Documented poor sleep among methadone-maintained patients is associated with chronic pain and benzodiazepine abuse, but not with methadone dose
Introduction
The methadone-maintained dose that effectively eliminates withdrawal symptoms and craving among opiate addicts is highly varied between patients, and is related to several factors (i.e., individual metabolism, addiction level and duration, polymorphism of opioid receptors and/or of cytochrome P-450 in the liver etc. For more details see Adelson et al., 2007). Therapeutic dose is adjusted for each patient individually, with no ‘up limit’ dose as long as it doesn't extend beyond the ‘therapeutic window’ for methadone serum level.
Perceived poor sleep quality was reported to be highly prevalent among methadone maintenance treatment (MMT) patients (Stein et al., 2004, Peles et al., 2006). Stein et al. (2004) reported that 84% of MMT patients have sleep disturbances, and a cross-sectional study from our clinic reported a prevalence of 75.2% (Peles et al., 2006). However, both of these studies measured perceived (subjective) sleep quality and not objectively measured sleep patterns, with both using the self-report questionnaire Pittsburgh Sleep Quality Index (PSQI).
Perceived sleep is based on self-report (PSQI) questionnaire that covers subjectively, the sleep quality, latency, duration and habitual sleep efficiency. All these parameter are objectively measured during the polysomnography (PSG) registration in the sleep laboratory, in addition to other parameters, such as sleep architecture, the proportion of each stage (i.e.: the non rapid eye movement (NREM) light sleep stages 1–2, the restorative deep sleep NREM stages 3–4, and the Rapid Eye Movement (REM) stage).
A high prevalence (37–61%) of chronic pain was also reported among former heroin patients currently in MMT (Jamison et al., 2000, Rosenblum et al., 2003, Peles et al., 2005). The chronic pain patients were characterized as suffering from any medical illness and abusing benzodiazepines (BDZ), and in two of the three reports (Jamison et al., 2000, Peles et al., 2005) these patients were found to be treated with higher methadone doses than the non-chronic pain patients for their addiction, unrelated to the presence and extent of pain.
In the general population, several studies have shown that at least half of the patients with diverse types of chronic pain complaints have significant sleep disturbances, and some investigations reported a prevalence of sleep disturbances as high as 67–88% in chronic pain patients (Smith et al., 2000, Morin et al., 1998). There are consistent links between self-reported sleep disruption and pain severity (Stone et al., 1997, Wilson et al., 2002). More than three decades ago it was hypothesized (Moldofsky and Scarisbrick, 1976) that sleep disturbances and chronic pain can be considered as parts of a reciprocal vicious cycle, with pain contributing to disturbed sleep and disturbed sleep contributing to enhanced pain sensitivity and negative mood states.
The relation between pain and objective sleep quality among MMT patients has not been studied yet. We hypothesize that chronic pain as well as BDZ abuse may be at least partially responsible for sleep disturbances in MMT patients. Since in our previous study which evaluated perceived sleep (Peles et al., 2006) we found linear correlation between methadone dose and severity of subjective sleep disturbances (PSQI score), we decide in the current study to especially recruit stable MMT patients on either high (> 150 mg/d) or low (< 80 mg/d) daily methadone doses in order to study, in addition to their perceived sleep, objective parameters of their sleep, by an overnight polysomnography (PSG) as well. In particular, we focused on chronic pain, BDZ abuse and other risk factors.
Thus, by coupling subjective complaints with objective measurements and other data from the patients' clinical data, a rather accurate explanation for the patients' sleep problems may be formulated.
Section snippets
Study population
Forty four patients from the Adelson Clinic for Drug Abuse Treatment and Research in Tel-Aviv participated in the study. The study was approved by the Helsinki Committee (IRB) of the Tel-Aviv Sourasky Medical Center (TASMC) (216-7/05). All study patients met criteria similar to those of the U.S. Federal Regulations for entering methadone treatment (i.e., DSM-IV-TR criteria of dependence on multi-self-administrations of heroin for 1 year or more)(APA, 2000). Between October 2006 and September
Sleep indices and methadone dose (Table 1)
A total of 44 patients: 25 with high- and 19 with low methadone doses participated. The high methadone patients characterized as older aged patients (49.2 ± 9.0 vs. 41.8 ± 8.7) with longer duration of opiate abuse before admission MMT (21.9 ± 8.8 vs. 14.2 ± 9.2). Groups did not differ with respect to duration in MMT and gender distribution. The high and low methadone dose did not differ in proportion of chronic pain, BDZ abuse, and other risk factors that are known as being associated with poor sleep
Discussion
Our data suggest that poor sleep among MMT patients does not relate to their methadone dose but rather to their additional problems, namely chronic pain and BDZ abuse. Sleep disturbances are one of the main complaints brought to the GP all over the world (second only to pain complaints), and are known to afflict many healthy individuals which conduct normal and productive day to day life. Furthermore, it is an extremely frequent complaint of drug abusers, and its resolution may be one of the
Limitations
In the current study due to the small sample size we've compared only chronic pain with non-chronic pain patients. However, future studies with a larger sample size would enable to evaluate a possible dose-response relation between pain severity and/or duration and parameters of sleep quality and disturbance, as well as the possible correlation with various pain sites distribution over the head/neck, limbs or trunk (Defrin et al., 2008). With respect to BDZ abuse, in a larger sample size we
Role of the funding source
This study was supported by a grant from “The Israel Anti Drug Authority” and support of “The Adelson Family Foundation.”
Contributors
All authors contributed to all part of the study design and to the preparation of the manuscript and have approved the final paper. Peles E undertook the statistical analysis.
Conflict of interest
All authors declare that there are no conflicts of interest.
Acknowledgment
Many thanks to Esther Eshkol for editorial assistance, to Prof. Peretz Lavie for insightful counseling regarding the study design, to Suheir Suraiya for the PSG data assessment, and to Anat Sason for all assistance.
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2020, Sleep MedicineCitation Excerpt :PSQI was not correlated with duration in MMT, gender, age, abuse of opiates, cannabis or cocaine. Peles et al. [70], studied 44 former heroin dependent patients maintained on “low” (n = 19, 80 mg/d) or “high” (n = 25, 150 mg/d) methadone doses. The patients underwent one-night PSG.
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Drs. Peles and Schreiber contributed equally to the study and the manuscript preparation.