ORIGINAL RESEARCH published: 17 November 2020 doi: 10.3389/fpsyt.2020.540022 Insomnia Symptoms in Patients With Substance Use Disorders During Detoxification and Associated Clinical Features Lara Grau-López 1,2,3,4*, Laia Grau-López 5 , Constanza Daigre 2,3,4 , Raúl Felipe Palma-Álvarez 1,2,3,4 , Nieves Martínez-Luna 1,2,3,4 , Elena Ros-Cucurull 1,2,3,4 , Jose Antonio Ramos-Quiroga 1,2,3,4 and Carlos Roncero 6,7 1 Department of Psychiatry, Hospital Universitari Vall d’Hebron, Barcelona, Spain, 2 Group of Psychiatry, Mental Health and Addiction, Vall d’Hebron Research Institute, Barcelona, Spain, 3 Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain, 4 Department of Psychiatry and Forensic Medicine, Autonomous University of Barcelona, Barcelona, Spain, 5 Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Badalona, Spain, 6 Psychiatric Edited by: Service, University of Salamanca Health Care Complex, Institute of Biomedicine of Salamanca, University of Salamanca, Holly Moore, Salamanca, Spain, 7 Psychiatric Unit, School of Medicine University of Salamanca, Salamanca, Spain National Institute on Drug Abuse (NIDA), United States Reviewed by: Background: Insomnia is highly prevalent in patients with substance use disorders Chiara Montemitro, (SUD), and it has been related to a worse course of addiction. Insomnia during University of Studies G. d’Annunzio detoxification in a hospital has not been adequately studied. This study aims to compare Chieti and Pescara, Italy Alessio Simonetti, sociodemographic, clinical, and psychopathological characteristics of SUD patients Baylor College of Medicine, undergoing a detoxification program, by comorbidity and insomnia symptoms. United States *Correspondence: Methodology: We recruited 481 patients who received pharmacological and Lara Grau-López psychotherapeutic treatment for detoxification. They were evaluated through lgrau@vhebron.net semi-structured interviews, standardized questionnaires, and a specific sleep log. Specialty section: A bivariate and multivariate analysis of the data was performed. This article was submitted to Results: Insomnia was reported by 66.5% patients, with sleep-maintenance insomnia Addictive Disorders, a section of the journal the most frequent issue, followed by early morning awakening and sleep-onset insomnia. Frontiers in Psychiatry Patients with alcohol use disorder and cannabis use disorder had higher prevalence Received: 03 March 2020 of sleep-onset insomnia. Patients with cocaine and heroin use disorder had higher Accepted: 15 October 2020 prevalence of sleep-maintenance insomnia. Independent factors that allowed the Published: 17 November 2020 identification of insomnia symptoms included being female (OR: 3.43), polysubstance use Citation: Grau-López L, Grau-López L, (OR: 2.85), comorbid anxiety disorder (OR: 2.02), and prior admission for detoxification Daigre C, Palma-Álvarez RF, (OR: 1.22). Martínez-Luna N, Ros-Cucurull E, Ramos-Quiroga JA and Roncero C Conclusions: Insomnia symptoms are very prevalent in patients admitted for (2020) Insomnia Symptoms in detoxification. The diagnosis and therapeutic strategies for the insomnia symptoms Patients With Substance Use Disorders During Detoxification and should be improved, especially in women and in patients with greater addiction severity Associated Clinical Features. and with anxiety disorders. Front. Psychiatry 11:540022. doi: 10.3389/fpsyt.2020.540022 Keywords: addiction, insomnia, sleep disorders, women, detoxification process, anxiety disorders Frontiers in Psychiatry | www.frontiersin.org 1 November 2020 | Volume 11 | Article 540022 Grau-López et al. Insomnia in Addicted Patients INTRODUCTION The inclusion criteria were substance dependence (excluding primary abuse of caffeine or nicotine) in the past year according Insomnia has been defined as a sleep disorder characterized to DSM criteria, active consumption up to the day before by difficulty with sleep initiation, duration, consolidation, admission to the detoxification unit, and provision of signed or quality that occurs despite circumstances favorable for informed consent to participate in the study. The exclusion sleeping. In addition, there could be daytime impairment criteria were failure to complete the detoxification program symptoms, including fatigue, sleepiness, mood disturbances, and presence of a major language barrier or severe cognitive physical symptoms and concerns about or dissatisfaction with impairment. The study was approved by the Vall d’Hebron sleep (1). Hospital ethics committee, according to the (29). Insomnia is estimated to affect between 20 and 35% of the general population (2–6) and 40–90% of patients with Procedure psychiatric disorders other than addictions (7–10). Individuals Patients received appropriate detoxification treatment for their with substance use disorders (SUD) also have a higher SUD. The treatment in all cases consisted of pharmacologic prevalence of insomnia than the general population (11, 12). and psychological interventions to treat SUD (detoxification) The relationship is bidirectional; people with insomnia are also and psychiatry comorbidity. They received decreasing doses more prone to SUD (13–15). Insomnia is suffered by between 30 of benzodiazepines (regardless of the substance that led to and 85% of SUD patients, depending on the primary substance admission) and adjuvant medications to treat comorbid of abuse and other methodological factors (16–19). Alcohol psychiatric symptoms. Patients participated in group use disorder is the problem most studied regarding insomnia psychotherapy during the detoxification program, which symptoms, and the rates described for those patients are between consisted of three sessions including psychoeducation, a 30 and 60% (20–22). Sleep in this population is influenced by motivation interview, and prevention of substance addiction numerous substance use-related factors, such as type and amount relapse. Hospital stays ranged between 10 and 15 days (10.9 of drug used, duration of addiction, route of administration, state ± 3.2). of intoxication or withdrawal, and simultaneous consumption of The assessment process consisted of an evaluation of insomnia stimulants and depressants. symptoms conducted by daily interviews with a psychiatrist In the general population, insomnia is more likely to and through information from sleep logs kept by night-shift affect women, people over 65 years old, and shift and nurses. In addition, three interviews conducted by psychologists night workers (23–25). Likewise, patients with medical and following the protocol to evaluate comorbidity were done. psychiatric comorbidities are more susceptible to nocturnal sleep disturbances (4, 7). Study Variables and Instruments Insomnia has been linked to a worsening of addiction (26, 27); The variables recorded were insomnia symptoms, however, few studies have analyzed risk factors for insomnia in sociodemographics, substance consumption variables, and patients with SUD. It has been identified that comorbid anxiety medical and psychiatric comorbidities. disorder, medical comorbidities, and early onset of dependence The presence of symptoms of insomnia was evaluated by increase the risk of insomnia during active substance use (28). the psychiatrist according to clinical criteria, based on daily Detoxification is frequently required among SUD patients, interviews and complementary information from a sleep log. who could be done in an outpatient or hospital setting. The sleep log is a tool where the night-shift nurses recorded The detoxification process is a critical time to evaluate and how each patient slept for each hour between 11 p.m. and propose therapeutic approaches, including insomnia symptoms. 7 a.m. was considered in order to diagnose insomnia symptoms It has been found that symptoms of insomnia during a (Figure 1). A distinction was made between the following types detoxification process are a risk factor to early relapses (26). of insomnia: sleep-onset insomnia (failure to fall asleep within To our knowledge, however, risk factors of insomnia symptoms the first half hour of going to bed), sleep-maintenance insomnia during detoxification process have not been described. Therefore, (two or more awakenings a night), early awakening (awakening this study aimed to compare sociodemographic, clinical, and at least 1 h before the usual time), poor sleep quality (none of the psychopathological characteristics of SUD patients undergoing above but presence of diurnal effects, such as daytime sleepiness, a detoxification program according to the presence/absence of fatigue, irritability, nervousness, decreased concentration, muscle insomnia symptoms. It was hypothesized that symptoms of tension, and headache). insomnia would be common in this population and that patients Patients who were diagnosed with insomnia symptoms were with insomnia symptoms would have higher rates of psychiatric prescribed specific treatment according to their profile and the comorbidity and more severe addiction. judgment of the clinicians responsible for their care. Psychiatric comorbidity was evaluated using semi-structural METHODS AND MATERIALS diagnostic interviews. SCID-I (Structured Clinical Interview for the DSM-IV Axis I Disorders), SCID-II (Structured Clinical Participants Interview for the DSM-IV Axis II Disorders), and CAADID In this study 481 SUD inpatients participated in the detoxification (Conners’ Adult ADHD Diagnostic Interview for DSM-IV) unit of Vall d’Hebron University Hospital in Barcelona, Spain. were used to diagnose attention deficit hyperactivity disorder The recruitment period was from June 2013 to May 2018. (ADHD). Urinalysis and alcohol breath test results were used Frontiers in Psychiatry | www.frontiersin.org 2 November 2020 | Volume 11 | Article 540022 Grau-López et al. Insomnia in Addicted Patients FIGURE 1 | Nighttime sleep log. S, sleep; A, awake (>30 min); W, wake up (minutes). to evaluate substance consumption at the first day of the Table 1 summarizes the sociodemographic, clinical, and detoxification process. treatment characteristics of the sample. The most common primary substance of use was alcohol (42.4%), followed by cocaine (32.8%), opiates (12.9%), cannabis (7.1%), and Statistical Analysis benzodiazepines (4.8%). Polysubstance dependence (three First of all, the main variables of the sample were analyzed substance use disorders within the past 12 months) was reported using descriptive statistics (mean, standard deviation, and for 46.4% patients. Polysubstance dependence (three substance frequency tables) and bivariate analyses. Later, in order to use disorders within the past 12 months) was reported for 46.4% conduct comparisons, the sample was divided into two groups patients. The distribution of substance consumption across the (patients with insomnia symptoms vs. patients without insomnia lifespan of the polysubstance dependent patients was 85.8% symptoms). The chi-square test was used to compare categorical cocaine, 77.7% alcohol, 75.2% cannabis, 56.7% opioids, and variables between these groups, while Student’s t-test was used to 54.1% benzodiazepines. compare continuous variables. Afterward, to reduce false positive Insomnia symptoms were reported by 66.5% of patients (n results, a Bonferroni correction for multiple tests was applied = 320) during the detoxification process and 84.3% reported according to the number of tests in each bivariate analysis. previous insomnia symptoms. Sleep-maintenance insomnia was Variables that retained statistical significance after Bonferroni the most common type of insomnia overall, followed by early correction were included in the multivariate analysis. Finally, morning awakening, sleep-onset insomnia, and poor quality logistic regression, with the enter method, was used to identify of nocturnal sleep. At discharge, insomnia symptoms were the independent effect of the variables of the insomnia symptoms considered to have been alleviated in 63.8% of patients (present of insomnia = 1). Data were entered and analyzed in On the other hand, the relationship among type of insomnia SPSS version 18.0. In all cases, statistical significance was set at symptoms and main SUD was analyzed. Patients with alcohol p < 0.05. use disorder had higher prevalence of sleep-onset insomnia (44.7 vs. 30.8%, p < 0.02), early awakening (45.4 vs. 33.6%, p < 0.02) and poor sleep quality (44.2 vs. 11.5%, p < 0.001) than other RESULTS SUD patients. Patients with cocaine use disorder had higher Description of the Sample rates of sleep-maintenance insomnia (37.5 vs. 27.2%, p < 0.02) A total of 552 patients were admitted to the detoxification and poor sleep quality (57.7 vs. 31.4%, p < 0.006). Patients unit during the study period. Fifty patients requested voluntary with heroin use disorder were more likely to experience sleep- discharge before completion of the program, and 21 were maintenance insomnia (21.2 vs. 6.1%, p < 0.0001). Finally, not included because of language barriers or severe cognitive patients with cannabis use disorder had higher prevalence of impairment. Hence, the final sample consisted of 481 patients. sleep-onset insomnia (14.1 vs. 5.7%, p < 0.008), while patients Frontiers in Psychiatry | www.frontiersin.org 3 November 2020 | Volume 11 | Article 540022 Grau-López et al. Insomnia in Addicted Patients TABLE 1 | Description of study participants. Sociodemographic variables Total (n = 481) Total (n = 481) Age (years) 40.9 ± 10.3 Employed (working) 16.2% Gender (male) 72.3% Marital status (married) 33.1% Nationality (foreign) 9.8% Living with someone 34.1% Education (primary education) 66.7% Criminal record (prison) 20.6% Clinical variables related to comorbidities Medical history 60.7% Axis II disorders 44.7% Psychiatric history 62.2% Cluster B 28.7% Axis I disorders 43.7% Other personality disorder 9.3% Anxiety disorder 15.6% Cluster C 4.8% Depressive disorder 14.1% Cluster A 1.9% Attention deficit hyperactivity disorder 13.1% Psychotic disorder 8.5% Prior psychiatric admissions 15.6% Bipolar disorder 3.1% Clinical variables related to consumption Age at start of consumption 17.8 ± 6.4 Polysubstance users 46.4% Age at onset of substance use disorder 24.1 ± 8.2 Binge consumption prior to admission 55.3% Years of addiction 16.6 ± 11.3 Positive breath alcohol test on admission 25.2% Main Substance Use Disorder Positive urinalysis on admission 55.9% Alcohol 42.4% Prior detoxification admissions 52% Cocaine 32.8% Heroine 12.9% Cannabis 7.1% Benzodiazepines 4.8% Psychopharmacological and Psychological treatment Antiepileptic 69% ADHD drugs 4.7% Antidepressant 60.1% Opioid agonists 12.9% Antipsychotic 44.9% Disulfiram/Namelfeno 20.8% Benzodiazepines 6.9% Group Psychotherapy 81.1% Insomnia symptoms No insomnia symptoms during detoxification process 33.5% Type of insomnia Sleep-maintenance insomnia 45.1% Early morning awakening 25.4% Insomnia symptoms during detoxification process 66.5% Sleep-onset insomnia 16.4% Poor quality of nocturnal sleep 12.3% with benzodiazepine use disorder had higher prevalence of admissions for detoxification more were found frequently (see sleep-maintenance insomnia (8.3 vs. 1.9%, p < 0.001) and Table 2). early awakening (8.2 vs. 3.6%, p < 0.04) than patients with The following variables were included in the logistic other SUD. regression analysis after Bonferroni correction: gender (female), polysubstance users, anxiety disorder, prior admission for detoxification, admission for heroin detoxification, and cluster Insomnia Symptoms According to B personality disorder. Independent factors that allowed for Sociodemographic and Clinical Variables identification of insomnia symptoms were female, polysubstance As is shown in Table 2, insomnia symptoms were more use, prior admission for detoxification, and comorbid anxiety frequently present in women and older individuals. Patients disorder. Women were 3.43 times more likely to suffer from with heroin use disorders had significantly more insomnia insomnia. Patients with a history of polysubstance use were symptoms than patients with another substance use disorders. 2.85 times more likely more likely to suffer from insomnia, Also, polysubstance users and patients with medical conditions and patients with anxiety disorders were 2.02 times more likely had significantly more insomnia symptoms. When comorbidity to suffer from insomnia. Finally, patients with history of prior psychiatry was compared for insomnia symptoms, that anxiety admission for detoxification were 1.22 times more likely to suffer disorders, ADHD, cluster B personality disorder, and prior from insomnia during the detoxification process (see Table 3). Frontiers in Psychiatry | www.frontiersin.org 4 November 2020 | Volume 11 | Article 540022 Grau-López et al. Insomnia in Addicted Patients TABLE 2 | Insomnia symptoms according to sociodemographic and clinical variables during detoxification process. Sociodemographic variables Insomnia symptoms (n = 320) No insomnia symptoms (n = 161) p Age (years) 44.4 ± 11.8 40.2 ± 9.3 0.04* Gender (female) 34.7 13.7 0.0001*, ** Nationality (foreign) 9.1 11.2 0.46 Education (primary education) 32.5 34.8 0.62 Employed (working) 88.3 86.6 0.52 Marital status (married) 30.3 38.5 0.07 Living with someone 30.6 31 0.21 Criminal record (prison) 24.9 23.4 0.78 Clinical variables related to comorbidities Medical history 64.7 52.8 0.01* Psychiatric history 68.1 60.3 0.10 Axis I 49.4 42.3 0.18 Anxiety disorder 19.4 8.1 0.001*, ** Depressive disorder 19.6 16.6 0.32 Attention deficit hyperactivity disorder 15.3 8.7 0.04* Psychotic disorder 8.4 8.7 0.92 Bipolar disorder 3.8 1.9 0.26 Axis II 51.6 43.1 0.09 Cluster B 33.1 19.9 0.002*, ** Other personality disorder 11.6 10.1 0.81 Cluster C 5 4.3 0.75 Cluster A 1.9 1.9 0.99 Prior psychiatric admissions 26.8 20 0.09 Clinical variables related to consumption Age at start of consumption 17.9 ± 6.4 17.5 ± 6.4 0.44 Age of onset of substance use disorder 24.3 ± 8.04 23.8 ± 8.6 0.55 Years of addiction 19.6 ± 10.2 18.6 ± 13.0 0.87 Main Substance Use Disorder % % Alcohol 57.8 51.6 0.40 Cocaine 31.9 34.8 0.52 Heroine 16.6 5.6 0.001*, ** Cannabis 6.6 8.1 0.54 Benzodiazepines 7.2 5.2 0.11 Polysubstance users 56.6 26.1 0.0001*, ** Prior detoxification admissions 59.7 36.6 0.0001*, ** Binge consumption prior to admission 53.3 53.3 0.99 Positive breath alcohol test 23.8 28 0.32 Positive urinalysis 61.3 55.3 0.08 Psychopharmacological and psychological treatment Antiepileptic 71.3 82.2 0.45 Antidepressant 59.3 76.3 0.38 Antipsychotic 45.3 57.2 0.21 Benzodiazepines 6.9 6.8 0.986 Opioid agonists 9.3 16.3 0.08 Interdictors 17.9 23.8 0.73 *p < 0.05; **Statistically significant after Bonferroni correction. DISCUSSION to a hospital detoxification unit. This rate is higher than the rates of 20–35% reported for the general population (2– We detected a high prevalence of insomnia symptoms (66.5%) 6) and similar to rates described for patients with other in the early stages of substance withdrawal in patients admitted psychiatric disorders (7–10, 30–32). In a previous study, we Frontiers in Psychiatry | www.frontiersin.org 5 November 2020 | Volume 11 | Article 540022 Grau-López et al. Insomnia in Addicted Patients TABLE 3 | Variables independently associated with insomnia symptoms during were also more likely to experience insomnia symptoms. These detoxification process. two factors can be considered as indicators of addiction severity OR 95% CI p that are closely associated with insomnia symptoms; therefore, insomnia could be a frequent symptom in patients with worse Gender (female) 3.43 2.01–5.86 0.0001 addiction treatment outcomes. In line with this, it is coherent Polysubstance users 2.85 1.79–4.54 0.0001 that insomnia has been associated with early relapses in both Anxiety disorder comorbidity 2.09 1.06–4.12 0.03 alcohol use disorders and illegal substance use disorders patients Prior admission for detoxification 1.22 1.07–1.38 0.002 (26, 27). It is important to treat insomnia symptoms because Admission for heroin detoxification 1.77 0.80–3.94 0.16 they have been identified as a risk factor for relapses after a Cluster B personality disorder 1.22 0.74–2.03 0.44 detoxification process (26). A recent study has suggested that SUD patients who have been pharmacologically treated and have improved their insomnia symptoms maintained abstinence from substance use for longer in comparison with patients who found that 84.3% of addicted patients experienced insomnia did not improve from their insomnia symptoms (35). These symptoms during active consumption of substances (28). It findings highlight the need to treat insomnia symptoms during could be hypothesized, that patients actively consuming such the therapeutic process. substances have less frequent insomnia symptoms because Other significant factors in the bivariate analysis were age, hypersomnia is an expected withdrawal symptom of the ADHD, Cluster B personality, medical comorbidities, and heroin stimulant detoxification process. addiction. All these features have been identified as risk factors The prevalence of insomnia symptoms is high, and it ranges for insomnia in previous studies (3, 4, 7). Thus, psychiatry from 59.3 to 100%, depending on the primary substance and medical comorbidities should be treated in order to used. These rates are consistent with insomnia prevalence improve insomnia symptoms and the quality of life of SUD described in other studies on SUD (17–22). Behavioral patients (36). and psychobiological factors increase the prevalence of Certain limitations of this study should be considered. insomnia symptoms in SUD patients, for example, bad First, electrophysiological tests such as polysomnography and sleep hygiene and the interaction between the hypocretinergic actigraphy were not used to assess insomnia. However, it and dopaminergic systems (13). As for the type of insomnia, has been established that these objective measures should not sleep-maintenance insomnia was observed in half of the patients take preference over clinical evaluation and clinical judgment. and was the most common type of insomnia identified. A On the other hand, it should be considered that participants similar rate has been reported in other substance-use disorder of this study were enrolled in a detoxification program patients (13). and probably they were heavier users than patients seen in In the multivariate analysis, the independent risk factors outpatient drug clinics. However, most patients with an SUD associated with insomnia symptoms were female sex, anxiety need to undergo detoxification at different stages of their disorder comorbidity, polysubstance use and prior admission addiction. It should also be noted that medications prescribed for detoxification. to patients during hospital detoxification may influence the We found that women in our study have more insomnia presence or absence of insomnia symptoms, although all the symptoms, just as they do in the general population. According patients in our study underwent a similar psychopharmacology to diverse studies and revisions, insomnia in women might approach. Unfortunately, the severity of insomnia was not be increased and affected by hormonal changes such as included in the design; however, our future studies will menstruation, pregnancy, breastfeeding, or menopause (23). include it. Another explanation is that women tend to suffer anxiety Our study also has several strengths. The fact that we used more frequently, as well as depressive disorders associated with psychometric tests to analyze a large sample of patients lends insomnia (23). In the same way, it has been found that anxiety strength to the results, providing validity to the clinical diagnosis disorders are independently associated with insomnia symptoms and the presence of insomnia symptoms. Finally, our findings in SUD patients. The relationship between insomnia and anxiety also add to the limited data on the prevalence of symptoms of disorders is unknown; however, at the neurobiological level it insomnia in patients with substance use disorders other than has been proposed that the excitability of the right parietal alcohol (12, 28). cortex in patients with generalized anxiety disorder comorbid We confirm that insomnia symptoms are very common with insomnia was modulated by insomnia (33). Moreover, the among SUD patients during detoxification, especially the subtype inclusion of insomnia symptoms among the diagnostic criteria sleep-maintenance insomnia (13). Polydrug use, comorbid of anxiety and depressive disorders increases the probability for anxiety disorder, prior admission to detoxification programs, and these comorbidities (34). being female were independent factors associated with insomnia Polysubstance use understood as a history of addiction to symptoms. A specific assessment and more psychotherapeutic three or more substances was identified as an independent risk and pharmacological strategies are needed that consider the factor for insomnia symptoms. The interaction between different symptoms of insomnia within the integral treatment of withdrawal symptoms could partially explain this association. addictions, which is a common concern among these patients Patients who had been previously admitted for detoxification and a risk factor for relapse (12, 14, 27, 28). Sleep hygiene Frontiers in Psychiatry | www.frontiersin.org 6 November 2020 | Volume 11 | Article 540022 Grau-López et al. Insomnia in Addicted Patients interventions should be included in the management of SUD AUTHOR CONTRIBUTIONS patients in order to improve their quality of life and course of addiction treatment. All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. DATA AVAILABILITY STATEMENT ACKNOWLEDGMENTS The datasets generated for this study are available on request to the corresponding author. We are grateful to the Public Health Agency of Barcelona (ASPB), the Catalan institute of Health (ICS), and the Vall ETHICS STATEMENT d’Hebron University Hospital for their support of the Hospital Detoxification Unit. We also thank Sonia Fuentes, Yasmina The studies involving human participants were reviewed and Pallares, Sira Díaz, and Nuria Tarifa from the Addiction and approved by Psychiatry Department, Vall d’ Hebron University Dual Diagnosis Unit for their collaboration in psychometric Hospital. The patients/participants provided their written assessment of the patients. We also thank Anne Murray for their informed consent to participate in this study. collaboration in reviewing English language. REFERENCES 18. Schierenbeck T, Riemann D, Berger M, Hornyak M. Effect of illicit recreational drugs upon sleep: cocaine, ecstasy and marijuana. Sleep Med Rev. (2008) 1. The International Classification of Sleep Disorders. Diagnostic and Coding 12:381–9. doi: 10.1016/j.smrv.2007.12.004 Manual. 3rd ed. Hanover: American Academy of Sleep Medicine (2014). 19. Dell’osso B, Lader M. Do benzodiazepines still deserve a major role in the 2. Buysse DJ. Insomnia. JAMA. (2013) 309:706–16. doi: 10.1001/jama.2013.193 treatment of psychiatric disorders? A critical reappraisal. Eur Psychiatry. 3. Chung KF, Yeung WF, Ho FY, Yung KP, Yu YM, Kwok CW. Cross- (2013) 28:7–20. doi: 10.1016/j.eurpsy.2011.11.003 cultural and comparative epidemiology of insomnia: the Diagnostic and 20. Irwin MR, Valladares EM, Motivala S, Thayer JF, Ehlers CL. Association statistical manual (DSM), International classification of diseases (ICD) and between nocturnal vagal tone and sleep depth, sleep quality, and International classification of sleep disorders (ICSD). Sleep Med. (2015) fatigue in alcohol dependence. Psychosom Med. (2006) 68:159–66. 16:477–82. doi: 10.1016/j.sleep.2014.10.018 doi: 10.1097/01.psy.0000195743.60952.00 4. Baglioni C, Nanovska S, Regen W, Spiegelhalder K, Feige B, Nissen C, et al. 21. Crum RM, Ford DE, Storr CL, Chan YF. Association of sleep disturbance Sleep and mental disorders: a meta-analysis of polysomnographic research. with chronicity and remission of alcohol dependence: data from a Psychol Bull. (2016) 142:969–90. doi: 10.1037/bul0000053 population-based prospective study. Alcohol Clin Exp Res. (2004) 28:1533–40. 5. Hamblin JE. Insomnia: an ignored health problem. Prim Care. (2007) 34:659– doi: 10.1097/01.ALC.0000141915.56236.40 74. doi: 10.1016/j.pop.2007.05.009 22. Brower KJ, Krentzman A, Robinson EA. Persistent insomnia, abstinence, and 6. Cunnington D, Junge MF, Fernando AT. Insomnia: prevalence, moderate drinking in alcohol-dependent individuals. Am J Addict. (2011) consequences and effective treatment. Med J Aust. (2013) 199:36–40. 20:435–40. doi: 10.1111/j.1521-0391.2011.00152.x doi: 10.5694/mja13.10718 23. Pengo MF, Won CH, Bourjeily G. Sleep in women across the life span. Chest. 7. Sutton EL. Psychiatric disorders and sleep issues. Med Clin North Am. (2014) (2018) 154:196–206. doi: 10.1016/j.chest.2018.04.005 98:1123–43. doi: 10.1016/j.mcna.2014.06.009 24. Sierra JC, Delgado-Dominguez C, Carretero-Dios H. [Internal structure of 8. Khurshid KA. Comorbid insomnia and psychiatric disorders: an update. dysfuncional beliefs and attitudes about sleep scale in a Spanish shift workers Innov Clin Neurosci. (2018) 15:28–32. sample]. Rev Neurol. (2006) 43:454–60. doi: 10.33588/rn.4308.2005733 9. Abad VC, Guilleminault C. Sleep and psychiatry. Dialogues Clin Neurosci. 25. Bain KT. Management of chronic insomnia in elderly persons. Am J Geriatr (2005) 7:291–303. Pharmacother. (2006) 4:168–92. doi: 10.1016/j.amjopharm.2006.06.006 10. Spoormaker VI, Van den Bout J. Depression and anxiety complaints; 26. Grau-López L, Roncero C, Grau-López L, Daigre C, Rodríguez-Cintas L, relations with sleep disturbances. Eur Psychiatry. (2005) 20:243–5. Pallarés Y, et al. Factors related to relapse in substance-dependent patients in doi: 10.1016/j.eurpsy.2004.11.006 hospital detoxification: the relevance of insomnia. J Sleep Disor Treat Care. 11. Cheng SH, Shih CC, Lee IH, Hou YW, Chen KC, Chen KT, et al. A study (2014) 3:3. doi: 10.1016/S0924-9338(14)78341-5 on the sleep quality of incoming university students. Psychiatry Res. (2012) 27. Brower KJ, Aldrich MS, Robinson EA, Zucker RA, Greden JF. Insomnia, self- 197:270–4. doi: 10.1016/j.psychres.2011.08.011 medication, and relapse to alcoholism. Am J Psychiatry. (2001) 158:399–404. 12. Roncero C, Grau-López L, Díaz-Morán S, Miquel L, Martínez-Luna N, Casas doi: 10.1176/appi.ajp.158.3.399 M. [Evaluation of sleep disorders in drug dependent inpatients]. Med Clin. 28. Grau-López L, Daigre C, Grau-López L, Rodriguez-Cintas L, Egido A, Casas (2012) 138:332–5. doi: 10.1016/j.medcli.2011.07.015 M, et al. Administrative prevalence of insomnia and associated clinical 13. Cañellas F, de Lecea L. [Relationships between sleep and addiction]. features in patients with addiction during active substance use. Actas Esp Adicciones. (2012) 24:287–90. doi: 10.20882/adicciones.78 Psiquiatr. (2016) 44:64–71. 14. Roth T. Does effective management of sleep disorders reduce 29. World Medical Association. World medical association declaration of substance dependence? Drugs. (2009) 69:65–75. doi: 10.2165/11531120- Helsinki. Ethical principles for medical research involving human subjects. 000000000-00000 Bull World Health Organ. (2001) 79:373–4. 15. Teplin D, Raz B, Daiter J, Varenbut M, Tyrrell M. Screening for substance use 30. Verkhratsky A, Nedergaard M, Steardo L, Li B. Editorial: sleep and mood patterns among patients referred for a variety of sleep complaints. Am J Drug disorders. Front Psychiatry. (2020) 16:981. doi: 10.3389/fpsyt.2019.00981 Alcohol Abuse. (2006) 32:111–20. doi: 10.1080/00952990500328695 31. Steardo L, de Filippis R, Carbone EA, Segura-Garcia C, Verkhratsky A, 16. Dimsdale JE, Norman D, DeJardin D, Wallace MS. The effect of opioids on De Fazio P. Sleep disturbance in bipolar disorder: neuroglia and circadian sleep architecture. J Clin Sleep Med. (2007) 3:33–6. rhythms. Front Psychiatry. (2019) 10:501. doi: 10.3389/fpsyt.2019.00501 17. Babson KA, Sottile J, Morabito D. Cannabis, cannabinoids, and 32. Faulkner S, Sidey-Gibbons C. Use of the pittsburgh sleep quality index in sleep: a review of the literature. Curr Psychiatry Rep. (2017) 19:23. people with schizophrenia spectrum disorders: a mixed methods study. Front doi: 10.1007/s11920-017-0775-9 Psychiatry. (2019) 10:284. doi: 10.3389/fpsyt.2019.00284 Frontiers in Psychiatry | www.frontiersin.org 7 November 2020 | Volume 11 | Article 540022 Grau-López et al. Insomnia in Addicted Patients 33. Huang Z, Zhan S, Chen C, Li N, Ding Y, Hou Y, et al. The quality of life among treatment-seeking patients in Spain. Qual Life Res. (2017) effect of insomnia on cortical excitability in patients with generalized 26:3201–9. doi: 10.1007/s11136-017-1668-4 anxiety disorder. Front Psychiatry. (2019) 9:755. doi: 10.3389/fpsyt.2018. 00755 Conflict of Interest: The authors declare that the research was conducted in the 34. Raffray T, Bond TL, Pelissolo A. Correlates of insomnia in absence of any commercial or financial relationships that could be construed as a patients with social phobia: role of depression and anxiety. potential conflict of interest. Psychiatry Res. (2011) 189:315–7. doi: 10.1016/j.psychres.2011. 03.004 Copyright © 2020 Grau-López, Grau-López, Daigre, Palma-Álvarez, Martínez- 35. Grau-López L, Grau-López L, Daigre C, Palma-Álvarez RF, Rodriguez-Cintas Luna, Ros-Cucurull, Ramos-Quiroga and Roncero. This is an open-access article L, Ros-Cucurull E, et al. Pharmacological treatment of insomnia symptoms distributed under the terms of the Creative Commons Attribution License (CC BY). in individuals with substance use disorders in Spain: a quasi-experimental The use, distribution or reproduction in other forums is permitted, provided the study. Subst Use Misuse. (2018) 53:1267–74. doi: 10.1080/10826084.2017. original author(s) and the copyright owner(s) are credited and that the original 1402056 publication in this journal is cited, in accordance with accepted academic practice. 36. Daigre C, Grau-López L, Rodríguez-Cintas L, Ros-Cucurull E, Sorribes- No use, distribution or reproduction is permitted which does not comply with these Puertas M, Esculies O, et al. The role of dual diagnosis in health-related terms. Frontiers in Psychiatry | www.frontiersin.org 8 November 2020 | Volume 11 | Article 540022