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Trz3.8
Trazodone Research
Mostly mechanism / observational
31 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most Trazodone studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2011–2026 with a typical study size of 98 participants.
Based on 31 studies · 9 meta-analyses · 4 RCTs · 90,931 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
Mostly mechanism / observational14 studies
Therapeutic & clinical
Mostly mechanism / observational12 studies
Depression & mood
Mostly mechanism / observational11 studies
Safety profile
Mostly mechanism / observational7 studies
Cognitive function
Mostly mechanism / observational5 studies
Anxiety & stress
Mostly mechanism / observational4 studies
Heart & blood pressure
Too few graded studies2 studies
Women's health
Too few graded studies2 studies
4 more outcomes with fewer studies not shown.
Active research area
22 studies in the last 5 years · Latest meta-analysis: 2026
201120182026
1Meta-Analysis2022
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: Clinicians should prioritize risk stratification and consider trazodone for patients requiring rapid symptom relief while integrating non-pharmacological interventions for long-term management.
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).
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: Conclusions 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: 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.
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: Further high-quality research is necessary to better define the therapeutic potential of trazodone in the management of neurological conditions.
Verrienti G, Lombardozzi G, Albergo G, De Filippis S. · International journal of psychiatry in clinical practice (2026)
Conclusions Despite being an older antidepressant, trazodone remains widely prescribed.
Beyond treating depression in neurological patients, it may may be useful in the treatment of some neurological aspects.
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: Future studies should involve larger, high-quality trials with unified methodologies to strengthen the reliability of conclusions.
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%).
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: 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: Since our findings are mostly based on post-hoc analyses, the evidence remains preliminary, highlighting the need for further research to produce more conclusive evidence.
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: Larger clinical studies are needed to confirm that CYP2D6 genotyping could contribute to preventing ADRs in clinical practice.
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.
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.
In plain English: Finally, we will summarize the endophenotypes responsive to trazodone and atomoxetine and highlight the role of these agents in the management of OSA and its consequences, especially in underserved areas.
Zafari R, Shahbazi M, Amirifard H, Najafi A. · Sleep & breathing = Schlaf & Atmung (2026)
Although standard treatments are available for OSA, the world does not have equal access to the best management approaches for OSA, which could be due to limited financial resources or a limited trained workforce.
Pharmacological agents, if selected wisely based on the endophenotypes of OSA, may offer an appropriate approach for selective cases of OSA who refuse standard treatments or do not have access to the standard care.
This review describes different OSA comorbidities, phenotypes, and endotypes of OSA and the role of trazodone and atomoxetine in the management of them.
Aishah A, Kim M, Gell L, Vena D, Azarbarzin A, Pho H, Norman D, Ojile J, Esmaeili N, Taranto-Montemurro L, Wellman A, Sands S, Messineo L. · Thorax (2025)
Mixed-model analyses compared the effect of vilo-trazo versus placebo on AHI 4 (apnoea-hypopnoea index with 4% desaturations; primary outcome) and hypoxic burden (secondary outcome).
In plain English: There was no significant improvement for trazodone in SE% (SMD = 0.09, 95% CI -0.19 to 0.38, P = 0.53); patients receiving trazodone perceived better sleep quality than those receiving placebo (SMD = -0.41, 95% CI -0.82 to -0.00, P = 0.05).
Seven randomised placebo-controlled trials involving only 429 patients in total — the entire dedicated meta-analytic base for trazodone in insomnia
NO significant improvement in sleep efficiency (SMD 0.09, 95% CI -0.19 to 0.38, P = 0.53), and no significant difference from placebo in sleep latency, total sleep time, or wake time after sleep onset
Significant reduction only in the number of awakenings (SMD -0.51, 95% CI -0.97 to -0.05) and a borderline improvement in self-reported sleep quality (P = 0.05)