Method for conducting clinical, psychological and laboratory studies of sleep disorders in patients with alcohol and opioid dependence

Abstract

FIELD: narcology.SUBSTANCE: used in clinical, psychological and laboratory studies of sleep disorders in patients with alcohol dependence and in patients with opioid dependence. The appointment includes a structured clinical interview and physical examination of the patient. Sociodemographic, clinical and anamnestic characteristics of patients are taken into account. Anhedonia is assessed using the Ferguson scale, with subscale scores calculated and the severity of anhedonia determined. In addition, sleep disorder symptoms are assessed using the Insomnia Severity Index and the Pittsburgh Sleep Quality Index. Objective sleep parameters are recorded using wrist actigraphs. In this case, the average values of total sleep time, sleep onset time, duration of slow-wave sleep, duration of REM sleep, and the ratio of slow-wave to REM sleep duration are noted. An analysis of the dynamics of sleep phases during observation is carried out. A patient diary is used. The severity of symptoms of depression and anxiety are assessed using psychological scales, as well as craving for psychoactive substances (PAS) using the Obsessive-Compulsive Drinking Scale, the Pennsylvania Alcohol Craving Scale, and the Visual Analogue Scale of Craving. Then a relapse of the disease is recorded. In addition, an assessment is made of the frequency and quantity of PAS using a retrospective analysis scale for the PAS use. A breath alcohol test and a urine drug test are used.EFFECT: method is accessible and allows for the identification of sleep disorders in patients with substance addictions, as well as the correction of any identified disorders.6 cl

Description

[0001] Technical field

[0002] The invention relates to the field of medicine, namely to narcology, and can be used to assess possible risk factors for relapse in patients with addiction to alcohol and other psychoactive substances (opiate addiction).

[0003] Technology Level

[0004] Analysis of studies on changes in sleep due to drug use convincingly demonstrates the need to identify and correct sleep disorders in drug addicts, as they affect both the quality of life and the duration and stability of remission in this group of patients.

[0005] The current level of technology in this area is characterized by:

[0006] See Asadullin AR et al. The role of sleep disorders and dysregulation of the melatoninergic system in the formation of alcohol use disorders. Narcology 2020; 19(3): 66-75. DOI: 10.25557 / 1682-8313.2020.03.66-75; Features of sleep disorders with the use of various psychoactive substances. Korsakov Journal of Neurology and Psychiatry 2020; (5): 153-159. DOI: 10.17116 / jnevro2020120051153; Prevalence of sleep disorders among patients with dependence on various psychoactive substances. Bulletin of Siberian Medicine 2020; (4): 26-35. DOI: 10.20538 / 1682-0363-2019-4-26-35; Efremov I.S. Alcohol and sleep disorders. Bekhterev Review of Psychiatry and Medical Psychology 2020; (3): 27-34. DOI: 10.31363 / 2313-7053-2020-3-27-34. and others).

[0007] A system and method for studying sleep are currently known under patent RU 2749068 C2. This group of inventions relates to medicine, specifically to a system and method for studying sleep. This involves monitoring a subject's physiological parameters during sleep and monitoring the subject's sleep phase using a set of sensors. From the output data of the set of sensors, a sensor malfunction or sensor disconnection is determined, requiring intervention in the subject's condition to maintain or repair the sleep study system. A processor determines, from the output data of the set of sensors, the subject's sleep phase and the time point for performing the intervention, depending on the subject's sleep phase. Output data is generated regarding the time point for performing the intervention that is minimally disturbing for the subject. This ensures effective sleep study with minimal impact on the patient's sleep by performing the intervention at the optimal time, i.e.,when the sleep phase reaches the preferred phase, in a manner that is less likely to awaken the patient and therefore does not potentially affect the sleep study results.

[0008] A method of non-invasive brain stimulation for sleep disorders in drug addiction is also known: treatment with transcranial magnetic stimulation from the article "Sleep disturbance in drug addiction: treatment with transcranial magnetic stimulation." Psychiatry, November 19, 2019. Addictive disorders Vol. 10 - 2019 / https: / / doi.org / 10.3389 / fpsyt.2019.00848. Patients sleep less and worse compared to the healthy control group. It is important to note that drug addicts are 5-10 times more likely to have sleep disorders than others. Drug abuse directly affects the quality of sleep in both current abusers and abstinent dependents; most drugs prolong the latency of sleep onset, reduce sleep efficiency and total sleep time. Sleep disturbances are common in drug addicts, ranging from opioids, methamphetamine, cannabis, and alcohol abusers.Drug addicts often have underlying medical conditions, including depression, bipolar disorder, and schizophrenia, and most of these patients experience sleep disturbances. People with sleep disturbances typically self-medicate with alcohol and sedatives, which, in turn, can contribute to drug abuse and increase the risk of relapse. Sleep disturbances are associated with negative mood, anxiety, and are often associated with additional medication use. Addressing sleep disturbances in drug addicts can be important for managing the severity of clinical symptoms and preventing relapse.

[0009] Also described to date is a method to study insomnia and PTSD over time in veterans receiving inpatient treatment for substance use disorders and PTSD. This method is described in the work of the University of California, San Diego 2019 Kolvonen, Peter J; Ellison, Jennifer; Haller, Moira; Norman, Sonya B. Publication: https: / / doi.org / 10.1080 / 15402002.2018.1425869. Background: Insomnia occurs in 66-90% of people with posttraumatic stress disorder (PTSD) and in 36-72% of people with substance use disorder (SUD). People with PTSD and SUD are more likely to have insomnia than people with either disorder alone. Insomnia is associated with worse treatment outcomes for both PTSD and SUD, increased daytime PTSD symptoms, and increased SUD relapse rates.Therefore, it is important to understand how sleep impacts the treatment of PTSD in patients with a dual diagnosis of SUD and how sleep changes over time in an inpatient SUD setting. Participants: Participants were 40 veterans with comorbid PTSD and community-based dysfunction who were enrolled in a 28-day Substance Abuse Rehabilitation Treatment Program (SARRTP) for PTSD.

[0010] Methods: The analysis used mixed models with time (baseline, post-treatment, 3-month follow-up) to examine PTSD and insomnia severity over time.

[0011] Results. Results of a longitudinal mixed model showed that PTSD symptoms improved over time, but insomnia symptoms did not. Although baseline insomnia did not influence subsequent PTSD symptoms, individuals with more severe insomnia at baseline had more severe baseline PTSD symptoms. However, there was no interaction between insomnia and PTSD severity over time, suggesting that baseline insomnia did not influence PTSD trajectories. Conclusions: These results are consistent with those from outpatient treatment for PTSD and provide further evidence that insomnia does not resolve without direct intervention.Given the association of insomnia with PTSD severity, SUD, and relapse, directly targeting insomnia may further help improve treatment outcomes for both PTSD and SUD.

[0012] The closest in technical essence solution chosen as the prototype object of this study is the method described in the article "Transdiagnostic group therapy for sleep and anxiety in adults with substance use disorders: protocol and pilot study." Psychiatry, March 29, 2023, Vol. 14 - 2023 / https: / / doi.org / 10.3389 / fpsyt.2023.1160001. Introduction: Treatment of substance use disorders (SUD) is challenging due to high rates of treatment dropout and relapse, particularly among individuals with comorbid mental illnesses. Anxiety and insomnia are common among patients with SUD and contribute to poor treatment outcomes. Interventions that simultaneously target anxiety and insomnia early in SUD treatment are lacking. To this end, we investigated the feasibility and preliminary efficacy of an empirically informed group-based transdiagnostic intervention, transdiagnostic SUD therapy, in a single-group pilot study to simultaneously reduce anxiety and improve sleep in adults receiving SUD treatment. Specifically, we hypothesized that participants would demonstrate reductions in anxiety and insomnia and improvements in sleep health, a holistic, multidimensional sleep-wake pattern that promotes well-being.The second aim was to describe a protocol for transdiagnostic treatment of SUDs and how it can be implemented in real-world addiction treatment settings.

[0014] Method: Participants were 163 adults (M age=43.23; 95.1%; 39.93% female) enrolled in an intensive outpatient SUD treatment program who attended at least three of four sessions of transdiagnostic SUD therapy. Participants had various SUDs (alcohol use disorder, 58.3%; opioid use disorder, 19.0%), and nearly one-third of the sample met criteria for two SUDs and comorbid mental health diagnoses (28.9% anxiety disorder, 24.6% major depressive disorder). Results: As expected, anxiety and insomnia significantly decreased from clinical to subclinical severity during the 4-week intervention period, and sleep quality also significantly improved (ps<0.001). These statistically significant improvements after transdiagnostic therapy for SUD demonstrated moderate to large effect sizes (ds>0.5).

[0016] Conclusion: Transdiagnostic SNS therapy is designed for flexible implementation in real-world clinical settings and, according to preliminary data, is effective in improving emotional and behavioral factors that increase the risk of relapse to substance use and poor SNS treatment outcomes. Further work is needed to replicate these results, determine the feasibility of widespread implementation of transdiagnostic SNS therapy, and examine whether treatment effects translate into improved substance use outcomes.

[0017] Participants (N = 274) were referred to the IOP at the Medical University of South Carolina (MUSC) Drug and Alcohol Problems Center (CDAP) after an initial pre-triage assessment and completion of detoxification, if needed. MUSC is a large academic medical center in the southeastern United States. The CDAP IOP is a 20-day program consisting of 3 hours of daily group therapy and weekly individual and family therapy. For more information on the IOP structure, please see Transdiagnostic SUD Therapy. Transdiagnostic SUD Therapy was integrated into the broader IOP programming; thus, all IOP patients had access to the Transdiagnostic SUD Therapy pilot trial if they attended IOP treatment on the day it was provided. Specifically, every Tuesday during the study period, a 90-minute sleep module was presented, followed by a 90-minute anxiety-focused module.There were no exclusion criteria for participation in the study, as all patients enrolled in the broader IOP clinic participated in this group therapy if they attended on Tuesdays. The open-label study ran from January 2017 to April 2019 and was terminated due to changes in the organizational structure of the IOP clinic.

[0018] A retrospective chart review was conducted to collect relevant information. Before starting the IOP, participants provided demographic information and participated in an interview to assess their substance use history, medical and psychiatric history, and social history. At the beginning of each sleep module, participants were asked to complete a self-assessment of insomnia and sleep health, and at the beginning of each anxiety module, participants were asked to complete a self-assessment of anxiety severity.

[0019] The technical challenge addressed by this study, which could not be addressed by analogs, particularly the prototype, was the use of not only clinical and psychodiagnostic methods but also the inclusion of a laboratory method—actigraphy—in the research arsenal. Sleep disturbances are common among patients with mental and behavioral disorders associated with psychoactive substance use, both during periods of active use and during periods of withdrawal and abstinence. This method takes into account the specific characteristics of sleep disturbances associated with the use of psychoactive substances such as alcohol and opioids.

[0020] The object of this study is a comprehensive method for conducting a clinical-psychological and laboratory study of sleep disorders in patients with alcohol and opioid addiction, which includes both the use of psychodiagnostic questionnaires and methods for objectifying the obtained data - wrist actigraphy.

[0021] The technical result achieved by this method involves the use of not only clinical and psychodiagnostic methods but also the inclusion of a laboratory method—actigraphy—into the research arsenal. This technical result allows for a more comprehensive and objective assessment of sleep disorders in patients with alcohol and opioid addiction.

[0022] By using wrist-worn actigraphs, the study is able to account for the specific characteristics of sleep disorders associated with psychoactive substance use, such as alcohol and opioids. This method provides more accurate and objective data on patients' sleep compared to traditional clinical methods.

[0023] Previous studies validating the use of wrist-worn devices in clinical trials indicate high measurement accuracy with hand-held actigraphy, comparable to classical polysomnography.

[0024] Implementation of the invention

[0025] A method for conducting a clinical, psychological, and laboratory study of sleep disorders in patients with alcohol and other psychoactive substance dependence. Sleep parameters were assessed based on self-report and actigraphy. Data were obtained, including information on the nature of sleep disorders depending on: 1) the phase of the addictive cycle, 2) the severity of comorbid psychological symptoms, and 3) the anamnestic and current clinical characteristics of the addictive disorder. To assess the patients' condition the following were used: 1) Wrist actigraphy, 2) Questionnaires for subjective assessment of sleep: the insomnia severity index and the sleep quality index (Pittsburgh questionnaire), 3) Structural clinical interview and physical examination, 4) Clinical assessment scale (Clinical Global Impression Scale), 5) Psychological scales for assessing the severity of the symptom of depression and the severity of the symptom of anxiety, the Montgomery and Asberg scale and the Hamilton anxiety scale,6) Scales for assessing current clinical symptoms (the Ferguson Anhedonia Scale will be used to assess the patient's anhedonia), 7) The following were used to assess craving for psychoactive substances: the Obsessive-Compulsive Alcohol Craving Scale, the Pennsylvania Alcohol Craving Scale, the Visual Analogue Scale, 8) Registration of disease relapse, 9) An assessment of the frequency and quantity of psychoactive substances used was conducted using the Retrospective Analysis Scale of Psychoactive Substance Use, 10) Objective methods for assessing psychoactive substance use. A breath alcohol test was used to determine the resumption of alcohol consumption. A urine drug test was used to determine drug use, 11) Patient diary. 30 participants completed all procedures of the 3-month study period, which involved weekly visits to the research center for a comprehensive assessment.

[0026] The patients' condition was compared at the inclusion visit and over time. The following parameters were used to assess nighttime sleep: total sleep time, REM sleep period, and slow wave sleep period. It was found that satisfaction with health status was significantly lower in the AG group: 42.24 (18.51) versus 65.38 (11.40) in the MG group (p≤0.001). However, in the MG group, more patients (38.5%) sought treatment for somatic problems than in the AG group (18.51) (p=0.023). According to the expert assessment of the research physician (Clinical Global Impression scale), a "more significant" severity of drug addiction was detected more often in the AG group (26.5%) than in the MG group (7.7%). For the first time, it was shown that in the early stages of remission, a moderate and strong decrease in “interest in life” and “pleasure” on the anhedonia scale was noted in the majority of patients in the AG (61.2% and 59.2%, respectively), while for the majority of OG the decrease was mild (53.8% and 61.5%, respectively) (p≤0.001).In both groups, anxiety symptoms were identified in the last 30 days: the average Hamilton anxiety scale score in the total sample was 13.63 (5.41), with no significant difference between the groups.

[0027] The dynamics of qualitative and quantitative characteristics of sleep was assessed. The average duration of nighttime sleep according to the survey was 5.68 hours (95% CI 5.46-5.90 hours), according to the questionnaires - 6.07 hours (95% CI 5.49-6.25 hours). For the first time, when comparing the duration of sleep between groups of patients with alcoholism and opioid addiction, no reliable differences were found between the indicators: 5.72 (5.50-5.93) and 5.62 (5.10-6.13), respectively. The duration of falling asleep is longer in participants in the AG M = 73.78 minutes (95% CI 64.12-83.43) versus 65.38 minutes (54.05-76.72) in the MG, but the difference is not significant. However, the duration of time spent in bed per night was significantly longer in the AG participants 7.98 (7.73-8.23) than in the MG 7.09 (6.53-7.64). The average duration of nighttime sleep according to subjective assessment was 6.09 h (95% CI 5.79-6.38 h), and according to actigraphy data it was 6.07 h (95% CI 5.49-6.25 h).New data were obtained by comparing sleep duration between groups of patients with alcoholism and opioid addiction: no reliable differences were found between subjective and objective indicators: according to the survey (6.07 (5.73-6.41) in the AG versus 6.11 (5.53-6.69) in the MG) and according to actigraphy data (6.04 (5.39-6.28) in the AG versus 6.13 (5.47-6.39) in the MG). In the two studied nosological groups, it was revealed that the sleep quality indicator tended to decrease after a week of abstinence from psychoactive substances (p<0.001). Original data were obtained: the total sleep amount indicators obtained during the survey and from actigraphy devices correlated with each other (r=-0.405, p<0.01).

[0028] Thus, the objectified data correspond to clinical data on the persistence of sleep disorders during the early post-abstinence period, which is associated with a violation of the circadian regulation of cortisol secretion due to dysregulation of the pituitary-hypothalamic and sympathoadrenal systems during the period of withdrawal syndrome (normalization of cortisol levels occurs only on days 21-28 after the relief of withdrawal syndrome). At inclusion, the sleep quality index (SQI) was higher than 5 points in all patients participating in the study, indicating low sleep quality. It is worth noting that no differences in SQI scores were found between the groups at the study entry and exit points: in patients with AZ, the mean value at the first measurement was 19.3 (standard deviation, SD = 4.2) points, in patients with OD it was 16.9 (SD = 3.2), while at the final visit, the scores were 2.2 (SD = 1.9) and 0.0 points, respectively. However, throughout the study, bedtime was significantly later in the opioid-dependent group. In the OD group, the total amount of sleep time was statistically significantly less compared to the AZ group, but significant differences emerged only starting from the 6th week, that is, in the later observation period.Sleep quality and sleep duration were found to vary significantly over time: the overall sleep quality score decreased (a decrease in the overall sleep quality score indicates an improvement in sleep quality), and the number of hours of sleep increased with an unchanged bedtime, which led to the conclusion that sleep quality gradually improved during the period of remission while maintaining a stable sleep pattern. Similar dynamics were observed in the actigraph data: in both groups, the duration of slow-wave sleep and REM sleep gradually increased during the observation period (p<0.001). The proportion of slow-wave sleep in total sleep time did not change statistically significantly over time (p=0.06); however, in the AZ group, the percentage of slow-wave sleep was significantly lower compared to the 3D group (p=0.004). The ratio of slow-wave sleep to REM sleep increased over time (p=0.002) in both groups, but was higher in the 3D group (p=0.01).

[0029] Thus, the dynamics of changes in quantitative sleep indicators indicated a gradual restoration of sleep structure in two groups of patients, provided they abstained from psychoactive substance use. The impact of sleep quality on the course of addictive disorder was assessed. According to the results of assessing the impact of the general sleep quality score (GSQS) on patient dropout from the study (missing a follow-up visit or breakdown / relapse), it was found that with an increase in the GSQS indicator by 1 point, the risk of dropout increases by 13.8% (95% CI 1.10; 1.17) in the total sample, by 10.7% (95% CI 1.06; 1.16) in the OZ group, and by 17.2% in the AZ group (95% CI 1.12; 1.22). In patients with low sleep quality (OBCS score greater than 5), compared with participants with higher sleep quality (OBCS score equal to 5 or less), the risk of dropping out of the study was 5.4 times higher (95% CI 3.22; 9.08) in the overall sample, 2.4 times (95% CI 1.09; 5.12) in the OZ group, and 8.6 times higher in the AZ group (95% CI 4.27; 17.31).The association between poor sleep quality and the incidence of breakdown / relapse / dropout was more pronounced among patients in the AZ group (odds ratio (OR) = 8.60; 95% CI 4.27; 17.30) compared with patients in the OZ group (OR = 2.37; 95% CI 1.10; 5.17). The influence of objective sleep indicators on the course of addictive disorder was assessed.

[0030] In the AZ group, a statistically significant trend towards a higher risk of dropout (OR=2.01; 95% CI 1.00; 4.06) was revealed among patients whose sleep onset time was after 12:00 a.m. In the OZ group, a later sleep onset time was significantly associated with relapse (OR=11.23; 95% CI 3.05; 41.27). The survival curves in the two groups of subjects by the categorical indicator “sleep onset time” are presented in Figures 4a and 4b. According to the results of Cox regression, it was possible to establish a significant effect of sleep parameters on the probability of failure, relapse, or dropout in the AZ group. The risk of relapse in the AZ group decreased by 41% (95% CI 0.4; 0.8; p-value <0.001) with an increase in the duration of total sleep time, by 52.9% (95% CI 0.3; 0.7; p-value <0.001) with an increase in the duration of slow-wave sleep, and by 74.8% (95% CI 0.1; 0.5; p-value <0.001) with an increase in the proportion of slow-wave sleep to REM sleep.

[0031] The impact of sleep quality on anhedonia was assessed in a general cohort. A correlation was found between low sleep quality and the anhedonia subscales of lack of interest (F=46.85, p<0.001) and enjoyment of life (F=52.84, p<0.001). When comparing the groups by the severity of anhedonia (according to the two subscales), it was found that lower sleep quality (i.e., a higher OBCS value) was associated with more severe anhedonia. For example, the OBCS score in the group of patients without anhedonia (according to the "interest in life" subscale) was, on average, 6 points lower compared to the group of participants with mild anhedonia, and for the "enjoyment of life" score, the difference between these groups was 7 points. When comparing the OBCS index in groups of patients with mild and moderate anhedonia, the difference was 5 points on the “interest in life” subscale and 4 points on the “pleasure of life” subscale.A difference in the OBCS score between the groups of patients with moderate and severe anhedonia was found only for the "interest in life" subscale. A significant decrease in the OBCS score was found within one week of observation: the difference between Visits 1 and 2 was 3 points for both subscales ("interest in life" and "pleasure"). Furthermore, a significant decrease in the OBCS score was found at Visit 4 compared to Visit 3: the difference was approximately 2 points for the "lack of interest in life" and "pleasure in life" subscales. This pattern reflects a gradual improvement in sleep quality over time, provided that remission was maintained in the overall sample, regardless of the severity of the addiction.

[0032] Disclosure of invention

[0033] The technical result achieved by this invention is to improve the accuracy of sleep assessment in patients with alcohol dependence syndrome and opioid addiction by developing a comprehensive approach that incorporates clinical and psychodiagnostic methods, as well as laboratory testing. This approach will enable accurate diagnosis of sleep quality disturbances, which can be a predictor of relapse or relapse in patients with alcohol and opioid addiction.

Claims

1. A method for conducting a clinical, psychological and laboratory study of sleep disorders in patients with alcohol dependence and in patients with opioid dependence, which involves a structured clinical interview and physical examination with the collection of sociodemographic, clinical and anamnestic characteristics of the participants, assessing anhedonia using the Ferguson scale with scoring on subscales and determining the severity of anhedonia, assessing the symptoms of sleep disorders using the insomnia severity index and the Pittsburgh sleep quality index, recording objective sleep indicators using wrist actigraphs to obtain average values ​​​​of total sleep time, sleep onset time, duration of slow sleep, duration of REM sleep and the ratio of the duration of slow sleep to REM, analyzing the dynamics of sleep phases over the observation time, using a patient diary,The severity of symptoms of depression and anxiety are assessed using psychological scales, craving for psychoactive substances is assessed, relapse of the disease is recorded, the frequency and quantity of psychoactive substance used is assessed using the scale of retrospective analysis of psychoactive substance use, a breath alcohol test is used to determine the resumption of alcohol consumption, and a urine drug test is used to determine drug use.

2. The method according to paragraph 1, characterized in that the degree of severity of anhedonia is classified as mild, moderate and severe.

3. The method according to claim 1, characterized in that a modified insomnia severity index is used to assess the symptoms of sleep disorders at the inclusion stage, including difficulty falling asleep, difficulty maintaining sleep, early awakening, daytime sleepiness, and lack of vigor upon awakening.

4. The method according to paragraph 1, characterized in that the assessment of sleep quality according to the Pittsburgh Sleep Quality Index is carried out dynamically during observation visits.

5. The method according to claim 1, characterized in that at least the total sleep time, the period of the REM sleep phase, and the period of the slow sleep phase are used as indicators of night sleep.

6. The method according to paragraph 1, characterized in that the obsessive-compulsive scale of craving for psychoactive substances, the Pennsylvania scale of craving for alcohol and the visual analogue scale of craving for psychoactive substances are used to assess the craving for psychoactive substances.