Suvorexant in the Management Comorbid Sleep Disorder and Alcohol Dependence

Study Procedures Baseline On Day 1, prior to commencement of treatment baseline data will be collected on demographics, ISI questionnaire plus 2 short questions 1) how many hours sleep has the participant had for the past week; 2) how would the participant rate their sleep quality in the past week. The investigators will also determine previous drug use history, physical examination, urine drug screen and measures of alcohol dependence severity, psychological and social functioning (ATOPv7).

Treatment Period Treatment will begin immediately after collection of Baseline data. Suvorexant will not be given if breath alcohol concentration is above zero. Both groups will be treated using the St Vincent's Hospital standard protocol for management of alcohol withdrawal, in which benzodiazepines are provided as required according to the symptoms listed in the Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). That is, if the CIWA-Ar score is > 10 then benzodiazepines (BZD) are administered. Note, BZD will not be given for management of insomnia. Physicians involved in patient care, nurses and participants will be blinded to treatment assignment. Participants will be monitored for signs of adverse events (i.e. distress, significant alcohol withdrawal, and adverse response to suvorexant) approximately 4 hourly for the first 24 - 48 hrs of residential stay and then according to clinical assessment. All clinical observations will be made by a suitably qualified and experienced medical professional. Where any adverse events are observed, monitoring will be increased to meet clinical needs and treatment discontinued if required. Alcohol withdrawal severity will be assessed using the Clinical Institute Withdrawal Assessment - Alcohol revised (CIWA-Ar).

Note, during in-patient assessment there will be no consumption of alcohol (7-10 days). Upon release to outpatients the investigators will advise participants not to consume alcohol and will provide follow-up support to help maintain abstinence. If patients resume heavy drinking and are deemed to have relapsed i.e. daily alcohol consumption greater than 5 standard drinks each day, the investigators will tell them to cease the medication and they will be withdrawn from the study. Data collected to this point will be included in the study.

Follow-up Treatment Subsequent follow-up would occur weekly for 4 weeks post inpatient treatment and then every 4 weeks to week 25. Patients will continue the same dose of Suvorexant/placebo for the duration of the follow-up period. At the end of the 25 week trial patients will continue to receive treatment as usual. If they wish to continue to receive suvorexant they can get a prescription from their GP (suvorexant has been added to the pharmaceutical benefits scheme).

Data Collection Baseline

• Name, date of birth, gender, contact details.
• ISI Insomnia Severity Index questionnaire (modified)
• Substance use history, medical history including current medications.
• Psychosocial status (data routinely collected through national minimum data set)
• Past history withdrawal symptoms ("delirium tremens", "seizures" etc)
• DSM 5 criteria for alcohol use disorder (AUD)
• Structured clinical Interview for DSm-5 (SCID-5)
• Pittsburgh Sleep Quality Index (PSQI)
• Epworth Sleepiness Scale
• K10 (Kessler Psychological Distress Scale), 10 questions about psychological distress symptoms: baseline and daily while in alcohol withdrawal then at monthly follow up
• ATOP Australian Treatment Outcome Profile
• Breath alcohol reading
• Liver function test
• Urine drug screen

In-patient withdrawal:

• Actigraphy measures of sleep patterns (Externally worn non-invasive accelerometer and light exposure recorder worn continually, from the first day of admission to discharge).
• Portable Polysomnography (Multichannel recoding of the electrophysiological markers of sleep). Polysomnography (PSG) records brain activity, eye movements and muscle tone to identify stages of sleep. In addition leg movements, heart rhythm, pulse rate, oxygen saturation, nasal breath flow, snore and chest movements are used to identify respiratory activity and lower leg muscle activity is also monitored for disturbing movements. (Day 1 and Day 7)
• Epworth Sleepiness Scale (excessive daytime sleepiness)
• Sleep diary during their stay (seven-ten days)
• ISI Insomnia questionnaire (Day 7 only)
• Clinical Information (as per open ended questioning for all AE's)
• CIWA-Ar (revised Clinical Institute Withdrawal Assessment for Alcohol scale), 10-item assessment of severity of alcohol withdrawal: baseline and every 2 - 4 hours, performed by trained staff
• Craving for alcohol using Obsessive Compulsive Drinking Scale
• Kessler 10 measure of psychological distress (Day 7 last 3 days)

At weekly follow-up, for weeks 2 to 5 and at monthly follow-up from week 9 to 25

• Pittsburgh Sleep Quality Index (sleep quality) (Wk5,9,13,17,21,25)
• Epworth Sleepiness Scale on admission (excessive daytime sleepiness)
• Sleep diary \& ISI insomnia questionnaire
• Additional 2 short questions will be collected:
• how many hours sleep has the participant had for the past week;
• how would the participant rate their sleep quality in the past week;
• Clinical Information (as per open ended questioning for SAE safety data suvorexant form)
• Alcohol and other substance use (self report)
• ATOP Australian Treatment Outcome Profile (Wk5,9,13,17,21,25)
• K10 (Kessler Psychological Distress Scale)
• Breath alcohol reading
• Urine drug screen
• Liver/renal function tests (Wk 2,5,9,13,17,21,25)
• Craving for alcohol using Obsessive Compulsive Drinking Scale

Any differences between objective and subjective sleep measures will be documented and reflected back to patients on an individual basis. During the consent process all patients will be informed that this is a trial and that there will be no additional (other than the trial) medication provided for insomnia.