DEPRESSION AND SLEEP APNEA: RESEARCH SHOWS SLEEP APNEA TREATMENT MAY RESOLVE RESIDUAL DEPRESSIVE SYMPTOMS. CPAP and Oral Appliances are indicated

A new study "Effect of CPAP treatment on residual depressive symptoms in patients with major depression and coexisting sleep apnea: Contribution of daytime sleepiness to residual depressive symptoms." (see abstract below) suggests that treatment of sleep apnea will aid in resolution of symptoms. While this study used CPAP, Oral Appliances should have identical results.

The study concludes that "The results suggest that MDD patients with residual depressive symptoms despite pharmacotherapy who also have symptoms of suspected OSA, such as loud snoring, obesity, and daytime sleepiness, should be evaluated for sleep apnea by polysomnography and treated with an appropriate treatment such as CPAP. CPAP treatment may result in a significant improvement of residual depressive symptoms due to the improvement of daytime sleepiness in these patients.

Another study "Obstructive sleep apnea and depression." (see abstract below) reports 21-41% depression in sleep pne patients. It sites a previous study that lists sleep apnea as a risk factor for depression. It is not surprising that " Patients who have depression as well as OSA appear worse off than those with OSA only" ties together symptoms and treatments of sleep apnea, headaches and depression.

An opinion statement in Curr Treat Options Neurol. 2010 Jan;12(1):1-15 on on "SLEEP AND HEADACHES" ties together headaches, psychiatric problems and sleep apnea but stops short of what the NHLBI report that focuses on masticatory/trigeminal orgin of these problems.

The NHLBI published a report on the "CARDIOVASCULAR AND SLEEP RELATED CONSEQUENCES OF TEMPOROMANDIBULAR DISORDERS" THAT LOOKS AT MASTICATORY SYSTEM AS A COMMON CAUSE OF SLEEP APNEA, HEADACHES AND MANY OTHER PROBLEMS. Shimshak et al published two articles in Cranio that showed a 200-300% increase in medical costs in every field of medicine in patients diagnosed with TMJ disorders. This would include headache, migraine, depression and other diverse conditions.

The National Heart Lung and Blood Institue report states:
"The term TMD refers to a collection of medical and dental conditions affecting the temporomandibular joint (TMJ) and/or muscles of mastication, as well as contiguous tissue components. Symptoms range from occasional discomfort to debilitating pain and severely compromised jaw function. The masticatory apparatus is not only involved in chewing and swallowing but also in other critical tasks, including breathing and talking. Specific etiologies such as trauma and degenerative arthritides underlie some forms of TMD but there is no common etiology or biological explanation. TMD is hence comprised of a heterogeneous group of health problems whose signs and symptoms are overlapping but not identical.
Although broad longitudinal and cross-sectional epidemiological studies have not been carried out, TMD is estimated to affect about 12% of the general population, representing more than 34 million Americans. The majority of those seeking treatment are women in their reproductive years. As for many other pain conditions, the clinical scenario of TMD also tends to be more severe in women than men. TM disorders are considered a serious health problem because many individuals lose their ability to hold regular jobs and to function productively even within the context of a household environment.

The report talks about symptoms including "TMD has been used to characterize a wide range of conditions diversely presented as pain in the face or jaw joint area, masticatory muscle pain, headaches, earaches, dizziness, limited mouth opening due to soft or hard tissue obstruction, TMJ clicking or popping sounds, excessive tooth wear and other complaints."

The report also discusses effects on swallowing and breating ease: "There appears to an associated increase in coughing in subjects with sleep apnea. Occlusion of the pharynx can force residual secretions into the glottis and trigger coughing reflexes, swallowing reflexes, and other reflexes that could contribute to the disorganization of breathing during sleep. In addition to the muscles of mastication, the tongue plays an important role in the coordinated events of swallowing and breathing. The integration of breathing and swallowing is tightly linked, and these events in turn are in some manner linked to blood pressure regulation. Each of these pathways has been studied by scientists in individual disciplines, but there is a need for interdisciplinary studies to determine the interactions of the peripheral and central neural pathways controlling breathing, chewing, swallowing, and cardiovascular events. The presence of pain in patients with TMD would be expected to seriously impact upon these reflex and motor pathways. Little is known about the role of tongue position and how this may be altered in subjects with altered jaw location and structure. Sleep state has been shown to alter the central modulation of the coordination of breathing, airway dynamics, swallowing, and associated cardiovascular events. Differences in central modulation of these events in subjects with sleep apnea and TMD need to be evaluated using sleep as a dynamic change in the state of the individual. Cardiovascular, neuroendocrine, respiratory and swallowing alterations in awake and sleeping subjects need to be studied in a systematic manner in both in animal models and human subjects."

There are common developmental aspects that have been well documented between sleep apnea and TMJ disorders. There is an enormous cross over of signs and symptoms as well. While all sleep apnea may not be entirely related to masticatory structures there is unquestionably a large amount of crossover. There is a solid base of evidence based studies showing how airway issues change growth and development. There is also solid evidence based studies on treatment of sleep apnea with appliances that anteriorly position the mandible. there are numerous clinical reports and studies showing treatment of headaches and TMJ disorders with anterior positiong.

Is it time to look at a large proportion of sleep apnea as being related to jaw development. This would make it a treatment that could be treated and corrected by early interventions such as tonsilectomy and maxillary expansion. Maxillary expansion allows the mandible to automatically anteriorly position and frequently grow a healthier airway. A recent study showed that most pediatric patients having tonsils removed should also have expansion. Expansion according to many experts should precede tonsilectomy to reduce post operative risks.

The early correction of airway and jaw disorders could possibly save massive dollars in lifetime medical expenses if we extrapolate from the work of Shimshak. Shimshak did not show a correlation not cause and effect of TMJ disorders to increased medical expenses.

My opinion is that there is a definite cause and effect of TMJ disorders to massive increases in medical expenses. I believe that for the majority of patients sleep apnea are due to masticatory conditions that should be defined as a TMJ disorder. If we define sleep apnea as a TMJ disorder that other problems like ADD and ADHD are secondary TMJ disorders. This would also apply to morning headaches, cardiovascular, neurological, and psychiatric disorders


Sleep Med. 2010 Jun;11(6):552-7. Epub 2010 May 21.
Effect of CPAP treatment on residual depressive symptoms in patients with major depression and coexisting sleep apnea: Contribution of daytime sleepiness to residual depressive symptoms.
Habukawa M, Uchimura N, Kakuma T, Yamamoto K, Ogi K, Hiejima H, Tomimatsu K, Matsuyama S.

Department of Neuropsychiatry, Kurume University School of Medicine, Kurume, Fukuoka, Japan. hmitsu@med.kurume-u.ac.jp
Abstract
BACKGROUND: Although extensive studies have indicated a relationship between obstructive sleep apnea (OSA) and depressive symptoms, the effect of continuous positive airway pressure (CPAP) treatment on residual depressive symptoms in patients with both major depressive disorder (MDD) and coexisting OSA has not been examined.

METHODS: Seventeen patients with continued MDD despite pharmacotherapy such as antidepressants and/or benzodiazepines, who also had comorbid OSA, were required to complete the Beck Depression Inventory (BDI), Hamilton Rating Scale for Depression (HRSD), and Epworth sleepiness scale (ESS) at the commencement of the study and then again after 2 months of CPAP treatment.

RESULTS: BDI and HRSD scores decreased from 19.7 to 10.8 and 16.7 to 8.0 after 2 months of CPAP treatment (both p<0.01). We also found significant correlations among the improvement rates in BDI, HRSD and ESS scores (R=0.86 and 0.75, both p<0.01). The mixed effect model demonstrated a significant ESS effect on BDI and HRSD.

CONCLUSIONS: The results suggest that MDD patients with residual depressive symptoms despite pharmacotherapy who also have symptoms of suspected OSA, such as loud snoring, obesity, and daytime sleepiness, should be evaluated for sleep apnea by polysomnography and treated with an appropriate treatment such as CPAP. CPAP treatment may result in a significant improvement of residual depressive symptoms due to the improvement of daytime sleepiness in these patients.

PMID: 20488748 [PubMed - indexed for MEDLINE]

Sleep Med Rev. 2009 Dec;13(6):437-44. Epub 2009 Jul 10.
Obstructive sleep apnea and depression.
Harris M, Glozier N, Ratnavadivel R, Grunstein RR.

Australasian Sleep Trials Network, Adelaide Institute for Sleep Health, Flinders University, Adelaide, Australia. melanie.harris@flinders.edu.au
Abstract
There are high rates of depression in people with obstructive sleep apnea (OSA) in both community and clinical populations. A large community study reported a rate of 17% and reports for sleep clinic samples range between 21% and 41%. A large cohort study found OSA to be a risk factor for depression, but we are unaware of any longitudinal study of the reverse association. However correlations have not generally been found in smaller studies. Well-designed longitudinal studies are needed to examine temporal relationships between the two conditions and further research is needed to establish the role of confounders, and effect modifiers such as gender, in any apparent relationship. Symptoms common to OSA and depression, such as sleepiness and fatigue, are obstacles to determining the presence and severity of one condition in the presence of the other, in research and clinically. Sleep clinicians are advised to consider depression as a likely cause of sleepiness and fatigue. Several possible causal mechanisms linking OSA and depression have been proposed but not established. Patients who have depression as well as OSA appear worse off than those with OSA only, and depressive symptoms persist in at least some patients in short term studies of treatment for OSA. Direct treatment of depression in OSA might improve acceptance of therapy, reduce sleepiness and fatigue and improve quality of life, but intervention trials are required to answer this question.

PMID: 19596599 [PubMed - indexed for MEDLINE]

Curr Treat Options Neurol. 2010 Jan;12(1):1-15.
Sleep and headache.
Rains JC, Poceta JS.

Center for Sleep Evaluation, Elliot Hospital, One Elliot Way, Manchester, NH, 03103, USA, jrains@elliot-hs.org.
Abstract
OPINION STATEMENT: Headache has been linked to a wide range of sleep disorders that may impact headache management. There are no evidence-based guidelines, but the authors believe that literature supports the following clinical recommendations: 1. Diagnose headache according to standardized criteria. Specific diagnoses are associated with increased risk for specific sleep and psychiatric disorders. 2. Collect sleep history in relation to headache patterns. Screening questionnaires and prediction equations are cost-effective. 3. Rule out sleep apnea headache in patients with awakening headache or higher-risk headache diagnoses (cluster, hypnic, chronic migraine, and chronic tension-type headache); patients with signs and symptoms of obstructive sleep apnea warrant polysomnography and treatment according to sleep medicine practice guidelines. There is no evidence for suspending conventional headache treatment in suspected or confirmed cases of sleep apnea. Treatment of sleep apnea with CPAP may improve or resolve headache in a subset of patients. The impact on sleep apnea headache of other treatments for sleep apnea (eg, oral appliances, surgery, weight loss) is largely untested. At a minimum, sedative-hypnotic drugs should be avoided in suspected apneics until the sleep apnea is treated. 4. Among patients with migraine and tension-type headache, insomnia is the most common sleep complaint, reported by one half to two thirds of clinic patients. Patients who suffer from chronic migraine or tension-type headache may benefit from behavioral sleep modification. Pharmacologic treatment may be considered on a case-by-case basis, with hypnotics, anxiolytics, or sedating antidepressants used to manage insomnia, tailoring treatment to the symptom pattern. 5. Individuals with chronic headache are at increased risk for psychiatric disorders. Assessment for depression and anxiety may be warranted when either insomnia or hypersomnia is present. Psychiatric symptoms affect the choice of sedating versus alerting versus neutral pharmacologic agents for headache. 6. All headache patients, particularly those with episodic migraine and tension-type headaches, may benefit from inclusion of sleep variables in trigger management.

PATIENTS WITH UNTREATED SLEEP APNEA EXHIBIT "cortical excitability in patients with obstructive sleep apnea syndrome (OSAS) during wakefulness

A recent study in Sleep Med on altered Cortica Excitability in sleep apnea concluded that " This TMS-based study suggests that untreated severe OSAS patients have imbalanced cortical excitabilities that enhanced inhibition or decreased brain excitability when awake during the day."

This may be a cause of chronic headaches or migraines or other biochemical imbalances leading to stress disorders ofr depression.

I have included a few relevant pubmed articles below.

Sleep apne is the result of a TMJ disorder (http://www.nhlbi.nih.gov/meetings/workshops/tmj_wksp.pdf)

Neuromuscular Dentistry can help reduce incresed corticl activity, Treatment of sleep apnea can do the same.

Patients with sleep apnea have a smaller airway 24/7 that collapses at night. Correction of apnea and daytime jaw position may be ideal for all patients with chronic pain and sleep apnea.



Sleep Med. 2010 Oct;11(9):857-61.

Altered cortical excitability in patients with untreated obstructive sleep apnea syndrome.
Joo EY, Kim HJ, Lim YH, Koo DL, Hong SB.

Sleep Center, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Comment in:

Sleep Med. 2010 Oct;11(9):820-1.

Abstract
OBJECTIVE: To investigate cortical excitability in patients with obstructive sleep apnea syndrome (OSAS) during wakefulness.

METHODS: The authors recruited 45 untreated severe OSAS (all males, mean age 47.2 years, mean apnea-hypopnea index=44.6h(-1)) patients and 44 age-matched healthy male volunteers (mean apnea-hypopnea index=3.4h(-1)). The TMS parameters measured were resting motor threshold (RMT), motor evoked potential (MEP) amplitude, cortical silent period (CSP), and short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). These parameters were measured in the morning (9-10 am) more than 2h after arising and the parameters of patients and controls were compared. The Epworth Sleepiness Scale (ESS) and the Stanford Sleepiness Scale (SSS) were also measured before the TMS study.

RESULTS: OSAS patients had a significantly higher RMT and a longer CSP duration (t-test, p<0.001) compared to healthy volunteers. No significant difference was observed between MEP amplitudes at any stimulus intensity or between the SICI (2, 3, 5ms) and ICF (10, 15, 20ms) values of OSAS patients and healthy volunteers (p>0.05).

CONCLUSIONS: This TMS-based study suggests that untreated severe OSAS patients have imbalanced cortical excitabilities that enhanced inhibition or decreased brain excitability when awake during the day.

PMID: 20817550 [PubMed - in process]

Handb Clin Neurol. 2010;97:73-83.

Biological science of headache channels.
Pietrobon D.

Abstract
Several episodic neurological diseases, including familial hemiplegic migraine (FHM) and different types of epilepsy, are caused by mutations in ion channels, and hence classified as channelopathies. The classification of FHM as a channelopathy has introduced a new perspective in headache research and has strengthened the idea of migraine as a disorder of neural excitability. Here we review recent studies of the functional consequences of mutations in the CACNA1A and SCNA1A genes (encoding the pore-forming subunit of Ca(V)2.1 and Na(V)1.1 channels) and the ATPA1A2 gene (encoding the alpha(2) subunit of the Na(+)/K(+) pump), responsible for FHM1, FHM3, and FHM2, respectively. These studies show that: (1) FHM1 mutations produce gain-of-function of the Ca(V)2.1 channel and, as a consequence, increased glutamate release at cortical synapses and facilitation of induction and propagation of cortical spreading depression (CSD); (2) FHM2 mutations produce loss-of-function of the alpha(2) Na(+)/K(+)-ATPase; and (3) the FHM3 mutation accelerates recovery from fast inactivation of Na(V)1.5 channels. These findings are consistent with the hypothesis that FHM mutations share the ability to render the brain more susceptible to CSD, by causing excessive synaptic glutamate release (FHM1) or decreased removal of K(+) and glutamate from the synaptic cleft (FHM2) or excessive extracellular K(+) (FHM3).

PMID: 20816411 [PubMed - in pr

Handb Clin Neurol. 2010;97:47-71.

Pharmacology.
Bolay H, Durham P.

Department of Neurology, Gazi Hospital and Neuropsychiatry Centre, Gazi University, Besevler, Ankara, Turkey.

Abstract
Headache treatment has been based primarily on experiences with non-specific drugs such as analgesics, non-steroidal anti-inflammatory drugs, or drugs that were originally developed to treat other diseases, such as beta-blockers and anticonvulsant medications. A better understanding of the basic pathophysiological mechanisms of migraine and other types of headache has led to the development over the past two decades of more target-specific drugs. Since activation of the trigeminovascular system and neurogenic inflammation are thought to play important roles in migraine pathophysiology, experimental studies modeling those events successfully predicted targets for selective development of pharmacological agents to treat migraine. Basically, there are two fundamental strategies for the treatment of migraine, abortive or preventive, based to a large degree on the frequency of attacks. The triptans, which exhibit potency towards selective serotonin (5-hydroxytryptamine, 5-HT) receptors expressed on trigeminal nerves, remain the most effective drugs for the abortive treatment of migraine. However, numerous preventive medications are currently available that modulate the excitability of the nervous system, particularly the cerebral cortex. In this chapter, the pharmacology of commercially available medications as well as drugs in development that prevent or abort headache attacks will be discussed.

PMID: 20816410 [PubMed - in process]

Cephalalgia. 2010 Sep;30(9):1101-9. Epub 2010 Mar 19.

Cortical hyperexcitability and mechanism of medication-overuse headache.
Supornsilpchai W, le Grand SM, Srikiatkhachorn A.

Department of Physiology, Faculty of Medicine, Chulalongkorn University, Patumwan, Bangkok, Thailand.

Abstract
The present study was conducted to determine the effect of acute (1 h) and chronic (daily dose for 30 days) paracetamol administration on the development of cortical spreading depression (CSD), CSD-evoked cortical hyperaemia and CSD-induced Fos expression in cerebral cortex and trigeminal nucleus caudalis (TNC). Paracetamol (200 mg/kg body weight, intraperitonealy) was administered to Wistar rats. CSD was elicited by topical application of solid KCl. Electrocorticogram and cortical blood flow were recorded. Results revealed that acute paracetamol administration substantially decreased the number of Fos-immunoreactive cells in the parietal cortex and TNC without causing change in CSD frequency. On the other hand, chronic paracetamol administration led to an increase in CSD frequency as well as CSD-evoked Fos expression in parietal cortex and TNC, indicating an increase in cortical excitability and facilitation of trigeminal nociception. Alteration of cortical excitability which leads to an increased susceptibility of CSD development can be a possible mechanism underlying medication-overuse headache.

PMID: 20713560 [PubMed - in process]

ORAL APPLIANCES ARE A CONSERVATIVE METHOD OF TREATMENT ACCORDING TO THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE.

THE FOLLOWING PAGE FROM THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE OF THE NIH IS REPRINTED FROM http://www.ninds.nih.gov/disorders/sleep_apnea/sleep_apnea.htm

IN ADDITION TO THE WELL KNOWN SYMPTOM OF EXCESSIVE DAYTIME SLEEPINESS IT ALSO RECOGNIZES "morning headaches, trouble concentrating, irritability, forgetfulness, mood or behavior changes, anxiety, and depression AS ASSOCIATED DISORDER.

WHILE MANY IN THE MEDICAL SLEEP COMMUNITY ALWAYS LOOK AT CPAP AS THE FIRST LINE TREATMENT THE NINDS RECOGNIZES ORAL APPLIANCES AS A CONSERVATIVE TREATMENT OF SLEEP APNEA. THE FIRST LINE THERAPY FOR SLEEP APNEA ARE CONSERVATIVE METHODS "Most treatment regimens begin with lifestyle changes, such as avoiding alcohol and medications that relax the central nervous system (for example, sedatives and muscle relaxants), losing weight, and quitting smoking. Some people are helped by special pillows or devices that keep them from sleeping on their backs, or oral appliances to keep the airway open during sleep." AND CPAP IS COSIDERED A LESS CONSERVATIVE APPROACH ALONG WITH SURGERY. THE ARTICLE STATES "If these conservative methods are inadequate, doctors often recommend continuous positive airway pressure (CPAP), in which a face mask is attached to a tube and a machine that blows pressurized air into the mask and through the airway to keep it open. There are also surgical procedures that can be used to remove tissue and widen the airway.

THE SLEEP COMMUNTIY OFTEN MAKES CPAP THE FIRST AND SOMETIMES ONLY TREATMENT OF CHOICE. THE MORE RATIONAL APPROACH OF THE THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE OF THE NIH IS A FRESH APPROACH.

WHY CONSIDR CPAP A FIRST LINE TREATMENT WHEN MOST PATIENTS DO NOT TOLERATE CPAP.

CONSIDERING SLEEP POSITION, WEIGHT LOSS AND ORAL APPLIANCES AS CONSEVATIVE APPROACHES RECOGNIZE NOT JUST THE EFFECTIVENESS OF THESE TREATMENTS BUT ALSO THE CONSERVATIVE NATURE OF THESE TREATMENTS.

THE FOLLOWING IS INFORMATION FROM THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE SITE.

What is Sleep Apnea?
Sleep apnea is a common sleep disorder characterized by brief interruptions of breathing during sleep. These episodes usually last 10 seconds or more and occur repeatedly throughout the night. People with sleep apnea will partially awaken as they struggle to breathe, but in the morning they will not be aware of the disturbances in their sleep. The most common type of sleep apnea is obstructive sleep apnea (OSA), caused by relaxation of soft tissue in the back of the throat that blocks the passage of air. Central sleep apnea (CSA) is caused by irregularities in the brain’s normal signals to breathe. Most people with sleep apnea will have a combination of both types. The hallmark symptom of the disorder is excessive daytime sleepiness. Additional symptoms of sleep apnea include restless sleep, loud snoring (with periods of silence followed by gasps), falling asleep during the day, morning headaches, trouble concentrating, irritability, forgetfulness, mood or behavior changes, anxiety, and depression. Not everyone who has these symptoms will have sleep apnea, but it is recommended that people who are experiencing even a few of these symptoms visit their doctor for evaluation. Sleep apnea is more likely to occur in men than women, and in people who are overweight or obese.

Is there any treatment?

There are a variety of treatments for sleep apnea, depending on an individual’s medical history and the severity of the disorder. Most treatment regimens begin with lifestyle changes, such as avoiding alcohol and medications that relax the central nervous system (for example, sedatives and muscle relaxants), losing weight, and quitting smoking. Some people are helped by special pillows or devices that keep them from sleeping on their backs, or oral appliances to keep the airway open during sleep. If these conservative methods are inadequate, doctors often recommend continuous positive airway pressure (CPAP), in which a face mask is attached to a tube and a machine that blows pressurized air into the mask and through the airway to keep it open. There are also surgical procedures that can be used to remove tissue and widen the airway. Some individuals may need a combination of therapies to successfully treat their sleep apnea.
What is the prognosis?

Untreated, sleep apnea can be life threatening. Excessive daytime sleepiness can cause people to fall asleep at inappropriate times, such as while driving. Sleep apnea also appears to put individuals at risk for stroke and transient ischemic attacks (TIAs, also known as “mini-strokes”), and is associated with coronary heart disease, heart failure, irregular heartbeat, heart attack, and high blood pressure. Although there is no cure for sleep apnea, recent studies show that successful treatment can reduce the risk of heart and blood pressure problems.
What research is being done?

The National Institute of Neurological Disorders and Stroke (NINDS) and other institutes of the National Institutes of Health (NIH) conduct research related to sleep apnea in laboratories at the NIH, and also support additional research through grants to major medical institutions across the country. Much of this research focuses on finding better ways to prevent, treat, and ultimately cure sleep disorders, such as sleep apnea.