Lemborexant for the Treatment of Residual Insomnia in Major Depressive Disorder (MDD)

Exclusion Criteria27

• Have taken or participated in any clinical trial of lemborexant and other drugs with the same mechanism (e.g., daridorexant), regardless of treatment outcome;
• Have any known sensitivity to lemborexant or their excipients;
• A lifetime history (current or previous) of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or psychotic symptoms as determined by the MINI;
• Women who are pregnant or lactating (documented by a positive beta-human chorionic gonadotropin \[beta-hCG\] or human chorionic gonadotropin \[hCG\] urine test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG or hCG);
• Women who are not using an approved and effective method of contraception or family planning during the study. For example, combined estrogen- and progestogen-containing hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion and ligation, vasectomized partner, sexual abstinence, or two forms of contraception with any barrier method or oral hormones (ie.g., condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom).
• Positive toxicology screening results;
• If participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions or the therapeutic focus 4 weeks before screening and the entire duration of participation;
• Have active suicidal intent as determined by a score of 3 (severe suicidality with a clear plan and/or intent) or 4 (very severe: suicidal attempts) on item #3 on the HAM-D-17;
• Have had a course of electroconvulsive therapy or intravenous ketamine therapy in the current episode or any previous episode;
• Medical history of insomnia associated with another sleep disorder or any condition known to impact sleep. This includes any lifetime diagnosis of sleep-related breathing disorder, periodic limb movement disorder, restless legs syndrome, nightmare disorder, sleep terror disorder, sleepwalking disorder, rapid eye movement (REM) behaviour disorder, narcolepsy, or comorbid nocturia that is causing or exacerbating insomnia;
• STOP-Bang5 scores ≥ 5; International Restless Legs Scale (IRLS)6 scores ≥ 16,Epworth Sleepiness Scale (ESS)⁷ ≥ 11
• Habitual naps 4 or more days a week, occurring in the late afternoon or evening;
• Transmeridian travel across more than 3 time zones in the 2 weeks before screening, or between screening and study baseline, or plans to travel across more than 3 time zones during the study;
• Used any modality of treatment for insomnia, including cognitive-behavioural therapy within 2 weeks before screening;
• Excessive caffeine use, defined as consuming more than 400 mg of caffeine per day (approximately 4 cups of brewed coffee), or habitual consumption of caffeine after 6:00 p.m., which in the investigator's opinion may contribute to insomnia;
• Reports habitually consuming more than 14 drinks containing alcohol per week (females) or more than 21 drinks containing alcohol per week (males);
• Used prohibited prescriptions or over-the-counter concomitant medications, or used any medication or sleep aid with known effects on sleep within 2 weeks before screening;
• Report a history of sleep-related violent behaviour, or sleep driving, or any other complex sleep-related behaviour (e.g., making phone calls, preparing and eating food);
• Diagnosis of substance dependence or abuse within the last 3 months as determined by MINI3;
• Have a concomitant major unstable medical illness, cardiac pacemaker, or implanted medication pump;
• Have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except a febrile seizure of infancy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than 5 minutes;
• A history of risk factors for Torsade de Pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome) or the use of concomitant medications that prolonged the QTcF interval;
• Scheduled for major surgery during the study;
• Have a clinical finding that is unstable or that, in the opinion of the investigator(s), would be negatively affected by the study medication or that would affect the study medication (e.g., diabetes mellitus, hypertension, unstable angina);
• Have uncorrected hypothyroidism or hyperthyroidism. Subjects needing a thyroid hormone supplement to treat hypothyroidism must have been on a stable dose of the medication for 30 days prior to enrolment;
• Have any other condition that, in the opinion of the investigator(s), would adversely affect the subject's ability to complete the study or its measures.
• Non-English-speaking individuals because the ability to communicate study information, answer questions accurately and completely about the study, and obtain consent are necessary.