Clinical Research Directory

Inclusion Criteria: * Signed informed consent prior to participation * Outpatients aged 19-65 years * Diagnosis of Major Depressive Disorder (MDD) per DSM-5 using MINI; psychotic features allowed * Current major depressive episode lasting ≥8 weeks at baseline * MADRS total score ≥24 at both screening and baseline * CGI-S score ≥4 at both screening and baseline * Documented history of antidepressant treatment (ADT) with inadequate response (\<50% improvement), confirmed by ATRQ * Currently on one of the allowed antidepressants (SSRI: citalopram, escitalopram, fluoxetine, paroxetine, sertraline; SNRI: duloxetine, venlafaxine, desvenlafaxine, milnacipran; Others: bupropion, vortioxetine, amitriptyline, tianeptine, agomelatine) at minimum effective dose for ≥6 weeks * Agreement to maintain the same background ADT regimen until study completion * BMI between 16-40 kg/m² * Willingness to discontinue prohibited psychotropic medications during washout * Stable doses of permitted concomitant medications (oral hypoglycemics ≥30 days, thyroid replacement ≥90 days, antihypertensives ≥30 days, lipid-lowering agents ≥30 days before baseline) Exclusion Criteria: * Lifetime diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or other psychotic disorders * Diagnosis within past 6 months of panic disorder, generalized anxiety disorder, OCD, PTSD, eating disorder, substance abuse/dependence (except caffeine/nicotine), or clinically significant personality disorder * ≥25% reduction in MADRS score between screening and baseline * Significant suicide risk (per C-SSRS, MADRS item 10 ≥5, recent suicide attempt, or investigator judgment) * First major depressive episode onset after age 60 * Treatment resistance: ≥3 adequate ADT trials without remission, or non-response to antipsychotic augmentation * Prior ECT, VNS, rTMS within 5 years or history of ECT failure * Known hypersensitivity to lurasidone or excipients * Use of prohibited medications (strong CYP3A4 inhibitors/inducers, QTc-prolonging drugs) within 14 days before randomization * Prior exposure to lurasidone or investigational CNS drugs (per protocol limits) * Pregnancy, breastfeeding, or unwillingness to use effective contraception; positive pregnancy test at screening or baseline * Clinically significant ECG abnormalities (QTcB ≥460 ms in men, ≥480 ms in women) * Clinically significant lab abnormalities: ALT/AST \>2× ULN, bilirubin \>1.5× ULN, Hb \<8 g/dL (women) or \<9 g/dL (men), ANC \<1,200/µL, HbA1c \>8%, HBsAg or HCV antibody positive (unless HCV RNA negative), CrCl \<50 mL/min, abnormal thyroid function (TSH, free T3/T4) * History of serious medical conditions: uncontrolled cardiovascular disease, recent MI, arrhythmia, active cancer (within 5 years, except basal/squamous cell skin cancer), GI surgery affecting absorption, uncontrolled endocrine disease, moderate/severe hepatic impairment, untreated sleep apnea, seizure disorders, dementia, HIV infection * Prolactin \>100 ng/mL or pituitary adenoma history * Investigator/site staff or family members of study personnel * Inability to comply with study procedures or anticipated relocation during study * More than 2 prior attempts at screening/washout for this study