a false-positive amphetamine test report, and early pharmacology papers.

The second search, for trazodone with athletes, sport, anabolic steroids, performance-enhancing drugs, resistance training, exercise or overtraining, returned 10 records. None studied sleep in athletes, people in hard training, or users of anabolic steroids or other performance-enhancing drugs. They included a 1990 case of trazodone-related exercise-induced ventricular tachycardia in a 79-year-old woman.

The nearest record is a one-night caffeine model. In a double-blind randomized crossover study in 12 healthy men, 150 mg of caffeine at bedtime delayed sleep onset and reduced total sleep time and sleep efficiency. Adding 100 mg trazodone attenuated the drops in sleep efficiency and total sleep time, increased stage 3 sleep, and reduced awakenings. It did not test amphetamines, cocaine, repeated stimulant use, or training-related sleep loss.

PubMed search, 9 October 2026: 9 records, none on sleep in stimulant users

PubMed search record

PubMed search run on 9 October 2026: trazodone AND (cocaine OR methamphetamine OR amphetamine OR amphetamines) AND (sleep OR insomnia). 9 records returned.

The search returned 9 records. None tested trazodone for sleep in people using cocaine, methamphetamine, or amphetamine. They covered reviews of substance-use care and of depression in older adults, priapism case reports, a suspected clonidine, trazodone, and dextroamphetamine interaction in a 12-year-old, a false-positive amphetamine test report, and early pharmacology papers. The stimulant-user use has no trial behind it in these records.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
PubMed search, 9 October 2026: 10 records, none on sleep in athletes or users of performance-enhancing drugs

PubMed search record

PubMed search run on 9 October 2026: trazodone[tiab] AND (athlete OR athletes OR sport OR sports OR anabolic OR performance-enhancing OR resistance training OR exercise OR overtraining)[tiab]. 10 records returned.

The search returned 10 records. None studied sleep in athletes, people in hard training, or users of anabolic steroids or other performance-enhancing drugs. They covered reviews of insomnia, dementia, addiction, and fibromyalgia, a 1990 case of trazodone-related exercise-induced ventricular tachycardia in a 79-year-old woman, a horse hair drug-testing method, and a serotonin syndrome case report.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
Caffeine model: 12 healthy men, one night, trazodone 100 mg

Randomized controlled trial

Paterson LM et al. J Psychopharmacol. 2009;23(5):487-94. PMID 19351801.

In 12 healthy men, 150 mg of caffeine at bedtime delayed sleep onset and reduced total sleep time and sleep efficiency. Adding 100 mg trazodone attenuated the drops in sleep efficiency and total sleep time, increased stage 3 sleep, and reduced awakenings.

Participants / model
12 healthy men
Treatment
Single bedtime oral dose of trazodone 100 mg with caffeine 150 mg
Follow-up
One night
Study design
Double-blind randomized crossover study with home polysomnography and sleep EEG
Funding
not stated in the source

This one-night caffeine model is the closest record to the stimulant claim. It did not test amphetamines, cocaine, repeated stimulant use, or training-related sleep loss.

Read the original source

What happened in trials in other substance-use settings?

Results were mixed. After alcohol detoxification, sleep quality improved during treatment but not after stopping, and drinking outcomes were worse. In methadone-maintained adults, trazodone did not improve sleep.

In 173 adults after alcohol detoxification who reported sleep disturbance (88 trazodone, 85 placebo), trazodone 50 to 150 mg at bedtime for 12 weeks improved Pittsburgh Sleep Quality Index scores during treatment (mean change -3.02, 95% CI -3.38 to -2.67), but sleep quality matched placebo after it was stopped. The trazodone group had less improvement in the proportion of days abstinent during treatment (mean change -0.12, 95% CI -0.15 to -0.09) and more drinks per drinking day after stopping (mean change 4.6, 95% CI 2.1 to 7.1).

In 137 methadone-maintained adults with sleep complaints, trazodone did not improve subjective or polysomnographic sleep. Without correction for multiple comparisons, 1 of 21 sleep measures differed, the 6-month effect on the Pittsburgh Sleep Quality Index was not significant (p = .10), and illicit drug use did not change.

Neither trial enrolled stimulant users, so neither addresses the stimulant claim.

After alcohol detoxification: 173 adults, 12 weeks, more drinking after stopping

Randomized controlled trial

Friedmann PD et al. Alcohol Clin Exp Res. 2008;32(9):1652-60. PMID 18616688.

Trazodone improved Pittsburgh Sleep Quality Index scores during treatment (mean change -3.02, 95% CI -3.38 to -2.67), but sleep quality matched placebo after it was stopped. The trazodone group had less improvement in the proportion of days abstinent during treatment (mean change -0.12, 95% CI -0.15 to -0.09) and more drinks per drinking day after stopping (mean change 4.6, 95% CI 2.1 to 7.1).

Participants / model
173 adults after alcohol detoxification who reported sleep disturbance (88 trazodone, 85 placebo)
Treatment
Oral trazodone 50 to 150 mg at bedtime, or placebo
Follow-up
12 weeks of treatment, outcomes over 6 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

This trial reported drinking outcomes, and the trazodone group did worse on them. It did not enroll stimulant users.

Read the original source
Methadone maintenance: 137 adults, no sleep improvement

Randomized controlled trial

Stein MD et al. Drug Alcohol Depend. 2012;120(1-3):65-73. PMID 21798674.

Trazodone did not improve subjective or polysomnographic sleep: without correction for multiple comparisons, 1 of 21 sleep measures differed, the 6-month effect on the Pittsburgh Sleep Quality Index was not significant (p = .10), and illicit drug use did not change.

Participants / model
137 adults on methadone maintenance with a PSQI score of 6 or higher
Treatment
Oral trazodone versus placebo
Follow-up
6-month outcome
Study design
Randomized placebo-controlled trial with two-night home polysomnography
Funding
not stated in the source

The population was adults on methadone maintenance, not stimulant users.

Read the original source

How does trazodone work, and what does the body do with it?

The label pharmacology section describes serotonin reuptake inhibition plus 5-HT2A antagonism. The 18-hour half-life comes from the oral-solution label in the fed state, and the tablet label states none.

The label pharmacology section describes serotonin reuptake inhibition plus 5-HT2A antagonism. The label links postural hypotension to alpha-1 receptor antagonism, and CYP3A4 converts trazodone to the active metabolite mCPP.

For the tablet, peak plasma levels come about 1 hour after a fasting dose and about 2 hours with food. For the RALDESY oral solution, which showed no clinically significant pharmacokinetic difference from immediate-release tablets under fed conditions, peak levels occur about 1 hour after a fed dose. A high-fat meal lowered mean Cmax by 31% and raised mean AUC by 8%, and the average terminal elimination half-life under fed conditions is 18 hours.

Trazodone is 89 to 95% protein bound and less than 1% of a dose is excreted unchanged. The tablet label states no half-life.

Trazodone tablet label, version effective 9 July 2025: indication, warnings, adverse reactions

Official label

DailyMed, U.S. National Library of Medicine. Trazodone hydrochloride tablets, prescribing information, label version effective 9 July 2025. Set ID 4006d439-e2de-4590-82e9-fc9d56e3ec1b.

The label approves trazodone hydrochloride tablets for major depressive disorder in adults and has no insomnia indication. A boxed warning covers suicidal thoughts and behaviors in children and young adults. Warnings cover serotonin syndrome, QT prolongation and arrhythmia (torsade de pointes has been reported postmarketing at 100 mg or less of the immediate-release form), orthostatic hypotension and syncope (the label links postural hypotension to alpha-1 receptor antagonism), bleeding risk, priapism, and impaired judgment and motor skills. Men with an erection lasting more than 4 hours, painful or not, should stop the drug and seek emergency care. In the label's controlled trials, drowsiness occurred in 24% of inpatients on trazodone versus 6% on placebo and in 41% versus 20% of outpatients; hypotension in 7% versus 1% and 4% versus 0%; syncope in 3% versus 2% and 5% versus 1%. Peak plasma levels come about 1 hour after a fasting dose and about 2 hours with food, and CYP3A4 converts trazodone to the active metabolite mCPP.

Participants / model
Adults with major depressive disorder; label trials of 142 inpatients and 157 outpatients on trazodone versus 95 and 158 on placebo
Treatment
Oral immediate-release trazodone hydrochloride tablets
Follow-up
Label version effective 9 July 2025
Study design
Official prescribing information
Funding
not stated in the source

The tablet label states no half-life. It has no insomnia indication, so sleep use is off-label.

Read the original source
RALDESY label, version effective 1 September 2026: pharmacokinetics

Official label

DailyMed, U.S. National Library of Medicine. RALDESY (trazodone hydrochloride) 10 mg/mL oral solution, prescribing information, label version effective 1 September 2026. Set ID 34708cc1-b0b2-4fd0-b9f3-7f008b457fc9.

RALDESY, a 10 mg/mL trazodone hydrochloride oral solution, showed no clinically significant pharmacokinetic difference from immediate-release tablets under fed conditions. Peak levels occur about 1 hour after a fed dose, a high-fat meal lowered mean Cmax by 31% and raised mean AUC by 8%, and the average terminal elimination half-life under fed conditions is 18 hours. Trazodone is 89 to 95% protein bound and less than 1% of a dose is excreted unchanged.

Participants / model
Label PK participants
Treatment
RALDESY oral solution compared with immediate-release tablets
Follow-up
Label version effective 1 September 2026
Study design
Official prescribing information
Funding
not stated in the source

This is the only label in the records that states a half-life, and the 18-hour figure is for the oral solution under fed conditions.

Read the original source

What risks do the label and reports show?

The label carries a boxed warning for suicidal thoughts and behaviors in children and young adults. Its warnings cover serotonin syndrome, QT prolongation, orthostatic hypotension, bleeding, priapism, and impaired judgment and motor skills.

A boxed warning covers suicidal thoughts and behaviors in children and young adults. Warnings cover serotonin syndrome, QT prolongation and arrhythmia, orthostatic hypotension and syncope, bleeding risk, priapism, and impaired judgment and motor skills. Torsade de pointes has been reported postmarketing at 100 mg or less of the immediate-release form, so the QT warning is not limited to higher doses. The label links postural hypotension to alpha-1 receptor antagonism.

In the label's controlled trials, drowsiness occurred in 24% of inpatients on trazodone versus 6% on placebo and in 41% versus 20% of outpatients. Hypotension occurred in 7% versus 1% and 4% versus 0%, and syncope in 3% versus 2% and 5% versus 1%. The trials enrolled 142 inpatients and 157 outpatients on trazodone versus 95 and 158 on placebo.

Men with an erection lasting more than 4 hours, painful or not, should stop the drug and seek emergency care, according to the label. In FDA Adverse Event Reporting System data for 2015 to 2020, 1,233 priapism reports were identified. Among drugs with at least 30 reports, trazodone, olanzapine, and tadalafil showed disproportionate reporting, with proportional reporting ratios of 9.04 (95% CI 7.73 to 10.58), 1.55, and 1.42. Spontaneous reports show a signal, not an incidence rate, so how often priapism occurs on trazodone is not established here.

Trazodone tablet label, version effective 9 July 2025: indication, warnings, adverse reactions

Official label

DailyMed, U.S. National Library of Medicine. Trazodone hydrochloride tablets, prescribing information, label version effective 9 July 2025. Set ID 4006d439-e2de-4590-82e9-fc9d56e3ec1b.

The label approves trazodone hydrochloride tablets for major depressive disorder in adults and has no insomnia indication. A boxed warning covers suicidal thoughts and behaviors in children and young adults. Warnings cover serotonin syndrome, QT prolongation and arrhythmia (torsade de pointes has been reported postmarketing at 100 mg or less of the immediate-release form), orthostatic hypotension and syncope (the label links postural hypotension to alpha-1 receptor antagonism), bleeding risk, priapism, and impaired judgment and motor skills. Men with an erection lasting more than 4 hours, painful or not, should stop the drug and seek emergency care. In the label's controlled trials, drowsiness occurred in 24% of inpatients on trazodone versus 6% on placebo and in 41% versus 20% of outpatients; hypotension in 7% versus 1% and 4% versus 0%; syncope in 3% versus 2% and 5% versus 1%. Peak plasma levels come about 1 hour after a fasting dose and about 2 hours with food, and CYP3A4 converts trazodone to the active metabolite mCPP.

Participants / model
Adults with major depressive disorder; label trials of 142 inpatients and 157 outpatients on trazodone versus 95 and 158 on placebo
Treatment
Oral immediate-release trazodone hydrochloride tablets
Follow-up
Label version effective 9 July 2025
Study design
Official prescribing information
Funding
not stated in the source

The tablet label states no half-life. It has no insomnia indication, so sleep use is off-label.

Read the original source
FAERS priapism: 1,233 reports, trazodone PRR 9.04

Human study

Schifano N et al. Int J Impot Res. 2024;36(1):50-54. PMID 35597798.

1,233 priapism reports were identified. Among drugs with at least 30 reports, trazodone, olanzapine, and tadalafil showed disproportionate reporting, with proportional reporting ratios of 9.04 (95% CI 7.73 to 10.58), 1.55, and 1.42. Spontaneous reports show a signal, not an incidence rate.

Participants / model
Spontaneous adverse-event reports in the US FDA database
Treatment
Not formulation-specific
Follow-up
Reports from 2015 to 2020
Study design
Pharmacovigilance disproportionality analysis
Funding
not stated in the source

A reporting signal, not an incidence rate. Priapism incidence for trazodone is not established by this source.

Read the original source
2024 meta-analysis: 44 trials, 3,935 participants, adverse-effect dropouts RR 2.30

Systematic review and meta-analysis

Kokkali M et al. CNS Drugs. 2024;38(10):753-769. PMID 39123094.

Across 44 randomized trials (3,935 participants), trazodone compared with placebo for at least 5 days did not change subjective total sleep time (WMD 0.73 minutes, 95% CI -24.62 to 26.07). It improved sleep quality (SMD -0.58, 95% CI -0.87 to -0.28), reduced night awakenings (SMD -0.57, 95% CI -0.85 to -0.30) and wake after sleep onset (WMD -13.47 minutes, 95% CI -23.09 to -3.86), and lengthened polysomnographic total sleep time (WMD 27.98 minutes, 95% CI 4.02 to 51.95). The authors describe only minor effects on sleep latency, sleep efficiency, and daytime impairment. Adverse effects overall (RR 1.18, 95% CI 1.03 to 1.33) and dropouts due to adverse effects (RR 2.30, 95% CI 1.45 to 3.64) were more frequent than on placebo.

Participants / model
Participants with sleep disturbances across diagnoses in randomized trials
Treatment
Oral trazodone versus placebo for at least 5 days
Follow-up
At least 5 days of treatment per trial
Study design
Systematic review and meta-analysis of 44 randomized trials
Funding
not stated in the source

The population spans several diagnoses, not only primary insomnia.

Read the original source

How did low-dose trazodone compare with benzodiazepines for fall injuries?

In nursing-home residents aged 66 and older, 90-day fall-injury incidence was 5.7% after low-dose trazodone and 6.0% after a benzodiazepine, so trazodone was no safer for falls.

A population-based matched cohort in Ontario, Canada compared 7,791 matched pairs of nursing-home residents aged 66 and older who newly started low-dose oral trazodone or a benzodiazepine. The 90-day cumulative incidence of a fall-related injury leading to an emergency department visit or hospital admission was 5.7% with trazodone and 6.0% with a benzodiazepine (hazard ratio 0.94, 95% CI 0.83 to 1.08).

The authors concluded low-dose trazodone was no safer than benzodiazepines for fall injuries. The data are observational and come from older nursing-home residents.

Nursing-home cohort: 7,791 matched pairs, fall injury 5.7% versus 6.0%

Human study

Bronskill SE et al. J Am Geriatr Soc. 2018;66(10):1963-1971. PMID 30247773.

The 90-day cumulative incidence of a fall-related injury leading to an emergency department visit or hospital admission was 5.7% after starting low-dose trazodone and 6.0% after starting a benzodiazepine (hazard ratio 0.94, 95% CI 0.83 to 1.08). Low-dose trazodone was no safer than benzodiazepines for fall injuries.

Participants / model
Nursing-home residents aged 66 and older in Ontario, Canada (7,791 matched pairs)
Treatment
Newly dispensed low-dose oral trazodone versus benzodiazepines
Follow-up
90-day follow-up
Study design
Population-based matched cohort study
Funding
not stated in the source

Observational data in older nursing-home residents. It does not describe younger adults.

Read the original source

Why does trazodone sit in A tier?

FDA approval for major depressive disorder since 1981 and widespread off-label use for sleep support the A grade. The sleep trials are modest, and no trial tests the supplier's stimulant or training claim.

The A fits an approved medicine used well beyond its narrow label. The Cochrane review describes antidepressant use for insomnia as widespread. Pooled trials show modest gains in perceived sleep quality and sleep continuity, little effect on sleep onset, and more adverse effects and dropouts than placebo, and the American Academy of Sleep Medicine guideline suggests against trazodone for insomnia.

The supplier's claim gets its own verdict: no trial tests trazodone in stimulant users, athletes, or people using performance-enhancing drugs. The nearest evidence is a one-night caffeine model in 12 healthy men, and trials in other substance-use settings were mixed, with one finding more drinking after trazodone was stopped.

Trazodone tablet label, version effective 9 July 2025: indication, warnings, adverse reactions

Official label

DailyMed, U.S. National Library of Medicine. Trazodone hydrochloride tablets, prescribing information, label version effective 9 July 2025. Set ID 4006d439-e2de-4590-82e9-fc9d56e3ec1b.

The label approves trazodone hydrochloride tablets for major depressive disorder in adults and has no insomnia indication. A boxed warning covers suicidal thoughts and behaviors in children and young adults. Warnings cover serotonin syndrome, QT prolongation and arrhythmia (torsade de pointes has been reported postmarketing at 100 mg or less of the immediate-release form), orthostatic hypotension and syncope (the label links postural hypotension to alpha-1 receptor antagonism), bleeding risk, priapism, and impaired judgment and motor skills. Men with an erection lasting more than 4 hours, painful or not, should stop the drug and seek emergency care. In the label's controlled trials, drowsiness occurred in 24% of inpatients on trazodone versus 6% on placebo and in 41% versus 20% of outpatients; hypotension in 7% versus 1% and 4% versus 0%; syncope in 3% versus 2% and 5% versus 1%. Peak plasma levels come about 1 hour after a fasting dose and about 2 hours with food, and CYP3A4 converts trazodone to the active metabolite mCPP.

Participants / model
Adults with major depressive disorder; label trials of 142 inpatients and 157 outpatients on trazodone versus 95 and 158 on placebo
Treatment
Oral immediate-release trazodone hydrochloride tablets
Follow-up
Label version effective 9 July 2025
Study design
Official prescribing information
Funding
not stated in the source

The tablet label states no half-life. It has no insomnia indication, so sleep use is off-label.

Read the original source
Drugs@FDA: DESYREL 1981, OLEPTRO 2010, RALDESY 2024

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 018207 (DESYREL), with related trazodone applications NDA 022411 (OLEPTRO) and NDA 218637 (RALDESY). Dates read from the openFDA Drugs@FDA records.

FDA first approved trazodone as DESYREL under NDA 018207 on 24 December 1981; that product is now listed as discontinued. OLEPTRO extended-release tablets (NDA 022411, approved 2 February 2010) are also discontinued. RALDESY oral solution was approved under NDA 218637 on 26 November 2024. Generic tablet ANDAs in the records date from 1987.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1981 to 2024
Study design
FDA application records
Funding
not stated in the source

These records give approval dates and discontinuation status. Indications come from the product labels.

Read the original source
Cochrane review: 23 trials, three trazodone trials in 370 participants

Systematic review and meta-analysis

Everitt H et al. Cochrane Database Syst Rev. 2018;5(5):CD010753. PMID 29761479.

The review included 23 randomized trials (2,806 participants). Three trazodone trials (370 participants) pooled to a moderate improvement in subjective sleep outcomes over placebo (SMD -0.34, 95% CI -0.66 to -0.02). Two trazodone trials using polysomnography found little or no difference in sleep efficiency (MD 1.38 percentage points, 95% CI -2.87 to 5.63; 169 participants; low-quality evidence). Low-quality evidence from two trials showed more adverse effects than placebo, including morning grogginess, dry mouth, and thirst. The review found no evidence on long-term antidepressant use for insomnia.

Participants / model
Adults with a primary diagnosis of insomnia, including people with comorbidities
Treatment
Oral trazodone versus placebo
Follow-up
not stated in the source
Study design
Cochrane systematic review and meta-analysis of 23 randomized trials
Funding
not stated in the source

The trazodone results come from three small trials. The review describes antidepressant use for insomnia as widespread.

Read the original source
2024 meta-analysis: 44 trials, 3,935 participants, adverse-effect dropouts RR 2.30

Systematic review and meta-analysis

Kokkali M et al. CNS Drugs. 2024;38(10):753-769. PMID 39123094.

Across 44 randomized trials (3,935 participants), trazodone compared with placebo for at least 5 days did not change subjective total sleep time (WMD 0.73 minutes, 95% CI -24.62 to 26.07). It improved sleep quality (SMD -0.58, 95% CI -0.87 to -0.28), reduced night awakenings (SMD -0.57, 95% CI -0.85 to -0.30) and wake after sleep onset (WMD -13.47 minutes, 95% CI -23.09 to -3.86), and lengthened polysomnographic total sleep time (WMD 27.98 minutes, 95% CI 4.02 to 51.95). The authors describe only minor effects on sleep latency, sleep efficiency, and daytime impairment. Adverse effects overall (RR 1.18, 95% CI 1.03 to 1.33) and dropouts due to adverse effects (RR 2.30, 95% CI 1.45 to 3.64) were more frequent than on placebo.

Participants / model
Participants with sleep disturbances across diagnoses in randomized trials
Treatment
Oral trazodone versus placebo for at least 5 days
Follow-up
At least 5 days of treatment per trial
Study design
Systematic review and meta-analysis of 44 randomized trials
Funding
not stated in the source

The population spans several diagnoses, not only primary insomnia.

Read the original source
AASM guideline: suggests against trazodone for insomnia (weak recommendation)

Systematic review and meta-analysis

Sateia MJ et al. J Clin Sleep Med. 2017;13(2):307-349. PMID 27998379.

The guideline suggests that clinicians not use trazodone for sleep onset or sleep maintenance insomnia in adults, compared with no treatment. It is a weak recommendation under GRADE, which the guideline says reflects lower certainty and should not be read as showing the drug is ineffective.

Participants / model
Adults with chronic insomnia
Treatment
Oral trazodone
Follow-up
not stated in the source
Study design
Clinical practice guideline (GRADE) based on a systematic review of randomized trials
Funding
not stated in the source

A guideline recommendation, not a trial. The guideline states a weak recommendation reflects lower certainty.

Read the original source
PubMed search, 9 October 2026: 9 records, none on sleep in stimulant users

PubMed search record

PubMed search run on 9 October 2026: trazodone AND (cocaine OR methamphetamine OR amphetamine OR amphetamines) AND (sleep OR insomnia). 9 records returned.

The search returned 9 records. None tested trazodone for sleep in people using cocaine, methamphetamine, or amphetamine. They covered reviews of substance-use care and of depression in older adults, priapism case reports, a suspected clonidine, trazodone, and dextroamphetamine interaction in a 12-year-old, a false-positive amphetamine test report, and early pharmacology papers. The stimulant-user use has no trial behind it in these records.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
PubMed search, 9 October 2026: 10 records, none on sleep in athletes or users of performance-enhancing drugs

PubMed search record

PubMed search run on 9 October 2026: trazodone[tiab] AND (athlete OR athletes OR sport OR sports OR anabolic OR performance-enhancing OR resistance training OR exercise OR overtraining)[tiab]. 10 records returned.

The search returned 10 records. None studied sleep in athletes, people in hard training, or users of anabolic steroids or other performance-enhancing drugs. They covered reviews of insomnia, dementia, addiction, and fibromyalgia, a 1990 case of trazodone-related exercise-induced ventricular tachycardia in a 79-year-old woman, a horse hair drug-testing method, and a serotonin syndrome case report.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source

Studies and sources

Trazodone tablet label, version effective 9 July 2025: indication, warnings, adverse reactions

Official label

DailyMed, U.S. National Library of Medicine. Trazodone hydrochloride tablets, prescribing information, label version effective 9 July 2025. Set ID 4006d439-e2de-4590-82e9-fc9d56e3ec1b.

The label approves trazodone hydrochloride tablets for major depressive disorder in adults and has no insomnia indication. A boxed warning covers suicidal thoughts and behaviors in children and young adults. Warnings cover serotonin syndrome, QT prolongation and arrhythmia (torsade de pointes has been reported postmarketing at 100 mg or less of the immediate-release form), orthostatic hypotension and syncope (the label links postural hypotension to alpha-1 receptor antagonism), bleeding risk, priapism, and impaired judgment and motor skills. Men with an erection lasting more than 4 hours, painful or not, should stop the drug and seek emergency care. In the label's controlled trials, drowsiness occurred in 24% of inpatients on trazodone versus 6% on placebo and in 41% versus 20% of outpatients; hypotension in 7% versus 1% and 4% versus 0%; syncope in 3% versus 2% and 5% versus 1%. Peak plasma levels come about 1 hour after a fasting dose and about 2 hours with food, and CYP3A4 converts trazodone to the active metabolite mCPP.

Participants / model
Adults with major depressive disorder; label trials of 142 inpatients and 157 outpatients on trazodone versus 95 and 158 on placebo
Treatment
Oral immediate-release trazodone hydrochloride tablets
Follow-up
Label version effective 9 July 2025
Study design
Official prescribing information
Funding
not stated in the source

The tablet label states no half-life. It has no insomnia indication, so sleep use is off-label.

Read the original source
RALDESY label, version effective 1 September 2026: pharmacokinetics

Official label

DailyMed, U.S. National Library of Medicine. RALDESY (trazodone hydrochloride) 10 mg/mL oral solution, prescribing information, label version effective 1 September 2026. Set ID 34708cc1-b0b2-4fd0-b9f3-7f008b457fc9.

RALDESY, a 10 mg/mL trazodone hydrochloride oral solution, showed no clinically significant pharmacokinetic difference from immediate-release tablets under fed conditions. Peak levels occur about 1 hour after a fed dose, a high-fat meal lowered mean Cmax by 31% and raised mean AUC by 8%, and the average terminal elimination half-life under fed conditions is 18 hours. Trazodone is 89 to 95% protein bound and less than 1% of a dose is excreted unchanged.

Participants / model
Label PK participants
Treatment
RALDESY oral solution compared with immediate-release tablets
Follow-up
Label version effective 1 September 2026
Study design
Official prescribing information
Funding
not stated in the source

This is the only label in the records that states a half-life, and the 18-hour figure is for the oral solution under fed conditions.

Read the original source
Drugs@FDA: DESYREL 1981, OLEPTRO 2010, RALDESY 2024

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 018207 (DESYREL), with related trazodone applications NDA 022411 (OLEPTRO) and NDA 218637 (RALDESY). Dates read from the openFDA Drugs@FDA records.

FDA first approved trazodone as DESYREL under NDA 018207 on 24 December 1981; that product is now listed as discontinued. OLEPTRO extended-release tablets (NDA 022411, approved 2 February 2010) are also discontinued. RALDESY oral solution was approved under NDA 218637 on 26 November 2024. Generic tablet ANDAs in the records date from 1987.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1981 to 2024
Study design
FDA application records
Funding
not stated in the source

These records give approval dates and discontinuation status. Indications come from the product labels.

Read the original source
Cochrane review: 23 trials, three trazodone trials in 370 participants

Systematic review and meta-analysis

Everitt H et al. Cochrane Database Syst Rev. 2018;5(5):CD010753. PMID 29761479.

The review included 23 randomized trials (2,806 participants). Three trazodone trials (370 participants) pooled to a moderate improvement in subjective sleep outcomes over placebo (SMD -0.34, 95% CI -0.66 to -0.02). Two trazodone trials using polysomnography found little or no difference in sleep efficiency (MD 1.38 percentage points, 95% CI -2.87 to 5.63; 169 participants; low-quality evidence). Low-quality evidence from two trials showed more adverse effects than placebo, including morning grogginess, dry mouth, and thirst. The review found no evidence on long-term antidepressant use for insomnia.

Participants / model
Adults with a primary diagnosis of insomnia, including people with comorbidities
Treatment
Oral trazodone versus placebo
Follow-up
not stated in the source
Study design
Cochrane systematic review and meta-analysis of 23 randomized trials
Funding
not stated in the source

The trazodone results come from three small trials. The review describes antidepressant use for insomnia as widespread.

Read the original source
Trazodone meta-analysis: 7 trials, 429 patients, no gain in sleep efficiency

Systematic review and meta-analysis

Yi XY et al. Sleep Med. 2018;45:25-32. PMID 29680424.

Across 7 placebo-controlled trials (429 patients), trazodone did not significantly improve sleep efficiency (SMD 0.09, 95% CI -0.19 to 0.38). Perceived sleep quality was better than on placebo (SMD -0.41, 95% CI -0.82 to -0.00) and night awakenings were fewer (SMD -0.51, 95% CI -0.97 to -0.05), with no significant differences in sleep latency, total sleep time, or wake after sleep onset. Discontinuations for adverse events or for any cause did not differ.

Participants / model
Patients with insomnia in randomized placebo-controlled trials
Treatment
Oral trazodone versus placebo
Follow-up
not stated in the source
Study design
Systematic review and meta-analysis of 7 randomized placebo-controlled trials
Funding
not stated in the source

This analysis found no difference in discontinuations, unlike the 2024 meta-analysis of 44 trials.

Read the original source
2024 meta-analysis: 44 trials, 3,935 participants, adverse-effect dropouts RR 2.30

Systematic review and meta-analysis

Kokkali M et al. CNS Drugs. 2024;38(10):753-769. PMID 39123094.

Across 44 randomized trials (3,935 participants), trazodone compared with placebo for at least 5 days did not change subjective total sleep time (WMD 0.73 minutes, 95% CI -24.62 to 26.07). It improved sleep quality (SMD -0.58, 95% CI -0.87 to -0.28), reduced night awakenings (SMD -0.57, 95% CI -0.85 to -0.30) and wake after sleep onset (WMD -13.47 minutes, 95% CI -23.09 to -3.86), and lengthened polysomnographic total sleep time (WMD 27.98 minutes, 95% CI 4.02 to 51.95). The authors describe only minor effects on sleep latency, sleep efficiency, and daytime impairment. Adverse effects overall (RR 1.18, 95% CI 1.03 to 1.33) and dropouts due to adverse effects (RR 2.30, 95% CI 1.45 to 3.64) were more frequent than on placebo.

Participants / model
Participants with sleep disturbances across diagnoses in randomized trials
Treatment
Oral trazodone versus placebo for at least 5 days
Follow-up
At least 5 days of treatment per trial
Study design
Systematic review and meta-analysis of 44 randomized trials
Funding
not stated in the source

The population spans several diagnoses, not only primary insomnia.

Read the original source
AASM guideline: suggests against trazodone for insomnia (weak recommendation)

Systematic review and meta-analysis

Sateia MJ et al. J Clin Sleep Med. 2017;13(2):307-349. PMID 27998379.

The guideline suggests that clinicians not use trazodone for sleep onset or sleep maintenance insomnia in adults, compared with no treatment. It is a weak recommendation under GRADE, which the guideline says reflects lower certainty and should not be read as showing the drug is ineffective.

Participants / model
Adults with chronic insomnia
Treatment
Oral trazodone
Follow-up
not stated in the source
Study design
Clinical practice guideline (GRADE) based on a systematic review of randomized trials
Funding
not stated in the source

A guideline recommendation, not a trial. The guideline states a weak recommendation reflects lower certainty.

Read the original source
Caffeine model: 12 healthy men, one night, trazodone 100 mg

Randomized controlled trial

Paterson LM et al. J Psychopharmacol. 2009;23(5):487-94. PMID 19351801.

In 12 healthy men, 150 mg of caffeine at bedtime delayed sleep onset and reduced total sleep time and sleep efficiency. Adding 100 mg trazodone attenuated the drops in sleep efficiency and total sleep time, increased stage 3 sleep, and reduced awakenings.

Participants / model
12 healthy men
Treatment
Single bedtime oral dose of trazodone 100 mg with caffeine 150 mg
Follow-up
One night
Study design
Double-blind randomized crossover study with home polysomnography and sleep EEG
Funding
not stated in the source

This one-night caffeine model is the closest record to the stimulant claim. It did not test amphetamines, cocaine, repeated stimulant use, or training-related sleep loss.

Read the original source
After alcohol detoxification: 173 adults, 12 weeks, more drinking after stopping

Randomized controlled trial

Friedmann PD et al. Alcohol Clin Exp Res. 2008;32(9):1652-60. PMID 18616688.

Trazodone improved Pittsburgh Sleep Quality Index scores during treatment (mean change -3.02, 95% CI -3.38 to -2.67), but sleep quality matched placebo after it was stopped. The trazodone group had less improvement in the proportion of days abstinent during treatment (mean change -0.12, 95% CI -0.15 to -0.09) and more drinks per drinking day after stopping (mean change 4.6, 95% CI 2.1 to 7.1).

Participants / model
173 adults after alcohol detoxification who reported sleep disturbance (88 trazodone, 85 placebo)
Treatment
Oral trazodone 50 to 150 mg at bedtime, or placebo
Follow-up
12 weeks of treatment, outcomes over 6 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

This trial reported drinking outcomes, and the trazodone group did worse on them. It did not enroll stimulant users.

Read the original source
Methadone maintenance: 137 adults, no sleep improvement

Randomized controlled trial

Stein MD et al. Drug Alcohol Depend. 2012;120(1-3):65-73. PMID 21798674.

Trazodone did not improve subjective or polysomnographic sleep: without correction for multiple comparisons, 1 of 21 sleep measures differed, the 6-month effect on the Pittsburgh Sleep Quality Index was not significant (p = .10), and illicit drug use did not change.

Participants / model
137 adults on methadone maintenance with a PSQI score of 6 or higher
Treatment
Oral trazodone versus placebo
Follow-up
6-month outcome
Study design
Randomized placebo-controlled trial with two-night home polysomnography
Funding
not stated in the source

The population was adults on methadone maintenance, not stimulant users.

Read the original source
Nursing-home cohort: 7,791 matched pairs, fall injury 5.7% versus 6.0%

Human study

Bronskill SE et al. J Am Geriatr Soc. 2018;66(10):1963-1971. PMID 30247773.

The 90-day cumulative incidence of a fall-related injury leading to an emergency department visit or hospital admission was 5.7% after starting low-dose trazodone and 6.0% after starting a benzodiazepine (hazard ratio 0.94, 95% CI 0.83 to 1.08). Low-dose trazodone was no safer than benzodiazepines for fall injuries.

Participants / model
Nursing-home residents aged 66 and older in Ontario, Canada (7,791 matched pairs)
Treatment
Newly dispensed low-dose oral trazodone versus benzodiazepines
Follow-up
90-day follow-up
Study design
Population-based matched cohort study
Funding
not stated in the source

Observational data in older nursing-home residents. It does not describe younger adults.

Read the original source
FAERS priapism: 1,233 reports, trazodone PRR 9.04

Human study

Schifano N et al. Int J Impot Res. 2024;36(1):50-54. PMID 35597798.

1,233 priapism reports were identified. Among drugs with at least 30 reports, trazodone, olanzapine, and tadalafil showed disproportionate reporting, with proportional reporting ratios of 9.04 (95% CI 7.73 to 10.58), 1.55, and 1.42. Spontaneous reports show a signal, not an incidence rate.

Participants / model
Spontaneous adverse-event reports in the US FDA database
Treatment
Not formulation-specific
Follow-up
Reports from 2015 to 2020
Study design
Pharmacovigilance disproportionality analysis
Funding
not stated in the source

A reporting signal, not an incidence rate. Priapism incidence for trazodone is not established by this source.

Read the original source
PubChem: trazodone and trazodone hydrochloride identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 5533 (trazodone) and CID 62935 (trazodone hydrochloride).

Trazodone base: CID 5533, C19H22ClN5O, 371.9 g/mol, CAS 19794-93-5. Trazodone hydrochloride, the salt in US products: CID 62935, C19H23Cl2N5O, 408.3 g/mol, CAS 25332-39-2 (PubChem also lists 19666-36-5). US tablet and oral-solution strengths are stated as trazodone hydrochloride.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

Why is Trazodone in A tier?

A fits an FDA-approved medicine, approved for major depressive disorder since 1981, that is widely used off-label for sleep. Pooled insomnia trials show modest gains and more adverse effects and dropouts than placebo, and the sleep medicine guideline suggests against it for insomnia. The grade does not cover the supplier's stimulant and training claim, which no trial found tests.