Intervention: Suvorexant
Trial phase: Phase 4
ATC code: N05CJ01 | N05CM19
SMILES: [H][C@@]1(C)CCN(c2nc3cc(Cl)ccc3o2)CCN1C(=O)c1cc(C)ccc1-n1nccn1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 3
Group description: In this arm, subjects will receive 10 mg suvorexant 2 hours before a one-minute 35% CO2 challenge.

suvorexant
Eligibility criteria:
Inclusion Criteria:

They must be in stable physical health as determined by a medical evaluation, including physical examination, electrocardiogram, laboratory findings (comprehensive metabolic panel, complete blood count [CBC], free T4, urine pregnancy test, urinalysis), urine toxicology screen, and a negative urine pregnancy test in women of child-bearing potential.
They must satisfy the new clinical criteria in the Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) for a current principal diagnosis of PD as confirmed by a semi-structured, diagnostic interview, the Mini International Neuropsychiatric Interview (MINI), administered by the PI.
Since clinical depression (MDD) is associated with CSF ORX abnormalities, only patients with a current PD without MDD will be enrolled. They will also be required to have a current Montgomery-Asberg Depression Rating Scale (MADRS) total score <12.
They will be off all regular psychiatric medications and avoid drinking grapefruit juice for at least 2 weeks prior to the 35% CO2 test.
They must not be pregnant or breastfeeding a baby; and women of childbearing potential must be using birth control while on this study.

Exclusion Criteria:

any history of a psychotic disorder, bipolar disorder, MDD, depression not otherwise specified (NOS), obsessive compulsive disorder, an eating disorder, post-traumatic stress disorder, or generalized anxiety disorder
medical conditions for which suvorexant could be contraindicated, such as narcolepsy
any other sleep disorder
a substance use disorder, as defined by the DSM-5, within 6 months of the screening visit
ongoing use of psychiatric medications in the 2 weeks prior to the 35% CO2 test

current use of certain drugs, including

strong cytochrome P450 3A (CYP3A) inhibitors (such as ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin, and conivaptan);
moderate CYP3A inhibitors (such as amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil);
strong CYP3A inducers (such as rifampin, carbamazepine and phenytoin);
digoxin
history of any neurological disorder affecting the CNS
history of uncontrolled or serious medical illness
a history of hypersensitivity or allergy to suvorexant
pregnancy or lactation status, or unwillingness to use birth control while on this study, for women of child-bearing potential
compromised lung function (e.g., chronic obstructive pulmonary disease [COPD], emphysema, idiopathic pulmonary fibrosis, lung cancer)
inability to fast the required amount of time prior to study visit 2
a positive test for cannabinoids, opiates, benzodiazepines, amphetamines, cocaine and metabolites
out-of-range lab values
an abnormal EKG
a score > 12 on the Montgomery-Asberg Depression Rating Scale (MADRS)
inability or unwillingness to avoid drinking grapefruit juice for two weeks prior to the 35% CO2 challenge test
a history of sudden onset of muscle weakness (cataplexy)