Study evaluating the efficacy and safety of daridorexant in patients with major depressive disorder and insomnia.

Prior treatment

• Concomitant Use with Moderate and potent CYP3A4 Inhibitors: Prohibited due to potential drug interaction (refer to protocol section 4.5 for specifics).
• Use of Non-Permitted Sleep Medications: Concurrent use of melatonin, benzodiazepines, sedative antidepressants or sedative antipsychotics use for insomnia not allowed by the protocol and unwillingness to follow the slow-taper schedule constitutes an exclusion criterion.
• No concurrent sleep medications at least 30 days prior to baseline. Exclusion criteria if the patient has withdrawal symptoms and/or sleep disturbances measured by BWSQ prior to baseline.

Other illness

• Other Current Psychiatric Disorders: Any current psychiatric disorder other than major depressive disorder (e.g., active psychotic disorders, mania, hypomania, acute schizophrenia, schizoaffective disorder).
• Moderate and severe hepatic Impairment: Any hepatic condition deemed unsafe for daridorexant use.
• Substance Use Disorder: History of substance use disorder without sustained remission. Exception: past sedative abuse may be permissible if remission criteria are clearly met, as determined by the investigator.
• Uncontrolled Severe Medical Conditions: Any condition that could interfere with study procedures, safety, or outcome measures (e.g., unstable cardiovascular, respiratory, neurological, or endocrine disorders).
• Hypersensitivity: Known allergy or hypersensitivity to daridorexant or any of its excipients.
• Specific Sleep Disorders: Sleep apnea or hypopnea index ≥ 15 events/hour (based on American Academy of Sleep Medicine criteria) or any event associated with oxygen saturation < 80% (as measured by polysomnography).
• Periodic limb movement index ≥ 15 events/hour (as measured by polysomnography). Restless legs syndrome, circadian rhythm sleep-wake disorders, REM behavior disorder, or narcolepsy.

Other

• Relapse or Worsening of the Main Diagnosis: Relapse of depression whose severity precludes continued participation according to the investigator’s judgment.
• Excessive Caffeine Intake: Daily consumption of >400 mg of caffeine (e.g., >4 standard cups of coffee).
• High-Risk Alcohol Consumption: Alcohol intake above recommended risk thresholds (i.e., >4 standard drinks/day for men, >2 standard drinks/day for women).
• Pregnancy or breastfeeding
• Cognitive Impairments: Significant impairments that prevent the comprehension or completion of study questionnaires or procedures.

• Age Range: 18-99 years old.
• Patients with a current major depressive episode according to DSM-5, in a stable phase (defined as at least 4 weeks without significant changes in antidepressant treatment and no psychiatric hospitalizations in the previous 8 weeks) and with moderate or greater severity, as indicated by a total score of ≥ 20 on the Montgomery–Åsberg Depression Rating Scale (MADRS).
• Insomnia disorder confirmed according to DSM-5
• Informed Consent: Ability and willingness to provide written informed consent.
• Acceptance of Protocol Requirements: Agreement to adhere to all scheduled visits, treatment plans, and study procedures.