Can Sleep Apnea Cause Anxiety and Panic Attacks

Ann Fam Med. 2022 Jul; 13(4): 325–330.

Slumber Apnea and Risk of Panic Disorder

Vincent Yi-Fong Su, MD,^{1, 2, iii, ix, *} Yung-Tai Chen, Physician,^{3, 4, *} Wei-Chen Lin, MD,^{1, 3, 5} Li-An Wu, MD,⁶ Shi-Chuan Chang, PhD,^{1, 2, iii, seven} Diahn-Warng Perng, PhD,^{one, 2, iii} Wei-Juin Su, MSc,^{2, three} Yuh-Min Chen, PhD,^{2, three} Tzeng-Ji Chen, PhD,^{3, eight} Yu-Mentum Lee, Md,^{2, 3, 9} and Kun-Ta Chou, Doctor^{1, 2, 3, 9}

Vincent Yi-Fong Su

^aneCenter of Sleep Medicine, Taipei Veterans Full general Infirmary, Taipei, Taiwan

²Department of Chest Medicine, Taipei Veterans General Infirmary, Taipei, Taiwan

³School of Medicine, National Yang-Ming University, Taipei, Taiwan

⁹Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

Yung-Tai Chen

³Schoolhouse of Medicine, National Yang-Ming University, Taipei, Taiwan

⁴Department of Medicine, Heping-Fuyou Branch, Taipei City Hospital, Taipei, Taiwan

Wei-Chen Lin

¹Centre of Sleep Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

³School of Medicine, National Yang-Ming University, Taipei, Taiwan

⁵Department of Psychiatry, Taipei Veterans General Infirmary, Taipei, Taiwan

Li-An Wu

⁶Department of Radiology, Heping-Fuyou Co-operative, Taipei City Hospital, Taipei, Taiwan

Shi-Chuan Chang

¹Center of Sleep Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

ⁱⁱDepartment of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

³School of Medicine, National Yang-Ming University, Taipei, Taiwan

^viiConstitute of Emergency and Disquisitional Care Medicine, Schoolhouse of Medicine, National Yang-Ming University, Taipei, Taiwan

Diahn-Warng Perng

^aneCenter of Slumber Medicine, Taipei Veterans General Infirmary, Taipei, Taiwan

^twoSection of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

³School of Medicine, National Yang-Ming University, Taipei, Taiwan

Wei-Juin Su

²Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

³Schoolhouse of Medicine, National Yang-Ming Academy, Taipei, Taiwan

Yuh-Min Chen

²Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

³School of Medicine, National Yang-Ming University, Taipei, Taiwan

Tzeng-Ji Chen

ⁱⁱⁱSchool of Medicine, National Yang-Ming University, Taipei, Taiwan

⁸Department of Family Medicine, Taipei Veterans General Infirmary, Taipei, Taiwan

Yu-Chin Lee

²Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

³School of Medicine, National Yang-Ming University, Taipei, Taiwan

⁹Plant of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

Kun-Ta Chou

ⁱCenter of Sleep Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

^twoDepartment of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

^threeSchool of Medicine, National Yang-Ming University, Taipei, Taiwan

⁹Establish of Clinical Medicine, Schoolhouse of Medicine, National Yang-Ming University, Taipei, Taiwan

Received 2014 Nov 19; Revised 2022 Nov 22; Accustomed 2022 May 22.

Abstruse

PURPOSE

Epidemiological studies have identified a trend in the development of depressive and feet disorders post-obit a diagnosis of sleep apnea. The relationship between sleep apnea and subsequent panic disorder, withal, remains unclear.

METHODS

Using a nationwide database, the Taiwan National Health Insurance Enquiry Database, patients with sleep apnea and age-, sex activity-, income-, and urbanization-matched control patients who did non take sleep apnea were enrolled between 2000 and 2010. Patients with a prior diagnosis of panic disorder earlier enrollment were excluded. The 2 cohorts were observed until Dec 31, 2010. The primary endpoint was occurrence of newly diagnosed panic disorder.

RESULTS

A full of viii,704 sleep apnea patients and 34,792 control patients were enrolled. Of the 43,496 patients, 263 (0.60%) suffered from panic disorder during a mean follow-up menstruation of 3.92 years, including 117 (1.34%) from the sleep apnea accomplice and 146 (0.42%) from the command group. The Kaplan-Meier assay revealed a predisposition of patients with sleep apnea to develop panic disorder (log-rank test, P <.001). After multivariate adjustment, the hazard ratio for subsequent panic disorder among the sleep apnea patients was 2.17 (95% confidence interval, 1.68–2.81; P <.001).

CONCLUSIONS

Sleep apnea appears to confer a college hazard for hereafter development of panic disorder.

Keywords: sleep apnea syndromes, sleep-disordered breathing, panic disorder

INTRODUCTION

Obstructive sleep apnea is a common disorder characterized by repeated episodes of apnea and hypopnea during sleep owing to consummate or fractional plummet of the upper airway. ¹ Subsequent to apnea/hypopnea, patients with sleep apnea will be awakened by the resulting hypoxemia and so that they tin can resume breathing. Some patients may awake up feeling like they are choking or suffocating, thereby increasing their sense of stress. In the past decade obstructive sleep apnea has been constitute to exist linked to a variety of cardiovascular diseases, neurocognitive dysfunction, and behavioral disorders. ^2,three

Patients with sleep apnea may also have substantial comorbid mental disorders, such as low, anxiety, bipolar disorder, schizophrenia, mail service-traumatic stress syndrome, and substance corruption. ⁴ Panic disorder is an extreme pole of anxiety disorder with features of recurrent panic attacks. There are, all the same, few studies addressing the relationship betwixt slumber apnea and panic disorder, and most of these studies are small or lack an appropriate control group. ^5–9 A crossover report enrolling 12 patients with panic disorder who also had obstructive slumber apnea showed that they benefited from continuous positive airway pressure (CPAP) therapy, which decreased the panic attacks and reduced the use of alprazolam, suggesting an interaction of both diseases. ¹⁰ We therefore undertook this nationwide population-based study to elucidate the relationship of slumber apnea and subsequent panic disorder.

METHODS

Database

The National Health Insurance (NHI) is a mandatory universal wellness insurance program that since 1995 provides comprehensive medical service to almost all Taiwanese citizens. The National Health Inquiry Constitute in Miaoli (Taiwan) (http://nhird.nhri.org.tw/en) is in charge of the Taiwan NHI program and maintains the entire insurance claims database, namely, the National Wellness Insurance Research Database (NHIRD). The NHIRD consists of detailed health intendance data of more than 99% of the unabridged Taiwan's 23 1000000 population. ¹¹ The data used in this written report were retrieved from the Longitudinal Health Insurance Database 2000 (LHID2000), comprised of approximately 1,000,000 randomly sampled persons who were live in 2000; all the registration files and medical claims for the reimbursement of these individuals were collected from 1995 to 2010. The released database has been validated by the National Health Research Establish to be representative of the whole Taiwanese population ^eleven and is amidst the largest population-based databases in the earth; it is a resource for many published studies in Taiwan. ¹² Each patient'south personal identifiable information has been encrypted by the National Health Inquiry Establish using a consistent code, allowing linkage of claims belonging to individuals inside this database.

Study Sample and Control

The study was exempt from total review by the Institutional Review Board of Taipei Veterans Full general Hospital because the data sets consisted of de-identified secondary information. In this study, we enrolled developed patients (anile twenty years and older) who had newly diagnosed sleep apnea (International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes 780.51, 780.53, 780.57) during 2000 to 2010 as the study accomplice (sleep apnea accomplice). ¹³ The date of enrollment was defined as the date when slumber apnea was initially diagnosed. An age-, sexual practice-, monthly income-, and urbanization-matched group of patients who did not have sleep apnea served as the control group and were randomly selected from the same information sets. In both groups, patients with a medical history of panic disorder (ICD-9-CM codes 300.01, 300.21) before enrollment were excluded.

Variables

In this inquiry, general data, such as age, sex activity, monthly income, and urbanization were retrieved and matched betwixt groups. According to past studies, risk factors for panic disorder ¹⁴ and major comorbid conditions ³ linked to slumber apnea, including hypertension, coronary artery disease, cerebrovascular disease, asthma, chronic obstructive pulmonary disease, chronic kidney disease, dyslipidemia, paralysis, irritable bowel syndrome, mitral valve prolapse, premenstrual syndrome, hyperthyroidism, diabetes mellitus, drug corruption, cancer, bipolar disorder, obsessive-compulsive disorder, depression, phobia, and post-traumatic stress disorder, were assessed in our analyses. The Charlson comorbidity index, representative of baseline comorbidity profile, was also calculated and incorporated into the assay. ^fifteen

Matching

The control group of patients without sleep apnea was selected at a ratio of 4 control patients per ane patient with sleep apnea by means of incidence density sampling. ¹⁶ The command group was matched for each individual's historic period, sex, monthly income, urbanization, and enrollment year. Matching for the age and year of enrollment was immune within a tolerance range (±i twelvemonth). For the control group, the start appointment of follow-up was defined every bit the first date of clinical visit to a medical facility in the enrollment yr.

Main Event Measures

The endpoint of the study was divers as occurrence of panic disorder. All enrollees were observed from the date of enrollment until the first diagnosis of panic disorder or, if they were costless of panic disorder, until they died, withdrew from national health insurance, or reached the study finish engagement of Dec 31, 2010.

Statistical Assay

Extraction, matching, and computation of data were performed using the Perl programming language (version 5.12.two). A Microsoft SQL Server 2012 (Microsoft Corp) was used for data linkage, processing, and sampling. Statistical analysis was performed using SPSS 18.0 software (SPSS, Inc). All data were expressed as means plus or minus standard deviations or as a per centum unless otherwise stated. Comparing betwixt 2 groups was made by contained Student's t tests for continuous variables or Pearson's χ² test for categorical variables, every bit appropriate. Survival analysis was performed using the Kaplan-Meier method, with significance based on the log-rank exam. A Cox proportional hazard model was used for multivariate aligning. To better elucidate slumber apnea as a dependent chance factor for panic disorder, we performed multivariate adjustments in v different models. The take a chance ratios were obtained subsequently adjusting age and sex in model 1 and further aligning for monthly income, urbanization, and outpatient visits in model two. In models 3 through v, boosted adjustments were made for psychiatric comorbidities, all comorbidities (every bit listed in Tabular array one), and the Charlson comorbidity score. Statistical significance was inferred at a 2-sided P value of <.05.

Table i

Demographic and Clinical Characteristics of Patients

Characteristics	Sleep Apnea (n = 8,704)	Controls (n = 34,792)	P Value
Mean age, y (SD)	47.nine (xv.one)	47.nine (15.1)	.963
Male, No. (%)	5,490 (63.07)	21,943 (63.07)	.993
Monthly income, No. (%)			>.999
Dependent	1,539 (17.68)	half dozen,156 (17.69)
NT$0-NT$19,100a	2,001 (22.99)	8,002 (23.00)
NT$xix,100-NT$42,000a	3,713 (42.66)	14,852 (42.69)
>NT$42,000a	1,451 (16.67)	5,782 (sixteen.62)
Urbanization, No. (%)			one.000
Level 1 (highest)	5,188 (59.60)	20,750 (59.64)
Level two	2,901 (33.33)	11,598 (33.33)
Level three	503 (five.78)	2,003 (5.76)
Level 4 (lowest)	112 (ane.29)	441 (1.27)
Charlson comorbidity score, No. (%)			<.001
0	i,982 (22.77)	14,216 (forty.86)
i	2,074 (23.83)	8,323 (23.92)
2	ane,561 (17.93)	4,919 (14.14)
3	1,108 (12.73)	2,822 (8.11)
≥4	1,979 (22.74)	4,512 (12.97)
Outpatient visits in the past 1 yr, No. (%)			<.001
0–5	122 (1.40)	2,854 (8.21)
6–ten	one,110 (12.75)	8,608 (24.74)
11–15	1,342 (fifteen.42)	6,946 (19.96)
>xv	6,130 (seventy.43)	16,384 (47.09)
Comorbid disease, No. (%)
Hypertension	3,429 (39.40)	nine,204 (26.45)	<.001
Coronary artery disease	ii,198 (25.25)	4,992 (fourteen.35)	<.001
Cerebrovascular disease	1,254 (14.41)	2,964 (viii.52)	<.001
Asthma	1,604 (18.43)	three,721 (ten.69)	<.001
COPD	2,392 (27.48)	5,695 (16.37)	<.001
Chronic kidney disease	902 (x.36)	2,227 (half-dozen.40)	<.001
Dyslipidemia	2,923 (33.58)	7,271 (20.ninety)	<.001
Paralysis	130 (1.49)	353 (1.01)	<.001
Irritable bowel syndrome	1,476 (sixteen.96)	3,405 (9.79)	<.001
Mitral valve prolapse	505 (5.fourscore)	1,072 (3.08)	<.001
Premenstrual syndrome	57 (0.65)	132 (0.38)	<.001
Hyperthyroidism	464 (5.33)	1,081 (3.11)	<.001
Diabetes mellitus	1,831 (21.04)	five,290 (15.20)	<.001
Drug abuse	332 (three.81)	742 (2.xiii)	<.001
Cancer	819 (9.41)	2,064 (5.93)	<.001
Bipolar disorder	31 (0.36)	60 (0.17)	.001
Obsessive-compulsive disorder	44 (0.51)	57 0.16)	<.001
Depression	384 (4.41)	590 (ane.70)	<.001
Phobia	23 (0.26)	37 (0.eleven)	<.001
PTSD	9 (0.10)	vii (0.02)	<.001

RESULTS

Figure 1 displays a flowchart of enrollment and follow-upward. The basic characteristics of the slumber apnea cohort and the control group are shown in Tabular array one. Compared with the command group, the sleep apnea cohort had higher percentages of comorbidities, higher Charlson comorbidity scores, and more medical visits in the past year. During a mean follow-up period of 3.92 years, there were more than panic disorder events among the sleep apnea cohort as compared with the command group (117 [1.34%] vs 146 [0.42%]; P <.001]. Sleep apnea patients had a significantly higher risk for incident panic disorder than the comparison group (log-rank exam, P <.001, Effigy two). Incidences in the sleep apnea accomplice and the command group were 33.86 and 10.73 persons per 10,000 person-years, respectively (P <.001). Comparing groups with and without panic disorder, those patients with incident panic disorder were predominately female (54.37%) and had a higher percentage of hypertension, coronary artery disease, cerebrovascular illness, asthma, chronic obstructive pulmonary affliction, chronic kidney disease, dyslipidemia, irritable bowel syndrome, mitral valve prolapse, hyperthyroidism, diabetes mellitus, bipolar disorder, obsessive-compulsive disorder, depression, and phobia.

Flow diagram summarizing the process of enrollment and follow-up.

Cumulative incidence of panic disorder in patients with sleep apnea and the matched accomplice.

Multivariate assay in 5 different models consistently indicated that slumber apnea was independently associated with incident panic disorder (Tabular array ii). The fully adapted hazard ratio in the model 5 was ii.17 (95% CI, 1.68–ii.81; P <.001). The subgroup analyses are presented in Figures 3 and 4 of the Supplemental Appendix (http://www.annfammed.org/content/13/4/325/suppl/DC1). It is noteworthy that the hazard ratios of all sleep apnea models were statistically significantly higher in their counterparts devoid of a given comorbidity, suggesting an contained office of slumber apnea in evolution of panic disorder.

Table 2

Series Multivariate Adjustment Showing Sleep Apnea equally a Take a chance Cistron for Incident Panic Disorder

Adjustment Model	Hazard Ratio	95% CI	P Value
Crude, unadjusted	three.16	two.47–four.02	<.001
Model anea	3.17	2.48–4.04	<.001
Model 2b	2.62	2.04–iii.37	<.001
Model 3c	2.47	i.92–3.17	<.001
Model fourd	2.21	1.71–2.86	<.001
Model 5eastward	two.17	ane.68–two.81	<.001

Give-and-take

In this study, we are able to show that sleep apnea is an independent risk factor for incident panic disorder. Considering the linkage of sleep apnea to of import health consequences, our findings may further broaden the spectrum of its comorbidities. To our knowledge, this cohort report is the largest probing into this issue. In contrast with other published literature, ^v–9 this study addressed the temporal relationship between slumber apnea and panic disorder and provided an appropriate control grouping for comparing every bit well.

Sleep apnea has been reported to be associated with several mental disorders, including depression, anxiety, posttraumatic stress disorder, psychosis, and bipolar disorders. ^4,17 Interestingly, psychological symptoms may correlate with the degree of hypoxia in such patients and can be improved after CPAP therapy. ^18,19 Patients with coexisting sleep apnea and mental disorders responded less well to antipsychotic medications than did those who did non take sleep apnea. ²⁰ Thus, identifying patients with overlapping diagnoses of mental disorders and sleep apnea would assistance to improve their treatment outcomes through more than aggressive pharmacotherapy and CPAP therapy.

There take been few studies addressing the relationship of slumber apnea and panic disorder; nearly were instance reports, ^5–seven one was a cross-sectional written report ⁸ and one was a small-calibration case-control study, ^nine which has not immune for a solid decision. Our results, derived from a large-scale database, provide a closer look at the relationship of the 2 disorders. Based on our results, sleep apnea conferred a college risk for panic disorder, even afterwards a relatively curt follow-up flow (three.9 years) in an older population (age 47.9 years on average). In a randomized crossover study, ^ten Takaesu et al has shown that CPAP therapy could significantly reduce the frequency of panic attacks, the panic disorder severity scale score, and the employ of alprazolam for panic set on in 12 patients with obstructive sleep apnea and panic disorders.

Given that panic disorder in this population may be attenuated after CPAP treatment, the bodily prevalence of panic may be higher than establish in our electric current written report, a possibility that may further strengthens our conclusion. Moreover, testify and so far favors the inference that the clan between sleep apnea and panic disorder results primarily from an influence in one management (ie, from a history of sleep apnea to first panic attack). The possibility of a bidirectional relationship between slumber apnea and panic attacks awaits further exploration.

The link between sleep apnea and panic disorder could exist explained in several ways. Frequent arousals from sleep (slumber fragmentation), awakening with feelings of choking or suffocating, and daytime sleepiness take been proposed as mechanisms of feet in obstructive sleep apnea. ²¹ Additionally, episodes of apnea/hypopnea resulting in intermittent hypoxemia (and possibly hypercapnia) may facilitate oxidative stress-related functional deterioration and central nervous system injury, thereby increasing the risk of panic disorder. ^22,23 Functional and structural neuroimaging studies show that sleep apnea alters brain structure with time, leading to a decrease in grayness thing in the hippocampus, frontal lobe, and the anterior cingulate cortex. ^24–26 Impairment to similar regions are also seen in the patients with panic disorders. ^27–30 Lastly, hypercapnia may play a role based on the prove that panic attack can exist provoked past inhalation of carbon dioxide. ³¹

The strengths of our study are its nationwide, population-based study design and that all respiratory and psychiatric practices were covered in the database, which allowed us to trace all cases of newly diagnosed sleep apnea and panic disorder. Additionally, the large sample size in our study offered substantial statistical power for detecting real, even subtle, differences between the 2 cohorts. Because participation in the NHI is mandatory, and all Taiwanese can employ medical care with low copayment, the follow-up of each patient was completed with the lowest referral bias.

There are several limitations in our study. Starting time, diagnoses of slumber apnea and panic disorder that rely on authoritative claims information recorded by physicians or hospitals may be less authentic than diagnoses made in a clinical, prospective setting. Sleep apnea is ofttimes underdiagnosed, maybe generating a misclassification bias. All the same, the nondifferential misclassification bias was toward the goose egg; if the misclassification were corrected, and then our positive conclusion would exist strengthened, that is, our results would be more pregnant. Alternatively, some patients with panic disorder might not have used health care, either earlier or after enrollment, and therefore might not take appeared in the claims data sets every bit having panic disorder, which may provide a source of bias. 2d, patients' body mass alphabetize and smoking history, which may impact the propensity to obstructive sleep apnea, were not available in the database. Third, we could not further classify sleep apnea into obstructive type or primal type, because the 2001 version of the ICD-ix-CM coding did not split the ii subtypes of sleep apnea. Fifty-fifty so, obstructive sleep apnea was reported to be the predominant (>90%) blazon of sleep apnea by Bixler et al, ³² which is compatible with the our results (>99%) in a previous study. ¹³ Finally, the external validity of our findings may be a business organization considering our patients were almost all Taiwanese. Generalization of our results to non-Asian populations needs further verification.

Sleep apnea may be a risk factor for panic disorder. Clinicians should be aware of panic disorder as a comorbid condition in sleep apnea patients. Hereafter prospective research is needed to confirm our finding and elucidate the possible underlying mechanisms.

Footnotes

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508172/

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