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Trz3.8
Trazodone Research
Too few graded studies
36 peer-reviewed studies
What the evidence says
Too few graded studies
Trazodone doesn't have enough studies with structured effect-size data yet to pool a verdict. Browse the studies below for individual findings.
Most evidence is from high-quality meta-analyses and randomised trials published 2011–2026 with a typical study size of 30 participants.
Based on 36 studies · 11 meta-analyses · 5 RCTs · 8,982 total participants
Confidence
High confidence
By outcome
Sleep & insomniaThe strongest (and still modest) signal: meta-analysis found significantly fewer awakenings on trazodone, and polysomnography in primary insomniacs showed fewer night-time awakenings — but no significant change in wake-after-sleep-onset or total sleep time, and the AASM guideline recommends against this use · 1-7 nights · In a 7-night crossover in 16 primary insomniacs, slow-wave sleep was greater than placebo on day 7, and Stage 1 sleep was lower across test days (day 1 showed no slow-wave difference). A single very small study — not a replicated finding · About 1 week · Essentially none on the evidence: the trazodone insomnia meta-analysis found NO significant difference from placebo in sleep latency, and the AASM guideline specifically suggests clinicians not use trazodone for sleep-onset insomnia · Not demonstrated
Too few graded studies15 studies
Depression & mood
Too few graded studies15 studies
Therapeutic & clinical
Too few graded studies15 studies
Safety profile
Too few graded studies10 studies
Cognitive function
Too few graded studies5 studies
Anxiety & stress
Mostly mechanism / observational4 studies
Heart & blood pressure
Mostly mechanism / observational4 studies
Women's health
Too few graded studies2 studies
4 more outcomes with fewer studies not shown.
Active research area
27 studies in the last 5 years · Latest meta-analysis: 2026
201120182026
1Meta-Analysis2026
In plain English: The effect of specific antidepressants on QTc interval differed between adults with depression.
Ostinelli EG et al. · BMJ (Clinical research ed.) (2026)
Of 130 unique randomised controlled trials identified, 35 (27%) included individual level data (8679 participants) on QTc with placebo and 10 antidepressants (amitriptyline, bupropion, duloxetine, escitalopram, fluoxetine, mirtazapine, paroxetine, trazodone, venlafaxine, vortioxetine).
Compared with placebo, escitalopram and amitriptyline were associated with increased QTc intervals (8.7 milliseconds (ms), 95% credibility interval (CrI) 1.6 to 15.8, and 5.3 ms, 0.8 to 9.8, respectively).
When risk factors were considered, amitriptyline and escitalopram were also associated with the highest QTc prolongations (58.8% and 21.3%, respectively), whereas venlafaxine and vortioxetine were often associated with the lowest QTc intervals (24.1% and 9.7%, respectively).
In plain English: Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available.
De Crescenzo, D'Alò, Ostinelli, Ciabattini, Di Franco, Watanabe, Kurtulmus, Tomlinson, Mitrova, Foti, Del Giovane, Quested, Cowen, Barbui, Amato, Efthimiou, Cipriani · The Lancet (2022)
170 trials (36 interventions, 47,950 participants) in the systematic review; 154 double-blind RCTs (30 interventions, 44,089 participants) in the network meta-analysis
The agents found more efficacious than placebo for acute treatment were benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem and zopiclone (SMD 0.36-0.83) — trazodone was not among them
Trazodone is grouped with the licensed drugs carrying poor tolerability and/or absent long-term data
In plain English: Trazodone demonstrates robust efficacy for improving sleep and depressive symptoms in patients with comorbid insomnia and depression.
Hameed AK, Asiri M, Fedwi MM, Jawad M, Prahlad P, Singh A, Chauhan AS, Sahoo S, Singh M, Kadhem M. · Psychopharmacology (2026)
Data extraction, quality assessment using the Cochrane ROB2 tool, and meta-analysis were performed, utilizing the standardized mean difference (SMD) and odds ratios (ORs).
Trazodone significantly improved sleep quality (Pittsburgh Sleep Quality Index: SMD = -0.827, 95% CI: -1.331 to -0.323, p = 0.001) and reduced depression severity (Hamilton Depression Rating Scale: SMD = -0.365, 95% CI: -0.480 to -0.249, p < 0.001).
Clinical Global Impression scores showed non-significant trends favoring trazodone (SMD = -0.209, p = 0.118).
In plain English: Trazodone extends total sleep time but does not affect perceived sleep duration.
Kokkali M, Pinioti E, Lappas AS, Christodoulou N, Samara MT. · CNS drugs (2024)
When different units or scales were used, Hedge's adjusted g standardized mean difference (SMD) was calculated.
Trazodone did not significantly impact subjective total sleep time (TST) [WMD = 0.73 min, 95% confidence interval (CI) - 24.62; 26.07, p = 0.96] but improved sleep quality (SQ) (SMD = - 0.58, 95% CI - 0.87; - 0.28, p < 0.01) and secondary outcomes.
It may improve sleep quality and continuity but has minor effects on sleep latency, efficiency, and daytime impairment.
In plain English: In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84).
In plain English: Our findings indicate that selective serotonin reuptake inhibitors (SSRIs), dopamine agonists, and rTMS suggest relative efficacy and an acceptable safety profile in treating PD with depression.
Zhao Y, Mo Q, Liu Y, Chen X, Zhao Q, Wang H, Yan Z, Cao L, Zhao G. · Brain and behavior (2026)
Treatment effects were estimated using standardized mean differences (SMDs) for efficacy and odds ratios (ORs) for safety.
Compared with placebo, citalopram (SMD = -0.99, 95% CI: -1.87 to -0.12) and primary motor cortex (M1) repetitive transcranial magnetic stimulation (rTMS) (SMD = -1.29, 95% CI: -1.93 to -0.64) significantly improved depressive symptoms with moderate-quality evidence.
Several treatments could not be included in the safety network because of insufficient connectivity.
In plain English: For patients undergoing SAEs following the administration of antidepressants, trazodone, vortioxetine, vilazodone and agomelatine are alternative antidepressants.
Wang Q, Xu Z, Chen X, Liu L, Liu X. · Andrology (2025)
The incidences of EjD, erectile dysfunction (ED), decreased libido (DL), adverse events (AE), withdrawal due to adverse events (WDAE) and withdrawal due to lack of efficacy (WDLE) were pooled using odds ratio (OR) with their 95% confidence intervals (CI).
Clomipramine (OR 42.11, 95% CI [9.90, 179.08]), WS5570 (OR 28.99, 95% CI [1.48, 568.97]) and paroxetine (OR 18.63, 95% CI [9.33, 37.23]) had significant risk of EjD comparing to placebo.
Additionally, duloxetine (OR 7.37, 95% CI [2.61, 20.78]), clomipramine (OR 5.29, 95% CI [1.72, 16.25]), paroxetine (OR 3.75, 95% CI [1.37, 10.26]) and escitalopram (OR 3.04, 95% CI [1.20, 7.71]) presented higher risk of ED comparing to placebo.
In plain English: We suggest that clinicians not use trazodone as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK).
Sateia, Buysse, Krystal, Neubauer, Heald · Journal of Clinical Sleep Medicine (2017)
The AASM commissioned a task force of four sleep-medicine experts, ran a systematic review of randomised controlled trials, and graded the evidence with GRADE
Trazodone received a WEAK recommendation AGAINST use for both sleep-onset and sleep-maintenance insomnia — the same recommendation given to diphenhydramine, melatonin, tryptophan, valerian and tiagabine
By contrast the guideline suggests clinicians USE doxepin for sleep-maintenance insomnia and suvorexant, eszopiclone, zaleplon, zolpidem, triazolam, temazepam and ramelteon for their respective indications (all WEAK)
In plain English: The proposed algorithm may assist neurologists in the management of depression in patients with PD by providing specific recommendations on the role of trazodone across different clinical scenarios, allowing for individualized treatment.
Antonini A, Bentivoglio AR, Calandra-Buonaura G, Ceravolo R, Leta V, Pellecchia MT, Pilotto A, Nicoletti A. · Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology (2026)
In presence of depressive mood with predominant insomnia, high-dose trazodone should be considered along with mirtazapine.
In case of cognitive deficits with agitation, low to medium dose trazodone is suggested.
Conclusions The proposed algorithm may assist neurologists in the management of depression in patients with PD by providing specific recommendations on the role of trazodone across different clinical scenarios, allowing for individualized treatment.
In plain English: The emerging role of non-antidepressant agents (e.g., several opioids and antiparkinsonian drugs) as potential precipitants support tailored interprofessional medication review in poly-medicated subjects.
Blyzniuk B, Danukalo M, Gastaldon C, Barbui C, Toto S, Raschi E, Seifritz E, Kuzo N, Schoretsanitis G. · European journal of clinical pharmacology (2026)
Results A total of 764 cases were included; 653 (85.6%) and 496 (65.0%) met the Sternbach and the Hunter Criteria, respectively.
Patients with SS following suicide attempts were more frequently admitted to intensive care units with higher mortality rates than patients with SS related to regular prescriptions (79.4% vs 35.6% and 18.0% vs 5.1%, respectively, both p < 0.001).
Of 645 regular prescription cases, 92.9% were drug combinations (≥ 2 agents).
In plain English: All three medications significantly enhance subjective sleep perception and alleviate depressive symptoms.
Zhang X, Chen Y, Deng R, Tao S, Zou M, Wang Q. · Journal of affective disorders (2026)
Background and purpose Insomnia is a common symptom in depressive disorder, affecting up to 80% of those patients.
Results The PSG results showed that agomelatine may not significantly change percentage N1 of sleep period time (N1%) and Latency of REM sleep (L-REM).
Mirtazapine significantly increased total sleep time (TST), slow-wave sleep of sleep period time (SWS%), and sleep efficiency (SE%), while reducing percentage wake after sleep onset of sleep period time (WASO%).
In plain English: The review found no consistent evidence linking trazodone use during pregnancy to increased risks of congenital malformations, stillbirths, or low birth weight.
Glasgow-Osment B, Wahib F, Kassam S, Zanin M, Garcia-Bournissen F. · European journal of clinical pharmacology (2025)
However, some studies suggested a possible association with an increased risk of spontaneous and therapeutic abortions.
Given the limited and varied data, further research with larger, well-controlled studies are needed to establish the safety profile of trazodone during pregnancy.
Overall, clarifying the specific risks and benefits of trazodone use in pregnancy will better guide clinical decision-making and improve maternal-fetal health outcomes.
In plain English: Trazodone may improve objective sleep continuity and may be associated with changes in sleep architecture, including increased SWS and reduced N2 sleep, in patients with depression, without significantly altering REM sleep.
Meng L et al. · Frontiers in psychiatry (2026)
Regarding sleep architecture, trazodone was linked to reduced non-rapid eye movement sleep stage 2 (N2) proportion (MD = -9.09, 95% CI -16.60 to -1.59, P = 0.017) and increased slow wave sleep (SWS) proportion (MD = 8.05, 95% CI 3.42 to 12.68, P = 0.001).
No significant effects were observed for wake after sleep onset, NREM stage 1 percentage, rapid eye movement sleep percentage (REM), and REM sleep latency.
Trazodone may improve objective sleep continuity and may be associated with changes in sleep architecture, including increased SWS and reduced N2 sleep, in patients with depression, without significantly altering REM sleep.
In plain English: New use of low-dose trazodone was no safer with respect to a risk of a fall-related injury than new use of benzodiazepines.
Bronskill, Campitelli, Iaboni, Herrmann, Guan, Maclagan, Watt, Rochon, Morris, Jeffs, Bell, Maxwell · Journal of the American Geriatrics Society (2018)
Retrospective propensity-score-matched cohort of 7,791 Ontario nursing-home residents aged 66+ newly dispensed low-dose trazodone versus newly dispensed benzodiazepines
Cumulative incidence of hospitalisation for a fall-related injury within 90 days: 5.7% with low-dose trazodone vs 6.0% with benzodiazepines (hazard ratio 0.94, 95% CI 0.83-1.08)
Findings were consistent across sensitivity analyses restricted to hip or wrist fracture and at 30, 60 and 180 days of follow-up
In plain English: While antipsychotics are first options for MDE-MFS, their effect on manic symptoms in BD patients with MDE-MFS is still unclear.
Gao S, Chen Y, Liu J, Zhang Q, Zhao X, Liu B, Zhang Y, Li L, Wang G. · Psychological medicine (2025)
Effects were expressed as relative risk (RR) or standardized mean difference (SMD).
Results In patients with MDE-MFS, antipsychotics significantly improved depressive (RR = 1.46 [95% CI: 1.31, 1.61]) and manic (SMD = -0.35 [95% CI: -0.53, -0.17]) symptoms without increasing the risk of manic switch (RR = 0.91 [95% CI: 0.53, 1.55]).
For MDE-MFS in patients with major depressive disorder, trazodone has shown potential effectiveness in retrospective studies, while the effectiveness of antidepressants on BD patients with MDE-MFS lacked evidence.
In plain English: Our findings suggest that mCPP could contribute to trazodone-related ADRs, especially in individuals with reduced CYP2D6 metabolism.
Wiss FM, Krieg CD, Lampert ML, Meyer Zu Schwabedissen HE, Stäuble CK, Mikoteit T, Imboden C, Allemann SS. · Journal of clinical psychopharmacology (2026)
After accounting for phenoconversion and adjusting for sex, trazodone dose, and CYP3A5 phenotype, CYP2D6 poor metabolizers were found to be more likely to develop ADRs compared with normal metabolizers (OR: 8.96; 95% CI=1.67-48.08).
No association with ADRs was found for genetic variants in CYP3A5 and ABCB1 .
Subgroup analysis revealed that reduced CYP2D6 activity was associated with a higher mCPP-to-trazodone ratio and a greater tendency for ADRs.
In plain English: The results will help improve treatment strategies for managing sleep problems, fatigue, and daytime sleepiness in individuals with traumatic brain injury.
Gharooee Ahangar S, Hasanpour M, Fatahian R, Zarei P, Mehdizadeh H. · Trials (2026)
Discussion This study is one of the first to compare trazodone and melatonin alone and in combination for insomnia, fatigue, and daytime sleepiness in TBI patients.
The results will help improve treatment strategies for managing sleep problems, fatigue, and daytime sleepiness in individuals with traumatic brain injury.