Self-reported Sleep Improvement in Buprenorphine MAT (Medication Assisted Treatment) Population

Research Article

Austin J Drug Abuse and Addict. 2016; 3(1): 1009.

Self-reported Sleep Improvement in Buprenorphine MAT (Medication Assisted Treatment) Population

Zheng WH¹*, Wakim RJ¹, Geary RC¹, Lander LR¹, Wen SJ², Xiao MC² and Sullivan CR¹

¹Department of Behavioral Medicine and Psychiatry, West Virginia University, USA

²Department of Biostatistics, West Virginia University, USA

*Corresponding author: Zheng WH, Department of Behavioral Medicine and Psychiatry, West Virginia University, 930 Chestnut Ridge Road, USA

Received: May 26, 2016; Accepted: July 18, 2016; Published: July 25, 2016


This is a prospective, naturalistic study to evaluate patient’s report on sleep and depression in early recovery while receiving buprenorphine in Medication Assisted Treatment (MAT). 40 Subjects entering into MAT with buprenorphine/ naloxonefor opioid dependence disorder were recruited. No change of concurrent treatment was made. Subjects were administered Sleep Scale from the Medical Outcomes Study (MOS-Sleep), a 5-item Supplemental Sleep Scale (SSS), and the Beck Depression Inventory II (BDI-II). The measures were administered at day 0 (baseline), 30, 60 and 90 days.The result showed that patients reported significant progressive improvements in three MOSSleep subscales: sleep disturbance, sleep indices I and II. The mean scores of SLPD4 (Sleep disturbance) at day 0, 30, 60, 90 were 62.4, 53.2, 53.3, and 48.4 respectively (p=0.0029). Similarly, subscores of SLP6 (Sleep Problem Index I) and SLP 9 (Sleep Problem Index II) were also significantly decreased over time (P=0.038 for SLP6 and p=0.007 for SLP9). BDI-II depression scores improved from “Moderate depression” at baseline to “Mild depression”. The mean BDI score decreased from 24.2 to 17.0 after 90 days of treatment. Findings suggest that subjects reported improvement in both sleep and depression after initiating MAT with buprenorphine/naloxone.

Keywords: Buprenorphine; MAT; Sleep; Depression; MOS-Sleep; BDI-II


MAT: Medication Assisted Treatment; MMT: Methadone Maintenance Therapy; PSQI: Pittsburgh Sleep Quality Index; COAT: Comprehensive Opioid Addiction Treatment; TRD: Treatment Resistant Depression; MOS-Sleep: Sleep Scale from the Medical Outcomes Study; SSS: Supplemental Sleep Scale; BDI-II: Beck’s Depression Inventory II


Opioid dependence disorders have become an epidemic public health concern in the United States. In 2014, 4.3 million Americans age 12 and up, representing 1.6% of the population, reported current non-medical use of prescription pain relievers, while 435,000 people had heroin addiction [1]. Patients with opioid use disorder experience significant sleep distress and depressive mood in various stages: intoxication, withdrawal, chronic use, early recovery and even maintenance therapy [2-6]. This can often be a trigger for relapse and affect the success of treatment. The psycho- and patho- physiologies of sleep impairment in individuals with opioid dependence disorder are multifaceted and complicated. It is always a clinical challenge to determine cause and effect among sleep, depression, and substance use. Chronic substance use disrupts circadian rhythms and thereby impairs the normal sleep-wake cycle [7]. Reports on the direct effect of opioids on sleep quality and efficiency are inconsistent and therefore inconclusive. There has been evidence to support opioid use as a cause of sleep disordered breathing [8], and as a contributor to significant reduction in REM and Stage 3 slow wave sleep as well as to increased risk of central sleep apnea [9,10]. Opioid use has also been associated with increased nocturnal wake times [11]. These effects could be dose related because association was found between prescription opioid status and dose and self-reported sleep impairment [12].

Methadone is a synthetic full opioid agonist that can mitigate opioid withdrawal symptoms. It has been used successfully for more than 40 years in the treatment of opioid dependence [13,14]. Poor sleep function has been reported by patients receiving Methadone Maintenance Therapy (MMT) [15,16]. One study identified that the frequent complaint of sleep disturbance in this population was supported by objective sleep measures such as home polysomnography thereby showing that this population is reliable in evaluating their sleep disturbance [17]. Another study analyzed the correlation between related factors such as duration of opiate exposure, length of time in MMT, current methadone dosage and the severity of sleep disorders. The results showed that more than 70% of patients were poor sleepers and the Pittsburgh Sleep Quality Index (PSQI) and scores correlated significantly with the methadone dosage [18].

Buprenorphine, a partial μ-opioid agonist with limited respiratory toxicity, has been widely used in effective Medication Assisted Treatment (MAT) for opioid dependence disorder. It is associated with many favorable outcomes [19-24]. Like that of methadone, the effect of buprenorphine on sleep disturbance remains unclear. One cross-sectional observational study suggested that buprenorphine/ naloxone might induce significant CSA (Central Sleep Apnea) and hypoxemia [25]. Conversely, one case report indicated successful reversal of CSA with change from methadone to buprenorphinenaloxone [26]. An early study of buprenorphine treatment in heroin dependent men suggested that it could improve sleep disturbance and normalize sleep patterns [27]. Another relevant study showed that slower taper during buprenorphine detoxification correlated with significantly fewer disruptions in sleep compared to the faster tapering experimental groups [28]. Whether buprenorphine has direct effect on breathing and may cause worsening sleep [29] or if it can improve sleep quality by a complicated and unknown mechanism [26-30] is uncertain. Regardless, with increasing use and popularity of buprenorphine in MAT, sleep disturbance and its effect on opioid dependence and early recovery present a unique challenge to the treatment of this population and warrant further research studies.

The relationship between opioid addiction and depression could be very complicated. On one hand, opioid dependence patients often have comorbid depression that may be secondary or primary in the etiology of their addiction problem [31,32]. On the other hand, depression could be a common psychiatric complication in addiction, and one of serious symptoms of opioid use and withdrawal, constituting a firm reinforcement of continued addiction [33-35]. Moreover, the loss of self-control, shame and guilty, helplessness, hopelessness, subsequent disruption of job performance and social ties, even criminal behavior can all cause addicted people to suffer from worsening mood deterioration and dysphoria. Interestingly, buprenorphine as a potent kappa antagonist has been shown to have antidepressant activity [36,37]. A recent open label clinical trial demonstrated that buprenorphine combined with a mu opioid antagonist significantly reduced depressive symptoms in individuals with Treatment Resistant Depression (TRD) [38]. This indicates that modulation of the opiate system has something to do with depression and using buprenorphine like product may be a novel treatment approach for TRD. Sleep problem, as one of the diagnostic symptoms of depression, is also a risk factor, consequence, and complication of both depression and drug addiction [39,40]. Often it serves as a prognostic indicator of long-term depression course and treatment response. Although insomnia usually improves as depression is treated, it may persist in addiction patients, indicating a separate etiology and need for further intervention. The above all add complexity to the study of sleep in MAT population but also suggest greater need for thorough mood assessment at MAT treatment entry and continuous close monitoring throughout the treatment course.

The primary outcome investigated in the present study was the effect of buprenorphine used in MAT on sleep. We hypothesized that patients would report poor sleep at entry into treatment and show improvement in sleep over time. The secondary outcome measured was the effect of buprenorphine used in MAT in depression. We hypothesized subjects would report improvement in depression as assessed by the Beck Depression Inventory II (BDI-II).


Study setting and participants

This study was completed at West Virginia University Department of Behavioral Medicine and Psychiatry Chestnut Ridge Center, one of the largest mental health service centers in West Virginia. The center provides outpatient opioid addiction treatment through interdisciplinary team approach named the Comprehensive Opioid Addiction Treatment (COAT) program. It includes group based medication management followed by substance abuse focused group therapy. Patients are also required to participate in 12-step peer support meetings. All participants were diagnosed with Opioid Dependence (DSM IV) and at the time of the study were entering into COAT MAT using buprenorphine/naloxone. Per prescribing information [41], the inclusion of naloxone in the sublingual formulation is to help deter the possible diversion of buprenorphine to misuse by the parenteral route. Although blood concentration might be measureable, when administered by the sublingual route, naloxone was reported to have no clinically significant effect. Therefore we only refer to the active ingredient buprenorphine for this research purpose. Informed consent was obtained prior to participation. Subjects received no monetary compensation. The only exclusion criterion was active pregnancy. No change in concurrent treatment was made in hopes that this would allow for a more representative sample of outpatients in “real world” practice. Per clinic policy, we maintain a list of medications (including most of the controlled substances such as Benzodiazepines, Z-drugs, stimulants, etc.) that were disallowed for the purpose of buprenorphine maintenance treatment. To ensure compliance and avoid drug diversion, patients are subject to random pill counts and random urine drug screens. Buprenorphine and its metabolite nor-buprenorphine must be present in the urine screen in order for new prescription to be written. The study was consistent with protection of patient rights per Health Insurance Portability and Accountability Act and was approved by the West Virginia University institutional review boards.


Sleep scale from the Medical Outcomes Study (MOSSleep)

The MOS-Sleep is a 12-item self-report questionnaire that measures six dimensions of sleep: “sleep disturbance,” “snoring,” “sleep awakening short of breath or with headache,” “sleep adequacy,” “somnolence,” and “quantity of sleep/optimal sleep” [42,43]. Based on a comprehensive conceptual model that covers both physical and mental health, it was originally designed for patients with chronic illness but was also validated in general population as an effective approach to the sleep assessment [42,44-47]. The item and subscale contents of the MOS-Sleep are presented in (Table 1) [43].