![]() This narrative review provides an update on recent clinical data for trazodone in MDD and its place in current treatment strategies for MDD, with a focus on the once-daily trazodone Contramid ® formulation, and symptoms that do not respond well to other treatments. Difficult-to-treat depression (DTD) is a related concept describing “depression that continues to cause significant burden despite usual treatment efforts. Patients who fail to achieve remission after adequate trials with two or more different antidepressants have been described as treatment-resistant. Patients who require a longer treatment duration to achieve remission are at higher risk of early relapse. This low success rate may be due to a lack of adequate treatment, or low treatment adherence. Antidepressant therapy, with the goal of achieving remission of symptoms and recovery of function is the most common treatment for severe depression however, these goals are achieved in only about half of patients, and many experience relapses before recovery is achieved. ![]() Treatment can include psychotherapy, psychopharmacotherapy, or combinations of these. Major depressive disorder (MDD) is the most common mood disorder and a leading cause of disability worldwide, affecting multiple functional domains that impact education, work productivity, and quality of life (QoL). 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. 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 most common adverse effects of trazodone are somnolence, headache, dizziness and xerostomia. ![]() This, combined with a low incidence of weight gain, and sexual dysfunction, may improve adherence to treatment. ![]() 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. ![]() 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. 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. Major depressive disorder (MDD) is the most common mood disorder and a leading cause of disability worldwide. ![]()
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