CNA/
Articles/
2508001123
  • Open Access
  • Article
Intravenous vs. Oral Trazodone in the Management of Withdrawal Symptoms in Psychiatric Inpatients: A Naturalistic Study
  • Miriam Olivola 1, 2, *,   
  • Filippo Mazzoni 1, 3,   
  • Tiziano Prodi 2, 4,   
  • Giada Versaci 2, 4,   
  • Giovanni Carnevale Miacca 1, 3,   
  • Alessandro Guffanti 1, 3,   
  • Vassilis Martiadis 5,   
  • Natascia Brondino 1, 2,   
  • Benardo Maria Dell’Osso 2, 4, 6, 7

Received: 09 May 2025 | Revised: 14 Jul 2025 | Accepted: 06 Aug 2025 | Published: 15 Aug 2025

Abstract

Background: Trazodone, a serotonin antagonist and reuptake inhibitor (SARI), is frequently used off-label in psychiatric settings to manage insomnia, agitation, and withdrawal symptoms in patients with Substance Use Disorders (SUD). While the oral formulation is widely adopted, intravenous (IV) trazodone may provide faster onset, better tolerability, and greater clinical efficacy in acute care. Methods: This naturalistic observational study compared the short-term efficacy and safety of oral versus IV trazodone in 100 psychiatric inpatients with a primary DSM-5-TR diagnosis of SUD, including alcohol, benzodiazepines, opioids, cocaine, or polysubstance use. Patients were consecutively admitted to the SPDC of Pavia between January and October 2024. Fifty patients received oral trazodone (up to 300 mg/day), and fifty received IV trazodone (50 mg TID, totaling 150 mg/day) for a minimum of five days. Efficacy was evaluated using the Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA-Ar) and a Visual Analogue Scale (VAS) for craving. Tolerability and safety were assessed with the UKU Side Effect Rating Scale and systematic monitoring of blood pressure and QTc intervals. Results: IV trazodone was associated with a significantly greater reduction in withdrawal symptoms (CIWA-Ar mean Δ: 14.8 vs. 9.2; p < 0.001), as well as stronger craving reduction (p = 0.017), and a higher rate of clinically significant improvement (86% vs. 62%; p = 0.012). The IV group also showed fewer adverse effects, including lower incidence of sedation (p = 0.028) and orthostatic hypotension (p = 0.041). No clinically relevant QTc prolongation was observed in either group. Conclusions: IV trazodone demonstrated superior efficacy and tolerability compared to its oral formulation for the short-term management of SUD-related withdrawal symptoms. These findings support its potential use as a viable alternative in acute psychiatric care, particularly when rapid stabilization is required and benzodiazepine use is limited or contraindicated.

References 

  • 1.
    Chiappini, S.; Cavallotto, C.; Mosca, A.; et al. Investigating the Effectiveness of Brexpiprazole in Subjects with Schizophrenia Spectrum Illness and Co-Occurring Substance Use Disorder: A Prospective, Multicentric, Real-World Study. Pharmaceuticals 2024, 17, 535. https://doi.org/10.3390/ph17040535.
  • 2.
    Cavallotto, C.; Chiappini, S.; Mosca, A.; et al. Examining Lurasidone Efficacy in Patients with Schizophrenia Spectrum Illness and Concurrent Alcohol and Substance Use Disorder: A Prospective, Multicentric, Real-World Investigation. J. Clin. Med. 2024, 13, 2206. https://doi.org/10.3390/jcm13082206.
  • 3.
    Saitz, R.; Mayo-Smith, M.F.; Roberts, M.S.; et al. Individualized treatment for alcohol withdrawal: A randomized double-blind controlled trial. JAMA 1994, 272, 519–523.
  • 4.
    Kosten, T.R.; O’Connor, P.G. Management of drug and alcohol withdrawal. N. Engl. J. Med. 2003, 348, 1786–1795.
  • 5.
    Mendelson, W.B. A review of the evidence for the efficacy and safety of trazodone in insomnia. J. Clin. Psychiatry 2005, 66, 469–476.
  • 6.
    Khouzam, H.R. Trazodone: An old drug with new uses. Postgradate Med. J. 2007, 119, 79–85.
  • 7.
    Stahl, S.M. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications; Cambridge University Press: Cambridge, UK, 2021.
  • 8.
    McElroy, S.L.; Keck, P.E., Jr. Pharmacologic agents for the treatment of substance use disorders. Psychiatr. Clin. N. Am. 2005, 28, 541–558.
  • 9.
    Guaiana, G.; Barbui, C.; Cipriani, A. Trazodone for depression. Cochrane Database Syst. Rev. 2010, 11, CD006234.
  • 10.
    Ruan, C.J.; Zhu, X. Intravenous formulations of antidepressants: Current status and future directions. CNS Drugs 2020, 34, 555–564.
  • 11.
    Martinotti, G.; di Giannantonio, M. Trazodone for substance abuse and sleep disorders. CNS Spectr. 2007, 12, 424–429.
  • 12.
    Basterzi, A.D.; Aydemir, C.; Kisa, C.; et al. Effects of trazodone on sleep quality and daytime sleepiness in alcohol-dependent patients. Prog. Neuropsychopharmacol. Biol. Psychiatry 2013, 40, 250–255.
  • 13.
    Tamburin, S.; Battisti, C.; Crespi, G.; et al. Trazodone and withdrawal symptoms: Evidence from case reports. Subst. Use Misuse 2011, 46, 1064–1070.
Share this article:
Download PDF
DOI
10.53941/cna.2025.100005
Issue
Volume 1, Issue 1
How to Cite
Olivola, M.; Mazzoni, F.; Prodi, T.; Versaci, G.; Miacca, G. C.; Guffanti, A.; Martiadis, V.; Brondino, N.; Dell’Osso, B. M. Intravenous vs. Oral Trazodone in the Management of Withdrawal Symptoms in Psychiatric Inpatients: A Naturalistic Study. Clinical Neuropsychopharmacology and Addiction 2025, 1 (1), 5. https://doi.org/10.53941/cna.2025.100005.
RIS
BibTex
Copyright & License
article copyright Image
Copyright (c) 2025 by the authors.