Subjective daytime sleepiness and daytime function in patients on stable methadone maintenance treatment: possible mechanisms.

INTRODUCTION: Subjects using opioids on a chronic basis have been reported to have a high prevalence of abnormal sleep architecture and central sleep apnea (CSA). The severity of CSA is, in part, related to blood opioid concentration. The aim of this study was to investigate subjective daytime sleepiness and daytime function in patients who are on stable methadone maintenance treatment (MMT) and to assess the possible mechanisms involving abnormal sleep architecture, CSA severity, and blood methadone concentration. METHODS: Fifty patients on MMT and 20 normal control subjects matched for age and body mass index were tested using polysomnography, blood toxicology, Epworth Sleepiness Scale (ESS), Functional Outcome of Sleep Questionnaire (FOSQ), and Beck Depression Inventory (BDI). RESULTS: The patients receiving MMT had significantly worse daytime function, were depressed, and had increased daytime sleepiness when compared with the control subjects (FOSQ 15.47 +/- 3.19 vs 19.4 +/- 0.47, BDI 14.64 +/- 10.58 vs 2.05 +/- 2.46, ESS 7.1 +/- 5 vs 2.05 +/- 1.76; all p values < 0.001). Nevertheless, daytime sleepiness in the patients receiving MMT was, on average, within the normal range (ESS < or = 10). Multiple regression analysis demonstrated that the severity of CSA, blood methadone concentration, and abnormalities in sleep architecture were not significant in predicting the variance of ESS or FOSQ (all p values > 0.05) in these patients receiving MMT. The BDI was the best predictive variable for FOSQ, explaining 16% of the variance (p = 0.004). CONCLUSIONS: Patients on stable MMT have, in general, normal subjective daytime sleepiness but impaired daytime function that partially relates to depression. The changes in sleep architecture, presence of CSA, and blood methadone concentrations do not significantly affect subjective daytime sleepiness and daytime function in these patients.

Central sleep apnea in stable methadone maintenance treatment patients.

STUDY OBJECTIVES: Methadone, a long-acting mu-opioid agonist, is an effective treatment for heroin addiction. Our previous data show that 6 of 10 methadone maintenance treatment (MMT) patients had central sleep apnea (CSA). This study aims to confirm these results and to investigate the pathogenesis of the CSA. METHODS: Twenty-five male and 25 female MMT patients and 20 age-, sex-, and body mass index (BMI)-matched normal subjects were tested with polysomnography, blood toxicology, and ventilatory responses to hypoxia and hypercapnia. Resting cardiorespiratory tests were performed in the MMT group RESULTS: MMT patients and normal subjects were 35 +/- 9 years old (mean +/- SD), and BMI values were 27 +/- 6 kg/m2 and 27 +/- 5 kg/m2, respectively. Thirty percent of MMT patients had a central apnea index (CAI) > 5, and 20% had a CAI > 10. All normal subjects had a CAI < 1, and no difference was found in obstructive apnea-hypopnea index between the two groups. Methadone blood concentration was the only significant variable (t = 2.33, p = 0.025) associated with CAI and explains 12% of the variance. Awake Pa(CO2), antidepressant use, reduced ventilatory response to hypercapnia, and widened awake alveolar-arterial oxygen pressure gradient together explain a further 17% of the CAI variance. CONCLUSIONS: Thirty percent of stable MMT patients have CSA, a minority of which can be explained by blood methadone concentration. Other physiologic variables may also play a role in the pathogenesis of CSA in MMT patients, and further research is indicated in this area.

Cardiorespiratory function in stable methadone maintenance treatment (MMT) patients.

Patients in methadone maintenance programmes (MMT) often smoke tobacco and cannabis and many have ongoing illicit drug use. There is therefore potential for these patients to have abnormal cardiorespiratory function; however, few studies address this in stable MMT patients. We assessed resting cardiorespiratory function on 50 stable MMT patients (25 males, 25 females). Forty-six MMT patients were current tobacco smokers, 19 were current cannabis users and none were currently using opioids other than prescribed methadone. We defined abnormalities of respiratory function as those results outside the 95% confidence interval of reference values for normal subjects adjusted for age, weight, height and sex. Thirty-one (62%) MMT patients had reduced carbon monoxide transfer factor (D(L)CO); 17 (34%) had elevated single breath alveolar volume (V(A)) and 43 (86%) had a reduced D(L)CO/V(A) ratio. Six patients (12%) had reduced FEV1; one (2%) had reduced FVC; and nine (18%) had an obstructive ventilatory defect. Ten (20%) patients had PaCO2 higher than 45 mmHg and 14 (28%) had alveolar to arterial oxygen gradient (A-aPO2) higher than 15 mmHg. CXR, Echocardiography and ECG showed no significant abnormalities. We conclude that stable MMT patients have abnormalities of resting respiratory function which may be due to ongoing tobacco cigarette and current or past cannabis smoking.