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1.
Front Psychiatry ; 14: 1103739, 2023.
Article in English | MEDLINE | ID: mdl-36741122

ABSTRACT

Background: Benzodiazepine (BZD) misuse is a significant public health problem, particularly in conjunction with opioid use, due to increased risks of overdose and death. One putative mechanism underlying BZD misuse is affective dysregulation, via exaggerated negative affect (e.g., anxiety, depression, stress-reactivity) and/or impaired positive affect (anhedonia). Similar to other misused substances, BZD consumption is sensitive to price and individual differences. Although purchase tasks and demand curve analysis can shed light on determinants of substance use, few studies have examined BZD demand, nor factors related to demand. Methods: This ongoing study is examining simulated economic demand for alprazolam (among BZD lifetime misusers based on self-report and DSM-5 diagnosis; n = 23 total; 14 male, 9 female) and each participant's preferred-opioid/route using hypothetical purchase tasks among patients with opioid use disorder (n = 59 total; 38 male, 21 female) who are not clinically stable, i.e., defined as being early in treatment or in treatment longer but with recent substance use. Aims are to determine whether: (1) BZD misusers differ from never-misusers on preferred-opioid economic demand, affective dysregulation (using questionnaire and performance measures), insomnia/behavioral alertness, psychiatric diagnoses or medications, or urinalysis results; and (2) alprazolam demand among BZD misusers is related to affective dysregulation or other measures. Results: Lifetime BZD misuse is significantly (p < 0.05) related to current major depressive disorder diagnosis, opioid-negative and methadone-negative urinalysis, higher trait anxiety, greater self-reported affective dysregulation, and younger age, but not preferred-opioid demand or insomnia/behavioral alertness. Alprazolam and opioid demand are each significantly positively related to higher anhedonia and, to a lesser extent, depression symptoms but no other measures of negative-affective dysregulation, psychiatric conditions or medications (including opioid agonist therapy or inpatient/outpatient treatment modality), or sleep-related problems. Conclusion: Anhedonia (positive-affective deficit) robustly predicted increased BZD and opioid demand; these factors could modulate treatment response. Routine assessment and effective treatment of anhedonia in populations with concurrent opioid and sedative use disorder may improve treatment outcomes. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03696017, identifier NCT03696017.

2.
Pharmacol Biochem Behav ; 213: 173330, 2022 02.
Article in English | MEDLINE | ID: mdl-34995638

ABSTRACT

The objective of this editorial is to summarize the findings published in the special issue on "Sleep and Drug Abuse". The manuscripts in this issue include review articles as well as original investigations, and cover topics ranging from pre-clinical investigation to epidemiological-based clinical studies. Together, these papers provide evidence that sleep and drug abuse share a bidirectional relationship, with sleep playing a prominent role in substance use disorders. The knowledge included here can inform treatment development and future research endeavors, clearly pointing to the need for attention that focuses on sleep quality in the treatment of substance use disorders.


Subject(s)
Sleep , Substance-Related Disorders/epidemiology , Humans , Prevalence , Review Literature as Topic , Sleep Quality , Sleep Wake Disorders/epidemiology , Substance-Related Disorders/therapy
3.
Transl Res ; 234: 58-73, 2021 08.
Article in English | MEDLINE | ID: mdl-33711513

ABSTRACT

Due to the ongoing opioid epidemic, innovative scientific perspectives and approaches are urgently needed to reduce the unprecedented personal and societal burdens of nonmedical and recreational opioid use. One promising opportunity is to focus on the relationship between sleep deficiency and opioid use. In this review, we examine empirical evidence: (1) at the interface of sleep deficiency and opioid use, including hypothesized bidirectional associations between sleep efficiency and opioid abstinence; (2) as to whether normalization of sleep deficiency might directly or indirectly improve opioid abstinence (and vice versa); and (3) regarding mechanisms that could link improvements in sleep to opioid abstinence. Based on available data, we identify candidate sleep-restorative therapeutic approaches that should be examined in rigorous clinical trials.


Subject(s)
Opioid-Related Disorders/complications , Sleep Deprivation/complications , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Behavior Therapy/methods , Biogenic Monoamines/therapeutic use , Endocannabinoids/therapeutic use , Humans , Opioid Epidemic , Opioid-Related Disorders/physiopathology , Opioid-Related Disorders/therapy , Orexin Receptor Antagonists/therapeutic use , Physical Therapy Modalities , Receptors, Melatonin/agonists , Sleep Deprivation/physiopathology , Sleep Deprivation/therapy , Translational Research, Biomedical
4.
Pharmacol Biochem Behav ; 203: 173153, 2021 04.
Article in English | MEDLINE | ID: mdl-33582097

ABSTRACT

The majority of the literature describing the relation of sleep/alertness disturbance and substance use disorders (SUD) has focused on the disruptive effects of substances with abuse liability on sleep and alertness. Rarely have studies or literature reviews assessed or discussed how sleep/alertness disturbance affects substance use. This paper focuses on the sleep/alertness disturbance side of the relation. We argue that the relation is bi-directional and review evidence showing that sleep/alertness disturbance affects all phases of the addiction cycle, including the initiation, maintenance and relapse of SUD. We review a variety of substances across all phases of the addiction cycle and conclude sleep/alertness disturbance is a critical factor in both understanding and treating SUD.


Subject(s)
Sleep Wake Disorders/complications , Sleep, REM/drug effects , Sleep, Slow-Wave/drug effects , Substance-Related Disorders/complications , Adolescent , Adult , Circadian Clocks/drug effects , Circadian Rhythm/drug effects , Female , Humans , Male , Recurrence , Sleep Wake Disorders/metabolism , Substance-Related Disorders/metabolism , Young Adult
5.
Neuropsychopharmacol Rep ; 40(3): 211-223, 2020 09.
Article in English | MEDLINE | ID: mdl-32543111

ABSTRACT

Alcohol use disorder (AUD) is characterized by dysfunction in motivational, mood-stress regulation, and sleep systems that interact in complex ways to heighten the risk of relapse during abstinence. Emerging data suggest that excessive and chronic alcohol use disrupts sleep homeostasis and, in abstinence, subjects with AUD are known to experience insomnia that may persist for weeks to years, which we propose to refer to as insomnia associated with alcohol cessation (IAAC). The purpose of this review is to provide an update of pharmacological approaches to therapy including compounds in development, to raise awareness of the prevalence of and unmet need in IAAC and highlight differences in treatment consideration for IAAC as compared to insomnia disorder. We performed a search of select electronic databases to identify studies of pharmacological agents used to treat sleep disturbances in abstinent or treatment-seeking patients with alcohol use disorder. The search, conducted in June 2019 and updated in December 2019, yielded 1,188 abstracts after duplicates were removed, of which 36 full-text articles were assessed for eligibility. Eighteen studies were included, 15 randomized controlled trials and three open-label studies. Several classes of medications including antidepressants, anticonvulsants, and antipsychotics have been evaluated for their effectiveness in treating sleep disturbances in abstinent or treatment-seeking patients with AUD. None of these medications are approved by the FDA for the treatment of IAAC, and the currently available evidence for these agents is limited. Randomized, controlled clinical trials are warranted to evaluate the efficacy and safety of medications in the treatment of IAAC.


Subject(s)
Alcohol Abstinence/trends , Alcoholism/complications , Alcoholism/drug therapy , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/etiology , Alcoholism/physiopathology , Anticonvulsants/therapeutic use , Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Humans , Melatonin/therapeutic use , Randomized Controlled Trials as Topic/methods , Sleep Initiation and Maintenance Disorders/physiopathology
6.
J Clin Sleep Med ; 16(3): 415-421, 2020 03 15.
Article in English | MEDLINE | ID: mdl-31992394

ABSTRACT

STUDY OBJECTIVES: The chronic pain disorder, fibromyalgia, is associated with sleep disturbance, typically sleep maintenance. No studies have evaluated the effect of sleep medication on pain sensitivity in this population. Suvorexant, an orexin antagonist approved for treatment of insomnia, was evaluated for effects on both sleep and the pain of fibromyalgia. METHODS: Women age 21 to 65 years with fibromyalgia and comorbid insomnia (n = 10) were treated, double-blind, for 9 nights each with suvorexant, 20 mg and placebo in counterbalanced order. All were in good psychiatric and stable physical health and met American College of Rheumatology 2010 criteria for fibromyalgia and Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition criteria for insomnia. Screening 8-hour polysomnography (PSG) was used to rule out other sleep disorders. On nights 8 and 9 of each treatment 8-hour PSG were collected and on days 1 and 8 pain sensitivity was assessed at 1100 and 1500 hours by measuring finger withdrawal latency (FWL) to a radiant heat stimulus at 5 randomly presented intensity levels. RESULTS: Suvorexant versus placebo increased total sleep time (7.2 versus 6.7 hours, P < .05) and reduced wake after sleep onset (37 versus 67 minutes, P < .04) with no night effects or interaction. Latency to persistent sleep and sleep stage measures were not altered. FWL on both am and pm tests varied as a function of intensity (P < .001). Average FWL (over 5 intensities and both days) was increased relative to placebo on both the am (13.9 versus 13.1 seconds) and pm tests (15.8 versus 14.1 seconds, P < .03) following suvorexant the previous night. CONCLUSIONS: Suvorexant 20 mg in patients with fibromyalgia, improved sleep time and reduced next-day pain sensitivity on assessments of FWL to a radiant heat stimulus. CLINICAL TRIAL REGISTRY: Registry: ClinicalTrials.gov; Name: A double-blind cross-over, study to compare the hypnotic, daytime sleepiness/fatigue, and pain effects of nighttime administration of suvorexant 20 mg versus placebo in patients with fibromyalgia and comorbid insomnia; Identifier: NCT02684136; URL: https://clinicaltrials.gov/ct2/show/NCT02684136.


Subject(s)
Fibromyalgia , Sleep Initiation and Maintenance Disorders , Adult , Aged , Azepines/therapeutic use , Cross-Over Studies , Double-Blind Method , Female , Fibromyalgia/complications , Fibromyalgia/drug therapy , Fibromyalgia/epidemiology , Humans , Middle Aged , Pain , Sleep , Sleep Initiation and Maintenance Disorders/complications , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/epidemiology , Treatment Outcome , Triazoles , Young Adult
7.
J Clin Sleep Med ; 15(12): 1863-1865, 2019 12 15.
Article in English | MEDLINE | ID: mdl-31855173

ABSTRACT

None: The prevalence of shift work in the United States is nearly 20%, but recognition of shift work disorder (SWD) among shift workers is still a challenge. The health care sector is no exception. While a substantial portion of shift workers are physicians and nurses, expertise in identifying SWD is lacking. Shift work adjustment occurs spontaneously in some individuals, but for others, it poses difficulties, including both sleep disturbance and insufficient sleep, leading to chronic excessive sleepiness and other long-term morbidities. Treatment is multifaceted and often requires pharmacologic therapy to address acute sleep-wake symptoms, as well as circadian interventions to realign intrinsic biological rhythms to the externally imposed shift-work schedule. The complexity and myriad obstacles of treating maladjustment to shift work after its manifestation, including determination of circadian phase, risk-benefit considerations in pharmacologic treatment, and behavioral/health risks associated with delaying intervention, suggest that prevention of SWD should be a priority. This article presents the personal experience of one author (Amit Gupta), identifies some of the issues faced by shift workers, especially medical trainees, and suggests a preventive approach to this complex problem that should be considered for future research and practical implementation in the clinic.


Subject(s)
Shift Work Schedule/adverse effects , Sleep Disorders, Circadian Rhythm/therapy , Humans , Sleep Disorders, Circadian Rhythm/etiology , Work Schedule Tolerance
8.
J Clin Sleep Med ; 15(7): 999-1010, 2019 07 15.
Article in English | MEDLINE | ID: mdl-31383238

ABSTRACT

STUDY OBJECTIVES: Insomnia is a chief complaint among postmenopausal women, and insomnia impairs daytime functioning and reduces quality of life. Recent evidence supports the efficacy of cognitive behavioral therapy for insomnia (CBTI) for menopausal insomnia, but it remains unclear whether treating insomnia improves daytime function in this population. This study evaluated whether CBTI improves daytime fatigue, energy, self-reported sleepiness, work productivity, and quality of life in postmenopausal women with insomnia, and whether sleep restriction therapy (SRT)-a single component of CBTI-is equally efficacious. METHODS: Single-site, randomized control trial. One hundred fifty postmenopausal women (56.44 ± 5.64 years) with perimenopausal or postmenopausal onset or exacerbation of chronic insomnia were randomized to 3 treatment conditions: sleep hygiene education control (SHE), SRT, and CBTI. Blinded assessments were performed at pretreatment, posttreatment, and 6-month follow-up. RESULTS: CBTI and SRT produced moderate-to-large improvements in fatigue, energy, sleepiness, and work function at posttreatment and 6 months later. The CBTI group reported better quality of life as indicated by substantial improvements in emotional wellbeing and resiliency to physical and emotional problems, whereas the SRT and SHE groups only showed improvements in resiliency to physical problems. Pain complaints decreased as sleep improved but were not associated with specific treatment conditions. Similarly, insomnia remitters reported fewer daytime and nighttime hot flashes, although reductions were not associated with any specific treatment. CONCLUSIONS: CBTI and SRT are efficacious options for postmenopausal women with chronic insomnia. Both interventions improve daytime function, quality of life, and work performance, although CBTI produces superior results including the added benefit of improved emotional health. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Behavioral Treatment of Menopausal Insomnia; Sleep and Daytime Outcomes; Identifier: NCT01933295; URL: https://clinicaltrials.gov/ct2/show/record/NCT01933295.


Subject(s)
Behavior Therapy/methods , Patient Education as Topic/methods , Quality of Life , Sleep Hygiene , Sleep Initiation and Maintenance Disorders/therapy , Work Performance/statistics & numerical data , Cognitive Behavioral Therapy/methods , Female , Humans , Middle Aged , Postmenopause , Surveys and Questionnaires , Treatment Outcome
9.
Sleep Med ; 61: 52-56, 2019 09.
Article in English | MEDLINE | ID: mdl-31255482

ABSTRACT

OBJECTIVES: To determine whether cortisol levels, both diurnal and pre-sleep, would vary as a function of MSLT and would be reduced by nightly placebo versus zolpidem 10 mg. METHODS: DSM-IVR diagnosed subjects with insomnia (N = 95), aged 32-70 yrs, having no other sleep disorder, unstable medical or psychiatric diseases or drug dependency served. On a screening MSLT 27 had MSLTs <10 min (Lo) and 42 > 15 min (Hi). Participants took 10 mg zolpidem or placebo, double-blind, nightly for 12 months. In months one and 12 urine was collected over 24 h in 8 hr-aliquots and assayed for cortisol (Ward Laboratories, Ann Arbor, MI). Saliva samples were collected 35 min before bedtime and the 30 min drug administration in month one and eight, and analyzed for cortisol levels (Salimetrics, State College, PA). RESULTS: Pre-sleep salivary cortisol was higher in insomniacs than controls, but did not differ as a function of MSLT. Nightly zolpidem reduced pre-sleep cortisol relative to placebo on month one and eight, with no month effects or interaction. Diurnal (0700-1500 h) urinary cortisol was higher overall in the Hi vs Lo MSLT subjects with insomnia, was stable across months, and was not reduced with zolpidem. CONCLUSIONS: Hyperarousal among subjects with insomnia as operationalized by MSLT is associated with higher diurnal urinary cortisol than those without hyperarousal, but not differential pre-sleep salivary cortisol. Zolpidem relative to placebo reduced pre-sleep salivary cortisol in all subjects, but not diurnal urinary cortisol. CLINICAL TRIAL: Safety and Efficacy of Chronic Hypnotic Use: http://www.clinicaltrials.gov NCT01006525.


Subject(s)
Hydrocortisone/metabolism , Sleep Aids, Pharmaceutical/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/metabolism , Zolpidem/therapeutic use , Adult , Aged , Arousal/drug effects , Double-Blind Method , Female , Humans , Male , Middle Aged , Young Adult
10.
J Sleep Res ; 28(4): e12854, 2019 08.
Article in English | MEDLINE | ID: mdl-30941838

ABSTRACT

Actigraphy is increasingly used in practice and research studies because of its relative low cost and decreased subject burden. How multiple nights of at-home actigraphy compare to one independent night of in-laboratory polysomnography (PSG) has not been examined in people with insomnia. Using event markers (MARK) to set time in bed (TIB) compared to automatic program analysis (AUTO) has not been systematically evaluated. Subjects (n = 30) meeting DSM-5 criteria for insomnia and in-laboratory PSG sleep efficiency (SE) of <85% were studied. Subjects were free of psychiatric, sleep or circadian disorders, other chronic conditions and medications that effect sleep. Subjects had an in-laboratory PSG, then were sent home for 7 nights with Philips Actiwatch Spectrum Plus. Data were analysed using Philips Actiware version 6. Using the mean of seven nights, TIB, total sleep time (TST), SE, sleep-onset latency (SOL) and wake after sleep onset (WASO) were examined. Compared to PSG, AUTO showed longer TIB and TST and less WASO. MARK only differed from PSG with decreased WASO. Differences between the PSG night and the following night at home were found, with better sleep on the first night home. Actigraphy in people with insomnia over seven nights is a valid indicator of sleep compared to an independent in-laboratory PSG. Event markers increased the validity of actigraphy, showing no difference in TIB, TST, SE and SOL. AUTO was representative of SE and SOL. Increased SE and TST without increased TIB suggests possible compensatory sleep the first at night home after in-laboratory PSG.


Subject(s)
Actigraphy/methods , Polysomnography/methods , Female , Humans , Male , Middle Aged , Sleep Initiation and Maintenance Disorders
11.
Psychol Med ; 49(3): 491-500, 2019 02.
Article in English | MEDLINE | ID: mdl-29792241

ABSTRACT

BACKGROUND: Insomnia and depression are highly comorbid and mutually exacerbate clinical trajectories and outcomes. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces both insomnia and depression severity, and can be delivered digitally. This could substantially increase the accessibility to CBT-I, which could reduce the health disparities related to insomnia; however, the efficacy of digital CBT-I (dCBT-I) across a range of demographic groups has not yet been adequately examined. This randomized placebo-controlled trial examined the efficacy of dCBT-I in reducing both insomnia and depression across a wide range of demographic groups. METHODS: Of 1358 individuals with insomnia randomized, a final sample of 358 were retained in the dCBT-I condition and 300 in the online sleep education condition. Severity of insomnia and depression was examined as a dependent variable. Race, socioeconomic status (SES; household income and education), gender, and age were also tested as independent moderators of treatment effects. RESULTS: The dCBT-I condition yielded greater reductions in both insomnia and depression severity than sleep education, with significantly higher rates of remission following treatment. Demographic variables (i.e. income, race, sex, age, education) were not significant moderators of the treatment effects, suggesting that dCBT-I is comparably efficacious across a wide range of demographic groups. Furthermore, while differences in attrition were found based on SES, attrition did not differ between white and black participants. CONCLUSIONS: Results provide evidence that the wide dissemination of dCBT-I may effectively target both insomnia and comorbid depression across a wide spectrum of the population.


Subject(s)
Cognitive Behavioral Therapy/methods , Depression/therapy , Sleep Initiation and Maintenance Disorders/therapy , Telemedicine/methods , Adult , Aged , Female , Humans , Linear Models , Male , Michigan , Middle Aged , Treatment Outcome
12.
J Clin Sleep Med ; 14(10): 1801-1804, 2018 10 15.
Article in English | MEDLINE | ID: mdl-30353818

ABSTRACT

ABSTRACT: We report a case series of four patients where tachypnea was observed during positive airway titration studies, double the baseline breathing rate (tachypnea range 46-68 breaths/min). It happened mainly during non-rapid eye movement to rapid eye movement sleep transitions without significant changes in oxygen saturation or signs of autonomic hyperactivity such as an increased heart rate. The increased respiratory rate may be a normal physiological extreme outlier seen during phasic rapid eye movement sleep triggered by high pressure ventilation and it may also indicate underlying ventilatory instability, making patients predisposed to central sleep apnea.


Subject(s)
Continuous Positive Airway Pressure/adverse effects , Tachypnea/etiology , Aged , Continuous Positive Airway Pressure/methods , Humans , Male , Middle Aged , Polysomnography , Sleep Stages
13.
J Clin Med ; 7(8)2018 Aug 08.
Article in English | MEDLINE | ID: mdl-30096830

ABSTRACT

Randomized controlled trials (RCTs) have eligibility criteria for the inclusion of participants. Ideally, the RCT sample would be representative for the patient population that will use the drug under investigation. However, external validity may be at stake when applying too many or too restrictive eligibility criteria. The current two-part study examined (1) the currently applied eligibility criteria in Phase II and III RCTs examining sleep medication; (2) how these criteria match with the insomnia population as a whole; and (3) how inclusion rates can be changed by an adaptation of these criteria. In the first study, insomnia RCTs were screened at www.clinicaltrials.gov, and relevant eligibility criteria were identified. The second study comprised a survey among self-reported insomnia patients. It was determined to what extent RCT eligibility criteria match the characteristics of this patient population. Of the n = 519 patients that completed the survey only n = 2 (0.4%) met all eligibility criteria of current RCTs. RCT enrolment criteria are not representative for the insomnia patient population as a whole. Being less rigorous in applying upper or lower criteria limits results in a significant increase in the number of eligible patients, and increases the representativeness of RCTs for the insomnia patient population as a whole. The current analysis demonstrates that is important to thoroughly reconsider the use eligibility criteria and their inclusion ranges, and to have a theoretical basis for using them.

14.
Sleep ; 41(8)2018 08 01.
Article in English | MEDLINE | ID: mdl-29762764

ABSTRACT

Study Objectives: To assess the risks associated with the use of alcohol as a "sleep aid," we evaluated tolerance development to pre-sleep ethanol's sedative-hypnotic effects, and subsequent ethanol dose escalation. Methods: Volunteers, 21-55 years old, with insomnia in otherwise good medical and psychiatric health and no history of alcoholism or drug abuse participated. In experiment 1 (n = 24) 0.0, 0.3, or 0.6 g/kg (n = 8 per dose) ethanol was administered before sleep and 8-hour nocturnal polysomnograms (NPSGs) were collected. In experiment 2, after six nights pretreatment with ethanol 0.45 g/kg (n = 6) versus placebo (n = 6), choice of pre-sleep ethanol or placebo was assessed over seven choice nights. Results: The 0.6 g/kg ethanol dose increased total sleep time and stage 3-4 sleep on night 2, but these effects were lost by night 6 (p < .05). Six nights of ethanol pretreatment produced on the choice nights more self-administered ethanol refills than the placebo pretreatment (p < .03). Conclusions: These are the first data to explicitly show the risks associated with the use of alcohol as a "sleep aid" among people with insomnia. Initially, a moderate dose of ethanol improved NPSG sleep, which was lost by night 6. Tolerance was associated with enhanced self-administration of pre-sleep ethanol.


Subject(s)
Alcoholism/etiology , Drug Tolerance/physiology , Ethanol/therapeutic use , Hypnotics and Sedatives/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Stages/drug effects , Sleep/drug effects , Adult , Ethanol/adverse effects , Female , Humans , Male , Middle Aged , Polysomnography , Sleep/physiology , Sleep Stages/physiology , Young Adult
15.
Sleep Med ; 33: 109-113, 2017 05.
Article in English | MEDLINE | ID: mdl-28449888

ABSTRACT

STUDY OBJECTIVES: To determine whether presurgery sleep extension in short-sleeping volunteers scheduled for total knee/hip replacement surgery would reduce postsurgery pain and analgesic use. METHODS: Eighteen short sleepers, defined by sleep times below the national mean (ie, ≤7 h) nightly, were randomized to one week of a 2-h nightly extension of their time in bed (EXT) or maintenance of their habitual time in bed (HAB) prior to knee or hip replacement surgery. Compliance was monitored by wrist actigraphy. Outcomes were the postsurgery daily dose of opiates (converted to morphine milligram equivalents) and the daily pain ratings (acquired 3-4 times across the day) on a 0-10 rating scale (0 = no pain to 10 = worst pain experienced) over the three to four day inpatient recovery. RESULTS: On a diary before the presurgery time in bed (TIB) manipulation, there were no significant differences in reported nightly sleep times between those randomized to the EXT group [6.0 (±0.78) h] and the HAB group [6.5 (±0.50) h]. During the one-week presurgery TIB manipulation, three participants failed to extend their TIB. Among those extending TIB (n = 7), compared to the HAB group, the EXT group spent significantly more nightly TIB (8.0 vs. 6.9 h, p < 0.05), which resulted in 1 h of more sleep (6.8 vs. 5.8 h, p < 0.04). On the three- to four-day postsurgery inpatient recovery, the EXT group reported significantly less average daily pain (4.4 vs. 5.6, p < 0.04) and less daily morphine milligram equivalent intake (20.3 vs. 38.6 mg, p < 0.02) than those by the HAB group. CONCLUSIONS: In this feasibility study, we found that a presurgery extended TIB and associated increase in sleep time in short-sleeping patients scheduled for undergoing joint replacement results in reduced postsurgery pain ratings and opiate use.


Subject(s)
Analgesics, Opioid/administration & dosage , Analgesics/administration & dosage , Arthroplasty, Replacement/adverse effects , Bed Rest/methods , Pain, Postoperative/drug therapy , Sleep/physiology , Actigraphy/methods , Aged , Analgesics/therapeutic use , Analgesics, Opioid/therapeutic use , Feasibility Studies , Female , Humans , Male , Middle Aged , Pain, Postoperative/classification , Pain, Postoperative/epidemiology , Pain, Postoperative/prevention & control , Preoperative Period
16.
Sleep ; 40(2)2017 Feb 01.
Article in English | MEDLINE | ID: mdl-28364510

ABSTRACT

Study objectives: To examine the real-world effectiveness of benzodiazepine receptor agonists (BzRAs) by quantifying response and remission rates in a clinical sample receiving chronic BzRA treatment for insomnia. Methods: Participants were outpatients (N = 193; 72% female; 55.2 ± 11.1 year) who had an insomnia diagnosis per medical records, and who were taking a therapeutic dose of BzRA for their insomnia. Endpoints were nocturnal sleep disturbance and Insomnia Severity Index (ISI) scores. A reduction meeting the criterion for the minimally important difference in ISI scores (change ≥ 6) constituted "response"; "remission" was inferred when symptoms fell below the clinical cutoff (ISI < 11). Results: Most participants (71%) used BzRAs at least 5 nights per week. Mean ISI scores were significantly lower (t = 22.31; p < .01) while on BzRAs than when untreated, but remained in the clinical range (mean = 11.0; standard deviation = 5.7). Although 76.7% responded to treatment, only 47.7% remitted. The majority (68.9%) of participants had a sleep-onset latency > 30 minutes and/or wake-time after sleep onset > 60 minutes while on BzRAs. After controlling for gender and insomnia severity when untreated, odds of insomnia persistence despite BzRA use were 2 times higher in patients with comorbid medical [odds ratio (OR) = 2.39; 95% confidence interval (CI) = 1.20% to 4.77%; p < .05] and psychiatric disorders (OR = 2.24; 95% CI = 1.21% to 4.13%; p < .05). Conclusions: This is the first study to distinguish between response and remission in insomnia patients taking BzRAs. Findings suggest that while many insomnia patients respond to chronic BzRA treatment, most do not remit. Remission rates are particularly low for comorbid insomnia, the most prevalent phenotype of the disorder.


Subject(s)
GABA-A Receptor Agonists/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Adult , Aged , Chronic Disease , Dose-Response Relationship, Drug , Female , Humans , Induction Chemotherapy , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Treatment Outcome
17.
Sleep ; 39(4): 825-32, 2016 Apr 01.
Article in English | MEDLINE | ID: mdl-26943472

ABSTRACT

STUDY OBJECTIVES: Despite mounting evidence for the overuse of prescription sleep aids (PSA), reliable data on PSA use among insomniacs are unavailable. Current studies focus on trends in PSA use at the general population level, and thus do not distinguish between transient sleep disturbance and insomnia disorder. Therefore, we prospectively examined the prevalence and predictors of baseline and chronic PSA use in a well-defined sample of individuals with insomnia. METHODS: We analyzed longitudinal data from an urban, community-based cohort of 649 adults (48.1 ± 11.6 y; 69.3% female) with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)-based insomnia disorder. Participants completed standardized measures of sleep disturbance, daytime alertness, depression, and anxiety at baseline and follow-up 1 y later. They also reported whether and with what frequency they used PSA at both time points. RESULTS: Approximately 19% of the sample used PSA at baseline, the majority (69.4%) of whom continued use 1 y later. Anxiety and daytime alertness were the only independent predictors of both acute and chronic PSA use. An increase of 1 standard deviation (SD) in alertness was associated with a 33% increase in the odds of chronic PSA use (χ(2) = 4.98; odds ratio [OR] = 1.33; 95% confidence interval [CI]: 1.04-1.72; P < 0.05), and a 1-SD increase in anxiety was associated with a 41% increase (χ(2) = 6.95; OR = 1.41; 95% CI: 1.09-1.82; P < 0.05). Chronic PSA users did not report any significant improvements in sleep from baseline to follow-up relative to nonusers. CONCLUSIONS: Hyperarousal, as indexed by daytime alertness and anxiety, is a strong determinant of PSA use among individuals with insomnia. These findings are consistent with emerging data showing that insomnia is not just a nocturnal sleep disorder, but one characterized by 24-h arousal. Though current research targets sleep disturbance, this study highlights the role of the arousal system in pharmacological treatment seeking.


Subject(s)
Arousal , Prescriptions/statistics & numerical data , Sleep Aids, Pharmaceutical/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/epidemiology , Anxiety , Attention , Depression , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Longitudinal Studies , Male , Middle Aged , Odds Ratio , Prevalence , Sleep , Sleep Aids, Pharmaceutical/administration & dosage , Sleep Initiation and Maintenance Disorders/diagnosis , Urban Health/statistics & numerical data
18.
J Clin Sleep Med ; 12(3): 319-25, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26446253

ABSTRACT

STUDY OBJECTIVES: Studies have shown pharmacokinetic differences for hypnotics in women compared to men, but few studies have assessed either short-or long-term differences in efficacy and safety. METHODS: To evaluate gender differences in the efficacy and safety of chronic nightly zolpidem (10 mg), we did a post hoc assessment of a large clinical trial. In the trial, participants with primary insomnia (n = 89), ages 23-70, meeting DSM-IV-TR criteria for primary insomnia were randomized, double blind, to nightly zolpidem, 10 mg (n = 47) or placebo (n = 42) 30 minutes before bedtime nightly for 12 months. Polysomnographic sleep on 2 nights in months 1 and 8 and likelihood of next-day sleepiness, rebound insomnia, and dose escalation were evaluated in months 1, 4, and 12. RESULTS: Relative to placebo, zolpidem significantly increased sleep efficiency and reduced sleep latency and wake after sleep onset assessed at months 1 and 8, with no differences in efficacy between women and men and no diminution of efficacy over months. On a next-day multiple sleep latency test (MSLT), no residual sedation was observed for either women or men. No rebound insomnia or dose escalation was seen with no gender differences in either. CONCLUSIONS: In adults with primary insomnia, nightly zolpidem administration showed no gender differences in acute or chronic efficacy or in next-day sleepiness. Zolpidem remained efficacious and safe across 12 months. CLINCIAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT01006525; Trial Name: Safety and Efficacy of Chronic Hypnotic Use; http://clinicaltrials.gov/ct2/show/NCT01006525.


Subject(s)
Hypnotics and Sedatives/therapeutic use , Pyridines/therapeutic use , Sleep Initiation and Maintenance Disorders/drug therapy , Adult , Aged , Double-Blind Method , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Hypnotics and Sedatives/adverse effects , Male , Middle Aged , Polysomnography/statistics & numerical data , Pyridines/adverse effects , Sex Factors , Sleep/drug effects , Treatment Outcome , Young Adult , Zolpidem
19.
Clin J Pain ; 32(4): 302-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26035524

ABSTRACT

OBJECTIVE: To investigate the differential nature of disturbed sleep in patients with fibromyalgia (FM) reporting sleep difficulties versus patients with primary insomnia (PI) and patients who do not report disturbed sleep (pain-free controls). MATERIALS AND METHODS: Patients (FM: n=132; PI: n=109; normals: n=52) were recruited for different studies. FM and PI patients were preselected to meet the sleep disturbance criteria. Patients with sleep or circadian disorders were excluded from all groups. Polysomnography was conducted at screening, during 2 consecutive nights. For this post hoc analysis of polysomnographies, length and frequency (duration, number) of wake and sleep bouts were analyzed, together with traditional sleep measures; a "bout"=consecutive 30-second epochs of sleep or wake. Data are mean±SD. RESULTS: FM and PI patients had decreased total sleep time and slow-wave sleep (SWS), and increased latency to persistent sleep (LPS) and wake time after sleep onset (WASO) versus controls (P<0.05 for each). FM versus PI patients had more SWS (48.1±32.4 vs. 27.2±23.6 min; P<0.0001) and shorter LPS (58.2±29.8 vs. 70.7±31.3 min; P=0.0055), but comparable WASO (107.7±32.8 vs. 108.6±31.5 min). Despite comparable WASO, FM patients had shorter (4.64±2.42 vs. 5.87±3.15 min; P=0.0016) but more frequent wake bouts versus PI patients (41.6±16.7 vs. 35.7±12.6; P=0.0075). Sleep bout duration was similar for FM (9.32±0.35 min) and PI patients (10.1±0.37 min); both populations had shorter sleep bout duration versus controls (15.7±0.7 min; P<0.0001 both). CONCLUSIONS: Increased frequency of wake and sleep bouts and decreased wake bout duration, together with decreased LPS and increased SWS, suggests that sleep in FM is characterized by an inability to maintain continuous sleep but a greater sleep drive compared with PI.


Subject(s)
Fibromyalgia/complications , Pain/physiopathology , Sleep Initiation and Maintenance Disorders/complications , Adolescent , Adult , Cohort Studies , Female , Humans , Male , Middle Aged , Polysomnography , Time Factors , Wakefulness , Young Adult
20.
Psychiatr Clin North Am ; 38(4): 793-803, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26600109

ABSTRACT

This article discusses the role sleep and alertness disturbance plays in the initiation, maintenance and relapse of substance use disorders.


Subject(s)
Sleep Wake Disorders/complications , Substance-Related Disorders/complications , Humans , Recurrence , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/drug therapy , Sleep Wake Disorders/therapy , Substance-Related Disorders/etiology , Substance-Related Disorders/psychology
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