Role of Enhancing Serotonin Receptors Activity for Sleep Apnea Treatment in Patients With SCI

Randomized placebo controlled cross-over study. Each subject will be studied on three separate occasions: (1) Buspirone vs. Trazodone vs. placebo for 2 weeks; the patients will be blinded to whether they are taking trazodone or placebo; buspirone cannot be blinded because it is dosed twice a day and is up titrated during the two weeks of administration. The initial dose of Buspirone is 15 mg daily (7.5 mg bid.). To achieve an optimal therapeutic response, at intervals of 2 to 3 days the dosage may be increased 5 mg per day until a maximum dose 30mg/day is reached. After the two week treatment a sleep study will be repeated. Trazodone will be given at 100 mg dose before bed-time. (2) Cross over medication for two weeks will be followed by a second sleep study followed by two weeks washout. (3) Cross over medication for two weeks will be followed by another sleep study. To assess the clinical effect of the drug on breathing during sleep a qualitative polysomnography will be performed for 2 hours the same night after taking the drug/placebo. This will allow the determination of ventilatory changes and the determination of the number of respiratory events (apnea/hypopnea index).

Inclusion criteria

• Adults with SCI (>6months after spinal cord injury) at the T6 level/above

Exclusion criteria

• Pregnant and lactating females
• Heart failure, vascular disease, or stroke
• Advanced chronic obstructive pulmonary disease (COPD), liver disease, and chronic kidney disease
• BMI >38 kg/m2
• Mechanical ventilation dependence
• The following medications are not allowed (potential interaction with buspirone or inhibition of the CYP3A4 system):

• cimetidine
• ketoconazole
• ritonavir
• itraconazole
• erythromycin
• diltiazem
• verapamil
• Monoamine oxidase (MAO) inhibitors [such as Marplan, Nardil, Parmate, Emsam]
• Other prohibited concomitant medications include haloperidol, trazodone, or triazolam