Correlation Between Sleep Apnea and Methadone Therapy

https://doi.org/10.5272/jimab.2021272.3817 Journal of IMAB Journal of IMAB - Annual Proceeding (Scientific Papers). 2021 Apr-Jun;27(2) ISSN: 1312-773X https://www.journal-imab-bg.org Original article

CORRELATION BETWEEN SLEEP APNEA AND METHADONE THERAPY

Christiana Madjova1, Simeon Chokanov1, Mario Milkov2 1) Department of Conservative Dentistry and Oral Pathology, Faculty of Den- tal Medicine, Medical University – Varna 2) Department of Dental Materials Science, and Propaedeutics of Prosthetic Dental Medicine, Faculty of Dental Medicine, Medical University – Varna, Bul- garia.

SUMMARY Addiction is a brain disorder that creates mental and/ Introduction: Methadone therapy is the mainstay of or physical dependence. It tortures millions of people around treatment of addict patients. The most common side effects the world, which costs society a great deal in terms of medi- are: dizziness, drowsiness, vomiting, sweating, dry mouth and cal and social problems, and immeasurable suffering for constipation. The more serious complications that can be loved ones and for themselves [5]. Addiction is most com- observed are: sleep apnea, àbnormal heart rhythms, respira- monly observed for opioid drugs. The patients we examined tory problems, euphoria, disorientation, anxiety, seizures and were addicted to heroin. There are different modes of its ad- more. ministration: from smoking, sniffing to oral and intravenous Purpose: The purpose of this study is to determine heroin intake [5]. Drug addicts have the highest the correlation between methadone maintenance treatment psychoactive effect through intravenous administration, and sleep apnea in addict patients. which is also the most dangerous. Materials and methods: The subject of the study are Drugs are chemicals that affect a person’s physical, 81 methadone-treated drug-dependent patients, mean age 39 mental and social functions by changing them in various ± 9,07 years. Results: The answers we received: 79% (64) of drug aspects. The use and abuse of narcotic substances is com- addicts have problems with sleep; 30.9% of them (25) re- mon and increasing in recent years. This is a socially sig- ported having insomnia; 44.4% (36) experience morning fa- nificant problem worldwide [6]. tigue; 56.8% (46) of the respondents said they were drowsy Methadone therapy is the mainstay of treatment of during the day and 63% of the respondents reported a change addict patients. Methadone is a synthetic opiate has a longer in mood; 21% (17) had a short sleep, and 26% (21)reported action than heroin and acts on the same opioid receptors. snoring and 18 of them have loud bothering snoring; 68% Its euphoric effect is less pronounced. Patients take it orally answered that they don’t have problems with falling asleep to treat their addiction. If injected intravenously, it will give and only 21% don’t wake up frequently in the evening. In a heroin-like intoxication. It is essential that methadone 83.9% nobody noticed cessation of breathing during sleep. therapy is monitored by a doctor because methadone is also 73.8% never nodded off or fallen asleep while driving a ve- addictive and can have side effects. Methadone intoxication hicle. 16.1% have been treated for high blood preasure, and and abstinence are more powerful than heroin. only 2.5% have obesity. The purpose of this study is to determine the correla- Conclusions: Our survey found that there is a corre- tion between methaone maintenance treatment and sleep lation between methadone therapy and sleep of patients. The apnea in addict patients. key to improving the condition and reducing the risk of central sleep apnea is the monitoring of patients, as well as a MATERIALS AND METHODS combination of different types of treatment. Our survey was conducted among 81 drug addicted patients treated with methadone, 58 men (72%) and 23 Keywords: Methadone, Opiate dependence, Drug ad- women (28%). Prior to the survey, they signed informed con- dicts, Sleep apnea, Central sleep apnea, Sleep disorders, sent and completed an anonymous survey. Most of them were treated at University Hospital “St. Marina” – Varna in the INTRODUCTION Department of Psychiatry and Medical Psychology and were Methadone is an opioid used to treat chronic pain as monitored outpatientin the Diagnostic Consultative Center well as supportive therapy in opioid-dependent patients. Its “St. Marina”– Varna, where we conducted the survey. most common side effects are: dizziness, drowsiness, vomit- Patients met several including criteria: to be on ing, sweating, dry mouth and constipation. [1, 2]. The more methadone therapy for at least 2 months, to be addicted to serious complications that can be observed are: sleep apnea, opioid drugs, to complete informed consent. àbnormal heart rhythms, respiratory problems, euphoria, All participants filled an anonymous survey in order disorientation, anxiety, seizures and more [2, 3, 4]. for their sleep problems to be clarified in details. The study

J of IMAB. 2021 Apr-Jun;27(2) https://www.journal-imab-bg.org 3817 consisted of 14questions for sleep assessment. The issues of • “Has anyone noticed that you quit breathing dur- the survey refer to problems with sleep, mood swings, snoring your sleep?”- Nearly every day (0 pts); 3–4 times a week ing and quality of sleep.We used the scientific literature to (2 pts, 2.5%); 1–2 times a week(3 pts, 3.7%); 1–2 times a compare our data from a polysomnographic study for sleep month(8 pts, 9.9%); Never or nearly never(68 pts, 83.9%) apnea in methadone therapy. • On the question “Have you ever nodded off or fallen asleep while driving a vehicle?”- 1 patient (1.2%) answered RESULTS “nearly every day”; 3 patients (3.7%) - 3–4 times a week; 5 The 81 patients we examined were 39 ± 9,07 years of patients (6.2%) - 1–2 times a week; 1–2 times a month (13 age (mean ± SD). The proportion between men and women pts, 16.1%); and “never or nearly never” -59 pts (72.8%) was unequal. Themen are twice as many as women (58 ver- • Do you have or are you being treated for high blood sus 23). Their distribution as a percentage is given in Fig- pressure? – 13 patients (16.1%) have ure 1. • BMI ≥35 kg/m2? – only 2 patients (2.5%) answered All of them are drug addicts, treated at the Univer- positively sity Hospital “Saint Marina” and monitored at Diagnostic Consultative Center “Saint Marina”– Varna, where we con- Fig. 2. The share of pts with the sleep problem ducted the polysomnographic study and the survey.

Fig. 1. Percentage of examined patients

Fig. 3. The share of pts with insomnia

We prepared a special questionnaire for patients. Af- ter they filled it, we summarized the received answers by calculating the percentage of answers with “Yes” or “No”, respectively, and the results are shown in Figures 2 to 11, 14 and 15. Two of the questions had multiple choice, they are shown in Figures 12 and 13. The first question was about sleeping problems - whether or not patients had them. We found that 79% said they had (fig.2). Each patient reported a different sleep problem. On the following questions, the received answers are shown as a percentage: • “Do you suffer from insomnia?” 25 (30,9%) re- sponded positively • “Do you have morning fatigue?” - 44.4% (36) said they experience morning fatigue Fig. 4. The share of pts with morning fatigue • “Do you feel sleepy during the day?” 56,8% (46) answered negatively • 63% of patients reported “mood swings during the day” • To the questions “Is your dream short?” and “Do you snore?” patients who answered “yes” were respectively 21% (17) and 26% (21) • From patients who answered yes on previous question (21pts), 18 answered that their snoring bothered other people • 26 (32%) patients had difficulty falling asleep. • 21% (17) of the respondents do not wake up often in the evening

3818 https://www.journal-imab-bg.org J of IMAB. 2021 Apr-Jun;27(2) Fig. 5. The share of pts feeling sleepy during the day Fig. 9. The share of pts whossnoring bother others

Fig. 6. The share of pts with mood swing Fig. 10. The share of pts who hard falling asleep

Fig. 7. The share of pts with a short dream Fig. 11. The share of pts who often wake up

Fig. 8. The share of pts with snoring

J of IMAB. 2021 Apr-Jun;27(2) https://www.journal-imab-bg.org 3819 Fig. 12. The share of pts whos partner noticed cessation of breathing

Fig. 13. The share of pts whoever nodded off or fallen asleep while driving a vehicle

Fig. 14. The share of pts who are /have been treated Fig. 15. The share of pts with BMI ≥35kg/m2 for high blood pressure

DISCUSSION The relationship between drugs use and sleep is two- way. On the one hand, opioid use causes sleep disorders, and on the other, sleep problems affect recurrent opiate abuse [7]. Central sleep apnea (CSA) is characterized by a lack of airflow for ≥10 seconds with no effort of breathing, and

3820 https://www.journal-imab-bg.org J of IMAB. 2021 Apr-Jun;27(2) an apnea-hypopnea index (AHI)of more than 5 per hour is ble with sleep and wake up. These short, breath-taking considered significant [8]. awakenings are typical of central sleep apnea. Mood For the diagnosis of central sleep apnea in opioid- changes are also one of the symptoms of apnea, but they dependent patients, there are 3 clinical symptoms that may overlap with patients’ mental state, and addiction treatment be present both individually and together: 1) the respira- has many effects on them. tory pattern - ataxia or irregularly; 2) interruption of breath- We observed other typical symptoms we observed ing - apnea or hypopnea 3) gas exchange - hypoxia and in our patients have increased daytime sleepiness in 56.8% hypercapnia. Central apnea may have different morphol- and morning fatigue in 44.4%.Many of these patients have ogy: irregular intervals with ataxic respiration or periodic insomnia (30,9%). A smaller percentage of those surveyed with cluster respiration [8]. were found to have short sleep and snore. Polysomnographic examination is the gold standard What the partner of the respondents thinks is ex- for diagnosing OSA, but it is a time-consuming and costly tremely important for conducting this survey. Some of the procedure. To address this problem, many studies use de- questions focused on what others were saying about the veloped screening questionnaires to help identify patients sleeper. In 83.9% of drug addicts, their partners did not no- with OSA.The survey method is a proven useful, simple and tice the symptom of sleep apnea - cessation of breathing. alternative approach used to diagnose sleep apnea by ask- It is crucial that 27.2% percentage of patients nod- ing patients to report their symptoms[9,10]. Our question- ded off or fell asleep while driving. This may be due to naire is a self-administered screening tool, which combines both fatigues from sleep apnea and opiates taken by the questions about the risk factors for sleep apnea. In this way, subjects. It is very difficult to distinguish the cause of this the risk can be determined. problem. Breathing disorders during sleep (sleep disordered Other risk factors for sleep apnea are obesity and breathing) in patients using opiates are extremely high. Ac- high blood pressure. In this study, we did not find it to af- cording to the study of Correa D et al., they range from 42% fect drug addicts. A very small percentage of those surveyed to 85%, and the incidence of central sleep apnea is many had BMI ≥35. times higher than in the general population (24%) [8]. How to manage sleep apnea in methadone treated After taking opioids, breathing becomes shallow and addicted? irregular, leading to hypercapnia and hypoxia. The specific Guilleminault C. (2010) showed the most accurate one observed by Randerath WJ and George S (2012) in diagnosis of central sleep apnea is a combination of opioid-induced sleep apnea patients is daytime drowsiness, polysomnographic study and discussions with a multidis- dizziness, and impaired concentration [11]. ciplinary team. He has observed 2 abnormal breathing pat- For the most accurate diagnosis of central sleep terns in the diagnosed patients - reduced effort to inhale apnea, a polysomnographic study should be used as well during an obstructive event and longer than expected res- as a multidisciplinary team. Two abnormal breathing pat- piration pauses [14]. terns are observed in diagnosed patients - reduced effort Treating patients with sleep apnea as a result of to inhale during an obstructive event and longer than ex- opioids is extremely challenging. There are different study pected respiration pauses [14]. In a polysomnographic and opinions. According to Correa D. and Farney R. (2015), study done by Sharkey, K, and a team of 71 methadone pa- constant positive pressure apparatus is most commonly used tients, 42.2% of participants had at least one form of SDB for treatment, and different types of oxygen devices are [15]. Correa D. and Farney R. observed central sleep apnea used. Some patients may require a reduction in the opiate (CSA) in a study of patients receiving methadone therapy dose or the choice of another drug with less methadone tox- [8]. With this type of sleep apnea, patients stop breathing icity (such as buprenorphine), as well as drug treatment or breathing is very low, and they cannot supply oxygen. with acetazolamide, theophylline and carbon dioxide [8]. It presents a more serious treatment challenge. Troitino A. et al. (2014) made a study in patients with The major risk of methadone use is death from respira- sleep disorders, and his conclusion is that patients with cen- tory depression, especially when initiating therapy or chang- tral sleep apnea due to opiates are not significantly affected ing doses [12]. Many studies have shown that methadone by CPAP (Continuous positive airway pressure therapy) therapy leads to an increase in the incidence of sleep apnea treatment. Only 24% of addicted showed improvement com- symptoms, and the quality of sleep in these patients is very poor. pared with the control group with idiopathic central sleep This reflects on the quality of life of patients [13]. apnea (38%) [16]. The data we obtained showed that addicts receiving Guilleminault and the team also observe the same, methadone patients have trouble sleeping. The explanation but they report differences in obese patients and those with of this in the literature is that unlike obstructive sleep lower BMI. In their view, those with lower body weight apnea, in which the muscles of the throat are relaxed, in have a different breathing pattern, which respond well to central sleep apnea (more common in opioids use), the CPAP therapy [14]. brain does not send the correct signals to the muscles that Oxygen therapy corrects hypoxemia but does not af- control breathing. fect patients’ ataxic breathing. Patients may experience We found that 79% of patients reported sleep prob- potentiation of hypoventilation or prolongation of central lems. Different symptoms vary within various limits. Pa- apnea/hypopnea. But oxygen therapy rarely causes respi- tients stop breathing for a certain period of time, have trou- ratory depression, as opioids stabilize respiration if the

J of IMAB. 2021 Apr-Jun;27(2) https://www.journal-imab-bg.org 3821 arousal threshold is low and the respiratory controller gain spite the high prevalence of sleep problems in drug ad- is high, associated with pain. Oxygen is added in addition dicts, this therapy is necessary and should be closely to CPAP treatment for optimal treatment [8]. monitored by their psychiatrists. The key to improving the condition and reducing the risk of central sleep apnea CONCLUSION: is in monitoring patients, as well as a combination of dif- We found in our study that there is a correlation ferent types of treatment. between methadone therapy and the sleep of patients. De-

REFERENCES: 1. Martin WR, Jasinski DR, Maintenance Treatment Volunteers and Breathing, and the Endocrine System. Haertzen CA, Kay DC, Jones BE, Opium-dependent Patients. Addict In: Handbook of Methadone Prescrib- Mansky PA, et al. Methadone—a Health. 2016 Apr;8(2):84-89. [PubMed] ing and Buprenorphine Therapy. Edi- reevaluation. Arch Gen Psychiatry. 8. Correa D, Farney RJ, Chung F, tors Cruciani R, Knotkova H. Springer, 1973 Feb;28(2):286-95. [PubMed] Prasad A, Lam D, Wong J. Chronic New York, NY. 2013. pp.39-49. 2. Nicholson AB, Watson GR, Derry opioid use and central sleep apnea: a [Crossref] S, Wiffen PJ. Methadone for cancer review of the prevalence, mechanisms, 13. Charpentier A, Bisac S, Poirot I, pain. Cochrane Database Syst Rev. and perioperative considerations. Vignau J, Cottencin O. Sleep quality 2017 Feb 8;2(2):CD003971. [PubMed] Anesth Analg. 2015 Jun;120(6):1273- and apnea in stable methadone main- 3. John J, Amley X, Bombino G, 85. [PubMed] tenance treatment. Subst Use Misuse. Gitelis C, Topi B, Hollander G, et al. 9. Chung F, Yegneswaran B, Liao P, 2010 Jul;45(9):1431-4. [PubMed] Torsade de Pointes due to Methadone Chung SA, Vairavanathan S, Islam S, 14.Guilleminault C, Cao M, Yue Use in a Patient with HIV and Hepati- Khajehdehi A, Shapiro CM. STOP ques- HJ, Chawla P. Obstructive sleep apnea tis C Coinfection. Cardiol Res Pract. tionnaire: a tool to screen patients for and chronic opioid use. Lung. 2010 2010 Dec 30;2010:524764. [PubMed] obstructive sleep apnea. Anesthe- Dec;188(6):459-68. [PubMed] 4. Sinha S. Methadone. Drugs.com. siology. 2008 May;108(5):812-21 15. Sharkey KM, Kurth ME, Nov. 2019 [Internet] 10. Abrishami A, Khajehdehi A, Anderson BJ, Corso RP, Millman RP, 5. Koob G, Arends M, Le Moal M. Chung F. A systematic review of screen- Stein MD. Obstructive sleep apnea is Drugs, Addiction, and the Brain. 1st ing questionnaires for obstructive sleep more common than central sleep apnea Edition. Academic Press, Elsevier. apnea. Can J Anesth/J Can Anesth in methadone maintenance patients 2014. Chapter 1: vii. [Internet] (2010) 57:423–438 with subjective sleep complaints. Drug 6. Fudin HR, Babin JL, Hong JT, Ku 11. Randerath WJ, George S. and Alcohol Dependence, 2010; J, May AL, Wisner A, et al. Drugs of Opioid-induced sleep apnea: is it a real 108(1-2), 77–83 Abuse. Side Effects of Drugs Annual. problem? J Clin Sleep Med. 2012 Oct 16. Troitino A, Labedi N, Kufel T, Volume 40, 2018. Chapter 4. pp.29-89 15;8(5):577-8. [PubMed] El-Solh AA. Positive airway pressure [Crossref] 12. Webster LR. Methadone Side therapy in patients with opioid-related 7. Khazaie H, Najafi F, Ghadami Effects: Constipation, Respiratory De- central sleep apnea. Sleep Breath. 2014 MR, AzamiA, Nasouri M, Tahmasian pression, Sedation, Sleep-Disordered May;18(2):367-73. [PubMed] M, et al. Sleep Disorders in Methadone

Please cite this article as: Madjova C, Chokanov S, Milkov M. Correlation between sleep apnea and methadone therapy. J of IMAB. 2021 Apr-Jun;27(2):3817-3822. DOI: https://doi.org/10.5272/jimab.2021272.3817

Received: 24/06/2020; Published online: 28/06/2021

Address for correspondence: Christiana Madjova Department of Conservative Dentistry and oral pathology, Faculty of Dental Medicine, Medical University – Varna. 84, TzarOsvoboditel Blvd., 9000 Varna, Bulgaria E-mail: [email protected], 3822 https://www.journal-imab-bg.org J of IMAB. 2021 Apr-Jun;27(2)