Obstructive sleep apnea may be one reason depression treatment doesn't work

July 23, 2019

Science Daily/Medical College of Georgia at Augusta University

When someone is depressed and having suicidal thoughts or their depression treatment just isn't working, their caregivers might want to check to see if they have obstructive sleep apnea, investigators say.

That's true even when these individuals don't seem to fit the usual profile of obstructive sleep apnea, which includes males who are overweight, snore and complain of daytime sleepiness, says Dr. W. Vaughn McCall, chair of the Department of Psychiatry and Health Behavior at the Medical College of Georgia at Augusta University.

"No one is talking about evaluating for obstructive sleep apnea as a potential cause of treatment-resistant depression, which occurs in about 50 percent of patients with major depressive disorder," says McCall, corresponding author of the study in The Journal of Psychiatric Research. Now he hopes they will.

The investigators found clinically relevant disease in 14 percent of 125 adult patients with major depressive disorder, insomnia and suicidal thoughts, even though the sleep-wrecking apnea was an exclusion criterion for the original study.

While more work remains, McCall reasons that the new evidence already suggests that testing for obstructive sleep apnea should be part of the guidelines for managing treatment resistant depression.

"We were completely caught by surprise that people did not fit the picture of what obstructive sleep apnea is supposed to look like," says McCall.

While it's known that people with obstructive sleep apnea have higher rates of depression than other populations, little is known about rates of obstructive sleep apnea in patients with major depressive disorder, so investigators decided to look in a population of patients they already were studying.

The primary intent of the original study was looking at whether treating patients' insomnia in addition to their depression reduced suicidal thoughts. Patients considered at risk for obstructive sleep apnea were excluded since sleeping pills tend to relax muscle and already-too relaxed throat muscles is a primary problem in obstructive sleep apnea. Also excluded were individuals with restless leg syndrome, which is common with sleep apnea even in patients on therapy, and those with morbid obesity, considered a major risk for obstructive sleep apnea.

But when the 125 people enrolled were actually tested with a sleep study at home or in a sleep center, investigators still found disease in 17.

The investigators note that neither the degree of daytime sleepiness nor insomnia accurately predicted the severity of obstructive sleep apnea they identified in these patients and that six of the 17 individuals diagnosed were female, not obese and reporting insomnia rather than classic daytime sleepiness.

Treatment of obstructive sleep apnea may improve symptoms of depression, and comprehensive screening for the sleep problem should be included for treatment resistant depression, write the team of investigators that also includes researchers from the University of California, Irvine; the University of Wisconsin in Madison; Wake Forest School of Medicine in Winston-Salem, North Carolina; and the University of California, San Francisco

It's acknowledged that undetected medical or psychiatric conditions can be a cause of treatment-resistant depression, but obstructive sleep apnea is not on the relatively long list that includes endocrine disorders, like hypothyroidism, as well as problems like coronary artery disease and cancer.

In the quest to find a reason for a lack of response, patients may get an MRI scan, carotid artery studies even a spinal tap.

"I am thinking before we do a spinal tap for treatment-resistant depression, we might need to do a sleep test first," says McCall. He notes that even other depression treatment options, like transcranial magnetic stimulation, which uses rapid magnetic pulses to change brain activity, while noninvasive are still far more costly than a sleep study.

"We know that patients with sleep apnea talk about depression symptoms," McCall says. "We know that if you have obstructive sleep apnea, you are not going to respond well to an antidepressant. We know that if you have sleep apnea and get CPAP, it gets better and now we know that there are hidden cases of sleep apnea in people who are depressed and suicidal."

Forty-four percent of the 125 patients in this study had treatment-resistant depression and four of the 17 diagnosed with obstructive sleep apnea had severe problems. Most with obstructive sleep apnea were in the upper end of the age range of 18 to 65 -- sleep apnea and other sleep problems tend to increase with age -- and were similar in other respects like sex and weight.

Ten years ago in a study of 73 outpatients with depression and insomnia but considered at low risk for sleep apnea, McCall identified 8.2 percent actually had moderate sleep apnea. A subsequent larger study by another group found 14 percent of 703 adults with depression also had obstructive sleep apnea, and others have reported similar findings. This appears to be the first study in which suicidality also was a factor.

Important remaining questions include whether when suicide is also a factor, does treating sleep apnea also reduce suicidal thoughts, says McCall, an expert in the trifecta of depression, insomnia and suicide.

McCall and others have shown that if you don't sleep you get depressed and depression is a major risk for suicide. In fact, McCall reported several years back that when people lose hope of ever getting another good night's sleep, they are at high risk for suicide.

Sleep apnea tends to produce excessive daytime sleepiness but this study was recruiting for patients with insomnia, and most with insomnia don't have sleep apnea, rather issues like anxiety, stress and depression and other emotional and psychological factors are more likely interfering with their sleep. Rather than complain of daytime sleepiness, females are more likely to say they are unable to fall asleep and stay asleep at night and are more likely to be depressed, McCall says.

Treatment-resistant depression also can result as a side effect of other medications, including commonly prescribed drugs like beta blockers and corticosteroids for problems like lupus and rheumatoid arthritis.

"The fact is depression treatment often does not work very well," says McCall. In fact, evidence has shown that patients who do not respond to one antidepressant are actually progressively less likely to respond to subsequent drugs that are tried. "It's the law of diminishing returns," McCall says.

https://www.sciencedaily.com/releases/2019/07/190723104041.htm

Silent epidemic? Head injury may be linked to lasting sleep problems

April 27, 2016

Science Daily/American Academy of Neurology

People who have had a traumatic brain injury may still have sleep problems a year and a half after being injured, according to a study. In addition, people with TBI may also be unaware of just how much their sleep is disturbed.

Every year in the United States, 1.7 million people experience a TBI and there is evidence that the rate of TBI is rising worldwide.

"This is the longest prospective and most comprehensive study about sleep quality and TBI to date," said study author Lukas Imbach, MD, of the University Hospital Zurich in Zurich, Switzerland. "We found that the majority of those with TBI, no matter how severe, had long-term sleep disturbances, yet didn't know."

For the study, researchers followed 31 people who had experienced a first TBI for 18 months. The injuries ranged from mild to severe. People with TBI were then compared to a control group of 42 healthy people.

Study participants were asked to report their own sleep behavior and daytime sleepiness. They were also monitored for two weeks with a device worn on the wrist that measures body movement. They also spent a night in a sleep video lab, which measures brain activity, eye movements, muscle activity and heart rhythm. They also took a test for excessive daytime sleepiness, which measures how quickly people fall asleep in a quiet environment during the day.

Researchers found that 67 percent of those with TBI suffered from excessive daytime sleepiness compared to just 19 percent of healthy people. In addition, when they were asked how sleepy they were during the day, those with TBI didn't report feeling any sleepier than those without TBI.

"Excessive daytime sleepiness is associated with public safety hazards such as car accidents, so people with TBI and their doctors should be monitoring for this problem," Imbach said. "The study also shows us that people with TBI may not be able to accurately assess their own sleep problems. Since this is how the sleep quality of many people with TBI is assessed, this may be a concern."

People with mild TBI were just as likely to have sleep problems as people with severe TBI, and the researchers did not find any other health problems that could have contributed to the sleep problems.

Researchers found that those with TBI slept longer, an average of eight hours a night, compared with healthy people who slept an average of seven hours a night.

"This study makes a compelling case that sleep-wake disorders after TBI may represent a silent epidemic," said Imbach. "It raises the question as to whether people with TBI should be referred for sleep studies. But further study is needed before any new recommendations are made or any guidelines are changed."

https://www.sciencedaily.com/releases/2016/04/160427221158.htm

Weight Gain Induced by High-Fat Diet Increases Active-Period Sleep

July 10, 2012

Science Daily/Society for the Study of Ingestive Behavior

Research presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB) finds that prolonged exposure to a high-fat diet reduces the quality of sleep in rats.

Using radio-telemetry, the authors measured 24-hour sleep and wake states after rats consumed a high fat diet for 8 weeks. Compared to rats that consumed a standard laboratory chow, the rats on the high-fat diet slept more but sleep was fragmented. The increased sleep time of the rats on the high-fat diet occurred mainly during the normally active phase of the day, resembling excessive daytime sleepiness observed in obese humans.

According to lead author, Catherine Kotz, "Studies in humans indicate a relationship between sleep quality and obesity. Our previous work in animals shows a link between good quality sleep, resistance to weight gain and increased sensitivity to orexin, a brain chemical important in stabilizing sleep and wake states. The current studies show that after high-fat diet-induced weight gain in rats, sleep quality is poor and orexin sensitivity is decreased. These findings suggest that poor sleep associated with weight gain due to a high-fat diet may be a consequence of reduced orexin sensitivity."

These studies highlight the impact of weight gain on sleep quality and a potential brain mechanism underlying these diet and weight-gain induced changes in sleep behavior.

http://www.sciencedaily.com/releases/2012/07/120710093804.htm

Insomnia May Perpetuate Depression in Some Elderly Patients

April 4, 2008

Science Daily/American Academy of Sleep Medicine

In addition to being a risk factor for a depressive episode, persistent insomnia may perpetuate the illness in some elderly patients, and especially in those receiving standard care for depression in primary care settings, according to a new study.

According to the results, patients with persistent insomnia were 1.8 to 3.5 times more likely to remain depressed, compared with patients with no insomnia. The findings were more robust in patients receiving usual care for depression than in patients receiving enhanced care. The findings were also stronger in subjects who had major depressive disorder as opposed to those with dysthymia alone.

"Even when depression was identified and treated in the primary care setting, the older adults in this study were more likely to remain depressed if they also exhibited persistent insomnia.

The finding that this risk was higher in the usual-care group suggests that enhanced depression care may partially mitigate the perpetuating effects of insomnia on depression," said Dr. Pigeon.

"While the findings make intuitive sense, until relatively recently insomnia was often considered a symptom that dissipated without active intervention once a primary condition like depression was treated, instead of being considered a distinct clinical entity that might affect a primary disorder. This study has several limitations, not the least of which are that it is not a causal study nor does it unequivocally answer the question of whether insomnia that presents with depression is a symptom or a co-morbid disorder. What seems most likely is that insomnia is indeed simply a symptom in some cases, but clearly a disorder requiring its own treatment focus in other cases."

Not sleeping well can lead to a number of problems. Older adults who have poor nighttime sleep are more likely to have a depressed mood, attention and memory problems, excessive daytime sleepiness, more nighttime falls and use more over-the-counter or prescription sleep aids. In addition, recent studies associate lack of sleep with serious health problems such as an increased risk of obesity, cardiovascular disease and diabetes.

http://www.sciencedaily.com/releases/2008/04/080401081930.htm

Lead exposure impacts children's sleep

Novel finding shows that lead exposure in early childhood increase risk for sleep problems, excessive daytime sleepiness

November 12, 2015

Science Daily/University of Pennsylvania School of Nursing

Lead exposure in early childhood are associated with increased risk for sleep problems and excessive daytime sleepiness in later childhood, new research shows. This is the first longitudinal, population-based study that investigated early lead exposure to sleep problems.

The research is based on data from a longitudinal, cohort study -- involving more than 1400 Chinese children -- that began in 2004 investigating the influence of lead exposure in relation to the development of children and adolescents' neurocognitive, behavioral and health outcomes. Lead pollution is pervasive throughout China and other developing countries, and though rates of lead exposure are decreasing due to the phase-out of leaded gasoline and increased public awareness, its persistence presents a significant health risk to children.

"Little is known about the impact of heavy metals exposure on children's sleep, but the study's findings highlight that environmental toxins -- such as lead -- are important pediatric risk factors for sleep disturbance," said the study's principal investigator Jianghong Liu, PhD, FAAN, Associate Professor at Penn Nursing and a faculty member at Penn's Perelman School of Medicine. "Lead exposure is preventable and treatable, but if left unchecked can result in irreversible neurological damage."

This is an important advancement in identifying and understanding the contribution of lead exposure to childhood insomnia and daytime sleepiness. Sleep problems are highly prevalent in children and adolescents and are associated with many adverse health outcomes including developmental disorders and intellectual and neurocognitive problems.

"This study addresses an important but often neglected area of sleep science, namely, environmental factors that disrupt sleep biology and behavior in children and other vulnerable populations," said the study's senior author David Dinges, PhD, Professor and Chief of the Division of Sleep & Chronobiology in the Department of Psychiatry at Penn Medicine.

The sleep problems reported by the adolescents in the study include excessive daytime sleepiness, insomnia, early morning awakening, trouble initiating and maintaining sleep, and having to use sleeping pills, all of which highlight poor sleep quality. Using the data from the cohort study, 665 children's blood lead levels were assessed when they were between three and five years old, and sleep was assessed six years later, when the children were between nine and eleven years old. The children and their parents answered separate questionnaires about the children's daily sleep patterns, insomnia and the use of sleeping pills.

Child-reported insomnia and use of sleeping pills were two times and three times more prevalent in children with blood lead levels (BLL) greater than or equal to 10 ug/dL than in children with BLL less than 10 ug/dL. This suggests that sleep disturbances appeared problematic enough for children to suffer from insomnia and even to use sleeping aids/pills in an attempt to ameliorate their symptoms.

"Insufficient sleep and daytime sleepiness is very prevalent in children and adolescents, and it is a pervasive problem that is linked with a significant public health burden," explained Liu. "More research needs to be done to identify contributing factors and ways to prevent or reduce their impact. Doing this can not only help alleviate sleep disturbance, but can also indirectly improve sleep-related health outcomes, including cognition, emotion, behavior, and in some cases, diabetes."

http://www.sciencedaily.com/releases/2015/11/151112161427.htm