Aim: This paper belongs to a series of three manuscripts examining the clinically relevant evidence about the use of trazodone in major depressive disorder (MDD). One of the papers provides general clinical guidance for the use of trazodone MDD. Another paper evaluates the clinically relevant evidence pertaining to the use of trazodone in MDD with insomnia, and the present manuscript evaluates the properties of prolonged release trazodone (T-RP) and trazodone once-a-day (T-OAD), to identify the characteristics of patients that may benefit from the use of one of the formulations.
Methods: PubMed and Cochrane Library were searched for English language papers by using combinations of the following key words: trazodone, once-a day, prolonged release, extended release, slow release. United States, European and Italian Medicine Agency prescribing information for trazodone were consulted as well.
Results: Trazodone is a multifunctional drug, characterized by different affinities for specific receptors and transporters. Clinical efficacy on specific symptoms is influenced by pharmacokinetic aspects and variables such as the dose and the formulation that is prescribed and taken. T-RP can be particularly useful in the treatment of patients with mild or moderate depression, who show sleep disturbance and/or moderate or severe anxiety symptoms and who can benefit - in particular periods of the day or night (e.g. in the phase of falling asleep or during periods of increased anxiety-agitation), of peak blood concentration, which are higher than those of T-OAD. T-OAD appears particularly indicated for patients with moderate or severe depression, who show mild or moderate sleep and/or anxiety disorders, who have late insomnia (insomnia in the final part of sleep, i.e. early morning awakening), and who can benefit from the possibility of starting the drug at a dose that is already potentially effective (150 mg) for depressive symptoms. This dose can be then increased to 300 mg, and prescribed in the evening and once a day, which potentially improves treatment adherence.
Discussion: The different formulations of trazodone allow a personalization of the treatment, which may be targeted to the specific needs of each patient.