Phase IV Open‑Label Study of Trazodone Hydrochloride for Emotional Blunting in Major Depressive Disorder Patients with Inadequate Response to Prior SSRI/SNRI Therapy

Primary objective: To assess the change in emotional blunting—the experience, expression, and regulation of positive and negative emotions—after 8 weeks of oral trazodone in patients with Major Depressive Disorder who have had an incomplete response to prior SSRI or SNRI therapy, addressing a residual symptom domain that limits functional recovery. Secondary objectives: – Evaluate the clinical course of depression over the 8‑week period. – Assess effects on cognitive function. – Measure changes in health‑related quality of life. – Determine impact on sleep quality. – Examine influence on work or school performance, social interactions, and family/home responsibilities.

The trial enrolled male and female outpatients of any ethnic origin between 18 and 65 years of age who met the diagnostic criteria for Major depressive disorder (single or recurrent) according to DSM‑5 and were experiencing a current depressive episode of less than 12 months duration. Participants were required to have a Montgomery‑Åsberg Depression Rating Scale (MADRS) total score ranging from 22 to 28 and an Oxford Depression Questionnaire (ODQ) score of at least 50 while receiving a minimum of six weeks of adequate-dose SSRI or SNRI monotherapy with an inadequate clinical response, indicating eligibility for a medication switch. General health status was limited to outpatient status without specifying additional comorbidities. Women of childbearing potential needed a negative pregnancy test at baseline and adherence to approved contraceptive methods throughout the early study period. The sponsor did not provide information on the total number of participants enrolled. Selection was based on the outlined inclusion criteria, and no additional lifestyle restrictions were specified.

The study is a Phase IV, open‑label, single‑arm investigation evaluating the efficacy of trazodone in patients with Major Depressive Disorder who have shown an inadequate response to prior SSRI/SNRI therapy. Participants undergo a screening visit to confirm eligibility, obtain written informed consent, and record baseline assessments including the Montgomery‑Åsberg Depression Rating Scale and the Oxford Depression Questionnaire (ODQ). At the baseline visit, trazodone treatment is initiated (75 mg or 150 mg prolonged‑release tablets) and dose titration is documented. Follow‑up visits are scheduled at weeks 2, 4, 6, and 8 to monitor safety, adherence, and changes in ODQ score, as well as secondary outcomes such as cognition, sleep, quality of life, and functional status. The final assessment occurs at the end‑of‑study visit (week 8), completing an 8‑week treatment period and approximately 10 weeks of total participant involvement including screening. Early termination may occur if a participant withdraws consent, experiences a serious adverse event, becomes pregnant, fails to comply with protocol requirements, or requires alternative therapeutic intervention. Recruitment is planned from 31 July 2026 to 30 September 2027.

The investigational product is a prolonged‑release oral tablet containing trazodone hydrochloride. Available strengths are 75 mg and 150 mg per tablet. The tablets are administered by the oral route once daily, with the dose selected according to the investigator’s assessment of the patient’s prior response to serotonergic agents. All study participants receive either the 75 mg or the 150 mg formulation throughout the 8‑week treatment period.

No placebo or active comparator is employed in this open‑label, Phase IV study. Participants continue any previously prescribed standard‑of‑care antidepressant therapy (e.g., SSRIs or SNRIs) that was deemed ineffective for complete response, as permitted by the protocol, while the investigational trazodone is added to the regimen.

Drug administration follows a fixed schedule with dosing occurring each morning after a light meal to enhance tolerability. Compliance is monitored by pill count at each study visit, patient‑reported dosing diaries, and periodic verification of plasma trazodone concentrations when required by the protocol. Missed doses are recorded, and participants are instructed to resume the prescribed regimen the following day without exceeding the assigned daily dose.

The primary efficacy assessment will be based on the change in the score of the Oxford Depression Questionnaire (ODQ) from baseline to the 8‑week visit. Participants will complete the questionnaire at the start of the study and again after 8 weeks of treatment; the difference between these two scores will constitute the primary outcome measure.

Secondary efficacy evaluations will include the assessment of depressive symptom severity, cognitive function, sleep quality, overall quality of life, and functional capacity in work, school, social, and family settings. These parameters will be measured using validated scales and questionnaires appropriate for each domain, administered at baseline and at the 8‑week assessment. Changes from baseline will be analyzed to determine the treatment effect on each secondary endpoint.