A 55-year-old male patient you have been treating for alcohol use disorder has been struggling with withdrawal following detox. He tells you his spouse is complaining about his severe and disruptive snoring, and he says he feels “wiped out” all day, even falling asleep at work. He then admits that, to stay alert, he has been regularly taking Adderall supplied by a colleague and now has strong cravings to have a beer to “take off the edge” after work. He is at risk for relapse, and you suspect sleep apnea might be a risk factor.

What do you do next?

Basics of sleep apnea
There are three types of sleep apnea: obstructive sleep apnea (OSA), central sleep apnea, and mixed. Of these, OSA is by far the most common, and that’s what we’ll focus on in this article.
OSA is caused by excessive relaxation of the throat during sleep, which in some people causes enough obstruction to impede the flow of air. The apnea causes them to reflexively wake up enough to temporarily open the airway, after which they fall back to sleep. Dozens or hundreds of such mini-awakenings can occur, and patients may not remember them. They may wake up thinking that they have slept all night, but they still feel exhausted.

Risk factors for OSA include obesity and enlarged tonsils (mainly a cause in children). The prevalence of diagnosed and treated OSA is around 2%–4%, but milder forms probably affect many more people. OSA’s prevalence is higher in patients with a substance use disorder (SUD). While substances can aggravate OSA, the causality often works the other way: OSA may cause fatigue and depression, which can then lead to substance use as a coping mechanism.

OSA is diagnosed through a comprehensive sleep evaluation conducted by a sleep specialist, who is commonly a pulmonologist. This involves reviewing a patient’s medications, substance use history, sleep logs, collateral history, and—crucially—polysomnography (PSG) results, the gold standard for OSA. For PSG, the patient is kept in a sleep lab overnight and physiologic variables are monitored. The main outcome measure of PSG is the apneo-hypoxia index (AHI), which is the average number of disordered breathing events per hour. Typically, OSA is defined as an AHI of 5 or greater with associated symptoms (eg, excessive daytime sleepiness, fatigue, or impaired cognition) or an AHI of 15 or greater with or without associated symptoms. Instead of PSG, home sleep testing may be used for uncomplicated adult patients (Kapur VK et al, J Clin Sleep Med 2017;13(3):479–504).

The main treatment for sleep apnea is continuous positive airway pressure (CPAP), administered via a small machine that provides low levels of air pressure through a mask to keep the airway passages open during sleep. If an individual is overweight, even a 10% reduction in weight can be beneficial. Sometimes surgical procedures are recommended to correct airway anatomy.

Stress to the patient the negative impact of substance use on sleep, as it can mask, exacerbate, or trigger OSA.

How to screen substance-using patients for OSA
Screen not just patients complaining of fatigue, but all your patients with an SUD. Start by asking, “Do you snore?” If they say no, ask if anybody else has told them that they snore. Ask, “Do you wake up feeling like your sleep is nonrestorative? Do you feel sleepy throughout the day?” Depending on your level of suspicion for OSA, ask about two other symptoms commonly seen in the disorder: morning headache and frequent nighttime urination.

If you suspect OSA, refer to a sleep specialist. Patients might ask what they should expect at a sleep evaluation, so being knowledgeable on the subject might encourage them to follow up. Say, “The specialist will take a thorough sleep history and go over all the factors in your life that might be interfering with sleep. If the specialist suspects sleep apnea, you’ll do a sleep study where you sleep in a special room while having your brain waves, breathing, and oxygen level monitored.” Also mention that the main treatment, CPAP (“a special small breathing machine”), will likely prevent serious health problems (especially cardiac ones) and give patients more years to live. In addition, CPAP has been shown to improve depressive symptoms (Economou NT, PLoS One 2018;13(6):e0197342).

Effects of substances on OSA
While screening for sleep apnea is important, the vast majority of your sleep apnea patients will have already been diagnosed by the time you see them. Sleep apnea may be one of a long list of medical problems, which in these patients commonly include hypertension, hyperlipidemia, diabetes, and other ailments associated with obesity. Add an SUD to this list, and you have a pretty complicated patient.

What’s a good approach in these cases? First, you should explain to your patient how substances can aggravate OSA.

Alcohol and benzodiazepines. Alcohol and other sedatives excessively relax the muscles of the throat, which worsens airway obstruction. In addition, sedatives impair the natural arousal reflex that allows the airway to open up for drawing the deep breaths the body needs. This is a double whammy for sleep apnea patients. Indeed, research has shown that alcohol increases the duration and frequency of apneas in OSA and increases the extent of hypoxemia. There’s even some evidence that in patients with benign chronic snoring, alcohol can actually induce OSA (Issa FG et al, J Neurol, Neurosurg, and Psychiatry 1982;45(4):353–359).

Opioids. Patients who are taking opioids, whether prescribed for chronic pain or as replacement therapy, are in a special risk category because they are vulnerable to central sleep apnea. Central sleep apnea is a relatively uncommon condition seen mostly in patients who are taking very large doses of opioids (morphine equivalent >200 mg), particularly if they are also on benzodiazepines (Correa D et al, Anesth Analg 2015;120(6):1273–1285). But even in patients taking smaller opioid doses, try to avoid using benzos.

Tobacco. Surveys have shown an association between cigarette smoking and sleep apnea, with possible mechanisms including airway inflammation and sleep instability from overnight nicotine withdrawal (Franklin KA et al, J Thorac Dis 2015;7(8):1311–1322).

Cannabis. Oddly, there is some preliminary evidence that THC can improve OSA (Carley DW et al, Sleep 2018;41(1):zsx184). Nonetheless, the American Academy of Sleep Medicine has stated that “medical cannabis and/or its synthetic extracts should not be used for the treatment of OSA due to unreliable delivery methods and insufficient evidence of effectiveness, tolerability, and safety” (Ramar K et al, J Clin Sleep Med 2018;14(4):679–681).

Thoughtful prescribing for sleep apnea patients
Your goal is to avoid meds that may worsen the condition, while selecting meds that will either improve it or will help patients tolerate CPAP treatment. (For a good review on psychiatric management of OSA patients, see: Heck T and Zolezzi M, Neuropsychiatr Dis and Treat 2015;11:2691–2698).

Antipsychotics
Try to avoid sedating antipsychotics, such as quetiapine, olanzapine, and chlorpromazine. Second-generation antipsychotics are associated with a near doubled risk of severe OSA—though the mechanism is unclear (Shirani A et al, Sleep Med 2011;12(6):591–597). So, these are not the patients who should be getting those little 25 mg doselets of Seroquel for sleep.

Antidepressants
It’s well-known that many antidepressants decrease the amount of rapid eye movement (REM) sleep. And since apneas occur more frequently during REM, decreasing REM might theoretically decrease the number of apnea episodes. However, neither tricyclics or SSRIs have been consistently shown to improve OSA. Fortunately, these meds do not worsen the condition.

Benzodiazepines
While there’s no solid evidence that benzos worsen OSA, common sense dictates they might, so you should avoid them if possible. Patients who are on benzos should limit their use to shorter-acting agents not taken too late in the day.

Non-benzodiazepines
Because non-benzos have fewer muscle relaxant effects than benzos, they are thought to be safer in OSA. Some experts actually advocate their use on the grounds that they help patients sleep while using the intrusive CPAP machines, thereby improving adherence with OSA treatment. For example, one study randomly assigned 152 OSA patients to eszopiclone (Lunesta) 3 mg or placebo for 2 weeks. Patients taking Lunesta used CPAP for more nights and for more hours per night than those taking placebo, and there were no differences in side effects between the groups (Lettieri CJ, Ann Intern Med 2009;151(10):696–702).

Stimulants
Since OSA causes daytime sedation, modafinil (Provigil) is recommended by most experts. Ideally, this should be explored only after CPAP intervention since patients who adhere to and respond well to CPAP will see resolution or improvement of daytime sedation. While stimulants also work well to treat fatigue, you should avoid them if possible because of the potential for misuse and diversion.

CATR Verdict: Make screening for OSA a part of your routine for patients with SUDs. And when prescribing meds for them, avoid psychotropics, such as sedating antipsychotics and benzodiazepines, that might worsen the condition.