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Methadone can cause changes in brain chemistry that alter sleep regulation. In other words, both the amount and quality of sleep can become shorter and less efficient after methadone abuse. Chronic methadone abuse can often result in insomnia, which can lead to a host of problems.
Try out PMC Labs and tell us what you think. Learn More. 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. The patients receiving MMT had ificantly worse daytime function, were depressed, and had increased daytime sleepiness when compared with the control subjects FOSQ 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 ificantly affect subjective daytime sleepiness and daytime function in these patients. Subjective daytime sleepiness and daytime function in patients on stable methadone maintenance treatment: possible mechanisms.
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J Clin Sleep Med ;4 6 Opioid use has increased rapidly in Western societies, with the major increase being in prescribed opioids, illicit or not. Opioids are commonly used for a of clinical situations, including treatment of acute pain, trauma, cancer, and nonmalignant chronic pain and in methadone maintenance treatment MMT programs. This declaration was to address and improve the situation that clinically ificant chronic pain has not been adequately managed. Recent reports show that there are around 10 million heroin users in the world, with an estimated 2 to 4 million or more in Western Europe and North America alone.
It has been reported that short-term opioid use can cause depressed consciousness or sedation. Although some reports indicate that tolerance develops within a few days on a stable dose of drug and with a return of normal cognitive functioning, other studies suggest that patients continue to experience unpleasant sedative effects and cognitive impairment.
Moreover, given the reported sedative effect of opioids used on a short-term basis and the ificant correlation between CSA and opioid blood concentration, it would be of interest to know whether opioid blood concentration directly or indirectly affects daytime sleepiness and daytime function in patients on stable MMT. The aim of the present study was to investigate the subjective daytime sleepiness using the Epworth Sleepiness Scale [ESS] 17 and daytime function using the Functional Outcomes of Sleep Questionnaire [FOSQ] 18 of patients on stable MMT and to compare the data with those from matched control subjects.
In addition, we have explored the possible mechanisms for the differences found between the patients on MMT and control subjects in particular with respect to sleep architecture, sleep disordered breathing, and opioid blood concentration.
The study was performed in a teaching hospital of The University of Melbourne, Australia. The research protocol was approved by the institutional research and ethics committee.
All subjects gave written informed consent prior to participation. Patients on MMT and control subjects were recruited through advertisements placed in Melbourne pharmacies d to distribute methadone. The research topic was not mentioned in the advertisement.
To be eligible for the study, patients on MMT had to be on methadone for 2 months or longer and had to be on a stable dose of methadone.
Why does methadone make you tired all day?
A screening examination was performed to exclude those subjects with severe cardiac, respiratory, neurologic, or liver disease. Patients who had diagnosed psychotic disorders or pregnant patients were also excluded. Normal control subjects were recruited through advertisements placed on public notice boards with no mention of the research topic. They did not have a current or history of substance abuse and did not have ificant physical or other illnesses, and none were taking medications at the time of the study.
No subject was excluded because of symptoms of sleep disordered breathing. Fifty patients on MMT 25 women, 25 men and 20 normal control subjects 10 women, 10 men completed the study. All subjects completed in-laboratory standard polysomnography Compumedics E series, Victoria, Australia on 2 successive nights with the first night used as acclimatization.
Sleep staging, respiratory events, and arousals were scored in a blinded fashion by DW using standard criteria. The apnea-hypopnea index was calculated as the of apneas and hypopneas divided by total sleep time TST in hours. The central apnea index CAI was defined as the of central apneas per divided by the TST, and obstructive sleep apnea-hypopnea index OSAHI was defined as the total of obstructive apneas plus hypopneas per hour of sleep divided by the TST. Further details are described elsewhere. All subjects had blood taken for toxicology before the second night of polysomnography. All subjects completed the following questionnaires: 1 ESS 17 ; 2 Functional Outcome of Sleep Questionnaire FOSQwhich includes 5 subscales: general productivity, social outcome, activity level, vigilance, and intimate relationship and sexual activity 18 ; 3 the second version of the Beck Depression Inventory BDI-IIwhich was employed to assess How to stay awake on methadone of depression 22 and includes 4 items: agitation, worthlessness, concentration difficulty, and loss of energy; and 4 Modified Mini-Mental Status Examination MMSEwhich was employed to detect cognitive impairment or organic mental disorders.
The modified MMSE makes interpretation possible on an intuitive level and does not require mathematical calculations. Group mean comparisons were assessed using parametric unpaired t-test or nonparametric Mann-Whitney rank sum test where appropriate. Univariate correlations were performed using Pearson correlation coefficient for normally distributed data and Spearman rho for nonnormally distributed data. A multiple linear regression model backward deletion was used to determine the factors associated with the degree of daytime sleepiness and daytime function.
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ESS and square-transformed overall FOSQ scores were the outcome variables, and the predictive variables were the patients' demographic data, BDI, blood toxicology, sleep architecture, and sleep disordered breathing data. Independent variables were examined for colinearity. A p value of less than 0. Detailed sleep architecture, sleep disordered breathing, and blood toxicology data have been published elsewhere.
Sleep architecture and sleep disordered breathing data in patients on MMT and controls subjects are shown in Table 1.
Treatment for methadone addiction
No control subject had CAI greater than 1. Notes : The table was made based on data from Wang et al and is used with permission from the American Thoracic Society.
No control subject had an ESS score greater than All control subjects had a BDI score within the normal range 0—9. Mann-Whitney rank sum tests were tested. The data in Table 3 explore whether CSA and methadone blood concentration play a role in subjective daytime sleepiness and daytime function in the patients on MMT.
Notes : Comparisons were made between patients with and without central sleep apnea and having lower and higher methadone blood concentrations. Except for the BDI, the ificant predictive variables noted in Table 4 were not different between patients on MMT and control subjects. Both the central apnea index and the methadone blood concentration were eliminated early in the backward deletion process. Since we first reported the high prevalence of CSA in patients on stable MMT in11 other studies have confirmed this finding in various patients using opioids on a chronic basis.
In particular, we assessed whether abnormal sleep architecture, CSA severity, and blood methadone concentration play a ificant role in daytime function and subjective daytime sleepiness in patients on stable MMT. Our patients on MMT have a ificantly higher ESS, compared with the control group, but the mean values for both groups are within the range expected in the normal population.
This may be partly due to the wide range of normality for ESS scores.
Similar to reports, the depression level inversely correlated with reduced daytime function. Opioids affect alertness and cognitive function with acute use and during dose escalation. Our data indicate that tolerance to the daytime sedative effect is generally well developed in those patients, although there were a small of individuals who had incomplete tolerance with ificant residual daytime sleepiness and reduced cognitive function.
A lack of relationship between blood methadone concentration and subjective daytime sleepiness and daytime function in our study further supports this conclusion. It has been reported that patients with congestive heart failure who develop Cheyne-Stokes respiration experience excessive daytime sleepiness. Table 1 In addition, the CSA in chronic opioid users may have different underlying mechanisms, as compared with the Cheyne-Stokes respirations in patients to congestive heart failure.
However, because we studied only 50 patients, there is the possibility that a type-II statistical error exists and that, with more subjects, a ificant correlation may indeed exist between the above.
The of multiple regression analysis revealed that obstructive sleep disordered breathing and sleep architecture parameters play an important role in predicting subjective daytime sleepiness and reduced daytime function. This may indirectly explain why patients on MMT have, on average, normal subjective daytime sleepiness and implies that the mildly reduced daytime function in patients on MMT is more related to depression than to sleep disordered breathing or minor changes in sleep architecture parameters. The existence of a relationship between opioid use and psychopathology has been well reported.
It has been reported that mood disorders can independently contribute to impaired daytime performance. As shown in Table 1Stage 1 sleep, Stage 2 sleep, and rapid eye movement sleep times were ificantly different between the patients on stable MMT and control subjects. We therefore believe that these sleep architecture findings are not of clinical ificance in this context. One of the limitations of this study is the use of questionnaires and lack of objective measurements for daytime sleepiness and daytime function.
We would therefore recommend future studies utilizing objective tests such as the Multiple Sleep Latency Test and Maintenance of Wakefulness Test, driving simulator test, and more subtle cognitive function tests. Nevertheless, it should be noted that those objective daytime sleepiness tests also have their limitations. Another limitation is that we could not exclude the potential confounding effects from the concomitant use of drugs such as benzodiazepines, antidepressants, and cannabis, although they are not ificant predictors of daytime sleepiness and daytime function.
Nevertheless, our patients may well be a better representative cohort from community MMT clinics than would be patients taking methadone only.
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In conclusion, we found that the subjective daytime sleepiness in patients on stable MMT is, on average, within the clinical normal range, although the patients' ESS scores were higher, compared with the normal control subjects.
Sleep architecture parameters, the presence of CSA, and the level of blood methadone concentration have no ificant effect on subjective daytime sleepiness and daytime function in these patients on stable MMT. This was not an industry supported study. The authors have indicated no financial conflicts of interest. Professor Harry Teichtahl unfortunately has passed away.