Role of trazodone in treatment of major depressive disorder: an update

Abstract

Major depressive disorder (MDD) is the most common mood disorder and a leading cause of disability worldwide. Trazodone, a triazolopyridine serotonin receptor antagonist and reuptake inhibitor (SARI) antidepressant approved for major depressive disorder (MDD) in adults, has established efficacy that is comparable to other available antidepressants, and is effective for a range of depression symptoms, including insomnia, which is one of the most common and bothersome symptoms of depression. Also, trazodone’s pharmacodynamic properties allow it to avoid the side effects of insomnia, anxiety and sexual dysfunction often associated with selective serotonin reuptake inhibitor antidepressants. In this narrative review, we have summarized recent clinical trials and real-world data on trazodone, including the recently introduced once-daily formulation, which has single dose pharmacokinetic properties that maintain effective blood trazodone levels for 24 h, while avoiding concentration peaks associated with side effects. This, combined with a low incidence of weight gain, and sexual dysfunction, may improve adherence to treatment. The most common adverse effects of trazodone are somnolence, headache, dizziness and xerostomia. It has minimal anticholinergic activity but may be associated infrequently with orthostatic hypotension (especially in patients with cardiovascular disease or older adults), QT interval prolongation, cardiac arrhythmias, and rare episodes of priapism. The low liability for activating side effects, the efficacy on symptoms such as insomnia and psychomotor agitation and the rapid onset of action make it useful for many depressed patients, both in monotherapy at nominal dosages of 150–300 mg/day, and in combination with other antidepressants at lower dosages.

Connecting the Dots: Heart Failure and Insomnia

“…Trazodone is an antidepressant drug whose ability to enhance sleep is due to inhibiting serotonin 5-HT2 receptors, which increases the depth of sleep 34,35 . Trazodone may occasionally be linked to orthostatic hypotension, QT interval prolongation, and cardiac arrhythmias 36 . These effects could be particularly detrimental in patients with HF.…”

TED (Trazodone Effectiveness in Depression): effectiveness of trazodone extended-release in subjects with unsatisfactory response to SSRIs

“…Trazodon jest również antagonistą 5HT2 A/C, co zapobiega ograniczeniu przekaźnictwa noradrenergicznego i dopaminergicznego w korze przedczołowej z powodu zwiększonej stymulacji serotoninergicznej, co jest uważane za mechanizm wyjaśniający spłycenie emocjonalne i ograniczoną skuteczność SSRI w łagodzeniu anhedonii. Ponadto blokada 5HT2 A/C może zapobiegać wystąpieniu lub ograniczać nasilenie i ryzyko zaburzeń seksualnych wywołanych blokadą wychwytu serotoniny, a w połączeniu z antagonizmem receptorów H1 i α1 adrenergicznych promuje działanie nasenne i anksjolityczne trazodonu [14][15][16]. Jak pokazano w analizie pilotażu tego badania, trazodon XR wykazał się dobrym działaniem przeciwdepresyjnym w MDD, nie tylko w redukowaniu nasilenia objawów depresji, ale także przez poprawę anhedonii, funkcji seksualnych, snu i ogólnego funkcjonowania [17].…”

TED—trazodone effectiveness in depression: a naturalistic study of the effeciveness of trazodone in extended release formulation compared to SSRIs in patients with a major depressive disorder

“…It is approved by the European Medicines Agency (Europe) and the Food and Drug Administration (United States of America) for the treatment of MDD in adult patients. Recommendations for trazodone use in clinical practice suggest that trazodone is helpful in MDD comorbid with anxiety, insomnia, and in MDD with psychomotor agitation (Cuomo et al, 2019;Albert et al, 2023;Fagiolini et al, 2023). A number of trials were conducted to compare trazodone vs. other antidepressants.…”