Max Hirshkowitz1, Jed Black. 1. Michael E. DeBakey Veterans Affairs Medical Center - Sleep Diagnostic Clinic, Houston, Texas, USA. maxh@bcm.edu
Abstract
OBJECTIVE: To evaluate the long-term effect on wakefulness, functional status and quality of life and tolerability of adjunctive modafinil in continuous positive airway pressure (CPAP)-treated patients with residual excessive sleepiness (ES) associated with obstructive sleep apnoea/hypopnoea syndrome (OSA/HS). STUDY DESIGN: 12-month, open-label extension of a 12-week, randomised, double-blind, placebo-controlled study. SETTING:Thirty-seven centres in the US and four in the UK. PATIENTS: Two hundred and sixty-six patients experiencing ES associated with OSA/HS who completed at least 8 weeks of the 12-week double-blind study, and who received adequate education and intervention efforts to encourage use of nasal CPAP (nCPAP). INTERVENTION: Patients receiving nCPAP therapy were administered modafinil 200 mg/day during week 1, 300 mg/day during week 2, and then 200, 300 or 400 mg/day, based on the investigator's assessment of efficacy and tolerability, for the remainder of the study. MAIN OUTCOME MEASURES: Assessments included the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ) and Short Form-36 Health Survey (SF-36). RESULTS:One hundred and seventy five patients (66%) completed the study. Modafinil maintained a significant effect on wakefulness, as shown by improvement in the ESS total score at months 3, 6, 9 and 12 compared with baseline (all p < 0.0001). Modafinil also improved functional status (FOSQ total score) and general health (SF-36 mental and physical component scores) at months 6 and 12 compared with baseline (all p < 0.05). Modafinil was well tolerated. The most common adverse events reported were infection (11.3%), headache (9.4%) and nervousness (9.0%). Serious adverse events were reported in 13 patients, with two of these events (mild bradycardia and severe syncope, both in the same patient) considered to be possibly related to modafinil. There were few clinically meaningful changes in clinical laboratory data, vital signs, physical examination findings or ECG results. Important changes included significant increase in blood pressure in six patients, five of whom had a history of hypertension. CONCLUSIONS:Adjunctive modafinil maintained effects on wakefulness and functional outcomes, and improved quality of life in patients with OSA/HS experiencing residual ES over a 12-month period. Modafinil was well tolerated during long-term therapy.
RCT Entities:
OBJECTIVE: To evaluate the long-term effect on wakefulness, functional status and quality of life and tolerability of adjunctive modafinil in continuous positive airway pressure (CPAP)-treated patients with residual excessive sleepiness (ES) associated with obstructive sleep apnoea/hypopnoea syndrome (OSA/HS). STUDY DESIGN: 12-month, open-label extension of a 12-week, randomised, double-blind, placebo-controlled study. SETTING: Thirty-seven centres in the US and four in the UK. PATIENTS: Two hundred and sixty-six patients experiencing ES associated with OSA/HS who completed at least 8 weeks of the 12-week double-blind study, and who received adequate education and intervention efforts to encourage use of nasal CPAP (nCPAP). INTERVENTION: Patients receiving nCPAP therapy were administered modafinil 200 mg/day during week 1, 300 mg/day during week 2, and then 200, 300 or 400 mg/day, based on the investigator's assessment of efficacy and tolerability, for the remainder of the study. MAIN OUTCOME MEASURES: Assessments included the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ) and Short Form-36 Health Survey (SF-36). RESULTS: One hundred and seventy five patients (66%) completed the study. Modafinil maintained a significant effect on wakefulness, as shown by improvement in the ESS total score at months 3, 6, 9 and 12 compared with baseline (all p < 0.0001). Modafinil also improved functional status (FOSQ total score) and general health (SF-36 mental and physical component scores) at months 6 and 12 compared with baseline (all p < 0.05). Modafinil was well tolerated. The most common adverse events reported were infection (11.3%), headache (9.4%) and nervousness (9.0%). Serious adverse events were reported in 13 patients, with two of these events (mild bradycardia and severe syncope, both in the same patient) considered to be possibly related to modafinil. There were few clinically meaningful changes in clinical laboratory data, vital signs, physical examination findings or ECG results. Important changes included significant increase in blood pressure in six patients, five of whom had a history of hypertension. CONCLUSIONS: Adjunctive modafinil maintained effects on wakefulness and functional outcomes, and improved quality of life in patients with OSA/HS experiencing residual ES over a 12-month period. Modafinil was well tolerated during long-term therapy.
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