Brexanolone to Target Concurrent PTSD and Stress Induced Alcohol Use in Veterans: A Dose Finding Study

Exclusion Criteria

• •1. Meets current DSM-5 diagnostic criteria for schizophrenia, bipolar disorder, and/or other severe mental illnesses, as defined by the QuickSCID-5 at intake. Please note that the QuickSCID-5 provides a Psychotic Symptom Screen. In the event, a patient screens positive for psychotic symptoms, the study team member will administer Modules B (Psychotic and Associated Symptoms) and C (Differential Diagnosis of Psychotic Disorders) from the Structured Clinician Interview for DSM-5 Clinician Version to determine a diagnosis of schizophrenia or another psychotic disorder.
• •2. Increased risk of suicide that necessitates inpatient treatment or warrants therapy excluded by the protocol, and/or a current suicidal plan, per investigator's clinical judgement during interview.
• •3. Treatment with trauma-focused therapy (e.g., Cognitive Processing Therapy, Prolonged Exposure Therapy, or Eye Movement Desensitization \& Reprocessing Therapy) for PTSD within two weeks of intake (if participant is receiving therapy, he/she must complete treatment prior to entering study). Note: Supportive psychotherapy in process at time of Screening may be continued.
• •4. Meets criteria for current diagnosis of moderate or severe non-alcohol substance use disorder (except for caffeine and nicotine), as measured via QuickSCID-5, during the preceding 1 month relative to intake, per PI discretion, based on participant's screening interview.
• •5. Tests positive for illicit substances during urine toxicology screens (except cannabis) at intake session. Patients who utilize cannabis but do not meet substance use disorder criteria are permitted.
• •6. Self-reported past 30-day use at intake of psychoactive drugs (except cannabis), including opioids, CNS depressants (such as benzodiazepines), use of psychotropic medications in the class of antipsychotics, mood stabilizers, or stimulants. Note: Participant use of stable doses (prescribed for \>2 months and the current dose has been stable or ≥3 weeks at intake) of antidepressants will be reviewed by Study MD.
• •7. Likely to exhibit clinically significant alcohol withdrawal during the study. Specifically, we will exclude subjects who a) have a history of perceptual distortions, seizures, delirium, or hallucinations upon withdrawal, assessed during physical examination as part of intake procedures or b) have a score of \> 8 on the Clinical Institute Withdrawal Assessment scale at intake appointment. Participants must have a CIWA-Ar score of \< 8 prior to randomization.
• •8. Any clinically significant, uncontrolled, or medical/surgical condition, that at the discretion of the investigator, would contraindicate use of brexanolone, or limit ability to complete study assessments, including end stage renal disease, significant arrhythmia or heart block, or heart failure, severe thrombocytopenia or hemophilia, severe hepatic failure, complete hearing loss, and/or need for surgery that might interfere with ability to participate. Such conditions will be assessed by the Study MD based upon physical examination (including review of medical history), as well as review of medical records, ECG and basic blood chemistries (i.e., CBC).
• •9. Females who are pregnant, nursing, planning to become pregnant or fail to use one of the following methods of birth control during study participation (unless she or her partner is surgically sterile, or she is postmenopausal). Birth control includes: hormonal contraceptives (oral, implant, injection, patch, or ring), contraceptive sponge, double barrier (diaphragm or condom plus spermicide) or IUD.
• •10. Any finding that, in the view of the principal investigator, would compromise the subject's ability to fulfill the study visit schedule or requirements.