Psychosomatics 40:491-496, December 1999
© 1999 The Academy of Psychosomatic Medine
Economic Consequences of Comorbid Depression, Anxiety, and Allergic Rhinitis
Brian Cuffel, Ph.D.,
Marianne Wamboldt, M.D.,
Larry Borish, M.D.,
Sean Kennedy, B.S., and
Jodi Crystal-Peters, B.A.
Received January 26, 1999; revised May 12, 1999; accepted May 28, 1999. From Behavioral Health Sciences, United Behavioral Health; Department of Medicine, National Jewish Medical and Research Center; Department of Psychiatry, University of Colorado Health Sciences Center; and the The MEDSTAT Group. Address correspondence and reprint requests to Dr. Cuffel, United Behavioral Health, 425 Market Street, 27th Floor, San Francisco, CA 94105–2426.
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ABSTRACT
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The present study extends prior work on the association between allergic rhinitis (AR) and common mental disorders by testing three related hypotheses: 1) that AR is associated with increased rates of depression and anxiety disorders in a large insured population, 2) comorbid AR, depression, and anxiety are associated with increased health and mental health expenditures, and 3) allergy treatment moderates the association between increased expenditures and comorbid AR, depression, and anxiety. Data are from MARKETSCAN®, a large health care claims database of over 600,000 privately insured persons. Results indicate that AR is associated with higher rates of depression and anxiety disorder. Outpatient health care expenditures were increased by an average annual amount of $207 when AR and anxiety disorder were comorbid and $363 when AR and depression were comorbid. Finally, prescription treatment of AR moderated the increased expenditures associated with comorbidity.
Key Words: Depression • Anxiety • Economics
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INTRODUCTION
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The increased prevalence and deleterious consequences of depression and anxiety disorders are well documented in persons having severe medical problems such as myocardial infarction and cancer.1–3 Depression and anxiety disorders occur in 10% to 17% of U.S. citizens yearly, and their rates in severely ill medical patients are considerably higher.4,5
Few studies have examined the rates of mental disorder in less disabling but much more prevalent health problems such as allergic rhinitis. Allergic rhinitis (AR) is a highly prevalent immunologic disease affecting 5%–22% of the American population and has been linked to both depression and anxiety in symptom phenomenology and etiology.6,7 Physical symptoms of AR include sneezing; nasal congestion; rhinorrhea; otitis; headache; itching of the nose; and itching, reddening, and watering of the eyes.
Psychosocial symptoms of AR resemble symptoms of depression and anxiety and include chronic fatigue, decreased appetite, poor school performance, poor self-image, absence from work, irritability, and moodiness.8–11 An association between depression and/or anxiety and allergies has been found in nonclinical samples,12,13 in primary care patients with known viral infections,14 and in patients with depression or panic disorder.15–18 However, other groups have failed to find an association between clinically diagnosed allergies and behavioral symptoms.19 Relatively small sample sizes in these studies may have led to contradictory results.
Whether the comorbidity of depression or anxiety and AR increases the morbidity of AR or depression or anxiety disorders has not been studied. The prevalence of these disorders suggests that they may have significant economic consequences for health care systems. The present study presents information on treated prevalence and economic consequences of comorbid depression, anxiety, and allergies by using information from a large, health care claims database. The study has three aims: 1) to ascertain the comorbidity of depression, anxiety disorders, and AR in a large, national sample of health care users; 2) to estimate the effects of comorbid major depression, anxiety, and AR on overall medical costs; and 3) to determine whether the economic effects of comorbidity are moderated by medication prescribed for AR.
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METHODS
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Design Overview
The prevalence and economic consequences of comorbid mental health and allergy conditions were examined in a population of over 600,000 privately insured persons in the United States in 1995. Data were from MarketScan®,7 a national health care claims database maintained by the MEDSTAT Group. MarketScan contains information on patient demographics, treatment, diagnoses, utilization, and payments for persons using services in indemnity, point-of-service, and PPO plans.
Sample Selection
The sample consisted of persons receiving a depression, anxiety disorder, or AR diagnosis during the study year (1995). A total of 140,103 persons (22% of all insured persons) received at least one of the study diagnoses during the year. Individuals were considered depressed if he/she 1) received an International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis of major depression, neurotic depression (dysthymia), brief depressive reaction (adjustment disorder with depressed mood), prolonged depressive reaction, or depressive disorder; or 2) submitted two or more claims for an antidepressant medication. Although the latter group may include persons with other diagnoses (e.g., pain syndromes), their inclusion was considered important to address the well-documented problem of underrecognition and misdiagnosis of depression in primary care settings.20
Individuals were considered to have an anxiety disorder if they received an ICD-9-CM diagnosis of panic disorder, generalized anxiety disorder, simple phobia, agoraphobia, social phobia, obsessive-compulsive disorder, acute reaction to stress, adjustment reaction with anxious mood, posttraumatic stress disorder, or other unspecified phobia or anxiety state.
Allergies were inferred from the presence of an AR diagnosis or the presence of two or more prescriptions for allergy treatment in the claims data. AR diagnoses included nonseasonal and seasonal allergies, hay fever, and spasmodic rhinorrhea. The selection criteria may not have excluded other conditions such as perennial nonallergic rhinitis, sinusitis, otitis, urticaria and recurrent episodes of choryza, for which anti-allergy therapeutics may have been prescribed. However, AR is the most probable diagnosis in patients receiving a prescription for AR treatment.
Expenditures
Expenditures were estimated by the average amount paid per patient overall and separately for inpatient, outpatient, and pharmacy services. In some analyses, we isolated payments for mental health inpatient, outpatient, and pharmacy services.
Statistical Analyses
Log-linear models and tetrachoric correlations were used to test for an association among anxiety, depression, and AR.16,21 Medical and mental health expenditures were modeled as a function of their log-transformed values by using ordinary least squares regression. Predictor variables included the presence or absence of diagnoses in the claims for anxiety, depression, and AR. Also included were the AR * Anxiety and AR * Depression interaction terms that coded for the effects of comorbidity. Covariates to the model included age and sex. Log expenditures were retransformed back to expenditures in dollars by using the nonparametric smearing technique.22,23 A final set of regression models estimated the moderating effects of AR treatment in the subset of persons having AR by using two interaction terms: Anxiety * Treatment and Depression * Treatment.
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RESULTS
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Among all persons insured, 13% (n=85,298) received an AR diagnosis, 9.3% (n=59,529) received a depression diagnosis, and 2.2% (n=14,582) received an anxiety disorder diagnosis. Males comprised 38.9% of the sample and persons age 45–54 were the most prevalent age group (25.6%). The other age groups represented in the data were 0–17 (16.1%), 18–34 (17.6%), 35–44 (21.3%), 55–64 (18.9%), and over 65 years of age (0.4%).
Comorbidity of Depression, Anxiety, and Allergies
The prevalence of depression, anxiety, and comorbid depression and anxiety for allergic and nonallergic samples is shown in Table 1. Results are consistent with the hypothesis that, among persons seeking health care, rates of depression and anxiety are higher in the allergy than in the nonallergy patients.
The log-linear model was highly statistically significant for the allergy-depression association: logistic regression (LR)(1)=1777.1, P<0.0001. The odds of a depressive disorder are approximately 1.7 (95% confidence interval [CI]=1.63, 1.73) times higher in the AR than in the non-AR sample, yielding a tetrachoric correlation of 0.145 (95% CI=0.138, 0.151) and a small effect size. The log-linear model was also statistically significant for the anxiety-AR association (LR=45.4, P<0.0001, respectively). The odds of anxiety disorder are about 1.41 times higher (95% CI=1.35, 1.47) in the AR than in the non-AR sample, yielding a tetrachoric correlation of 0.079 (95% CI=0.068, 0.089).
Economic Cost of Comorbidity
Comorbid depression, anxiety, and allergies appear to be related to health expenditures. Table 2 contains the regression coefficients for log-expenditure models, including the simple and interactive effects of depression, anxiety, and AR. Log-expenditure models indicate that outpatient expenditures for comorbid AR and depression were higher than the sum of either condition alone. Retransformation from log-expenditures to dollars suggests that comorbidity is associated with an added cost of $363 per user per year. Total mental health expenditures were also higher in comorbid allergy and depression. Estimates suggest $15.56 in added mental health expenses per mental health user annually. Among persons who were prescribed medication, comorbid AR and depression raised mental- health–related prescription expenditures an estimated $202 per year.
Similar findings were observed for comorbid anxiety and AR, as can be seen by examining the Treatment * Anxiety coefficients in Table 2. Comorbid anxiety-AR was associated with significantly higher outpatient and pharmaceutical expenditures. Retransforming to real dollars, outpatient medical expenditures were $207 higher when allergies were comorbid; with anxiety disorder and pharmaceutical, expenditures were $6.31 higher.
Effects of Treatment
A final set of regression equations were estimated to test whether allergy treatment mediated the higher medical and mental health expenditures observed when anxiety and depression were comorbid with AR. Treatment was considered a mediator when the Treatment * Anxiety or Treatment * Depression interaction was negative in magnitude and statistically significant. Analyses of treatment effects were limited to the subsample of health care users with allergies.
Among those with AR during the year, AR treatment moderated the relationship between depression and total, outpatient, and pharmaceutical expenditures, as shown by the Treatment * Depression interaction in Table 3. In real dollars, AR treatment is associated with lower total expenditures by an estimated $83 per health care user per year. Outpatient expenditures were lower by an average of $151 per year. Estimates for pharmaceutical expenditures show an average reduction of $200 per user of AR medication.
AR treatment also appeared to moderate the increased costs associated with AR-anxiety comorbidity. The AR Treatment * Anxiety interaction was significant for total medical expenditures and for pharmaceutical expenditures, as shown in Table 3. Estimated expenditure reductions on a per user per year basis were $141 per user per year. AR treatment did not appear to mediate the association between mental health expenditures and comorbid anxiety and depression, as all interaction terms were nonsignificant for the mental health service categories.
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DISCUSSION
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AR was associated with higher rates of depressive and anxiety disorders in a large, national sample of health care users. Comorbidity was associated with higher rates of medical expenditures, particularly outpatient medical and mental health expenditures for comorbid AR and depression. However, allergy treatment appeared to lessen the extent to which AR-depression and AR-anxiety comorbidity increased medical expenditures.
While there is evidence that depression and the atopic disorders may share a common genetic predisposition,13 there are numerous additional explanations for the higher than expected concordance of AR with depression and anxiety observed in this study. Persons with depression and other psychiatric disorders associated with increased somatization may be more likely to attend to symptoms of AR and seek health care.24 As many as 20%–40% of the U.S. population are estimated to have allergic rhinitis, yet fewer than half of these currently seek health care.25 The treated prevalence rate in this study alone was 13%. Depressed or anxious persons may be more likely to be seek health care for AR because of increased somatic concern and selective attention to physical symptoms.
Similarly, persons already under treatment for an atopic disorder have been introduced to the health care system, and an indolent depression or anxiety disorder—which might otherwise have gone unnoticed—may be diagnosed and treated. The fact that the rates of comorbidity are similar to that found in a community sample, however, suggests that the magnitude of any such bias may not be great (unpublished manuscript, Wamboldt MZ and Hewitt JK, Familial association between atropy and depression in adult Finnish twins).
Another possibility is that depression may directly influence the development of an atopic disorder. Depression itself may be an inflammatory process.26 Depressed patients have higher blood levels of monocytes, memory T-cells; interleukin-2 receptor-bearing cells; and pan T, pan B, and T cytotoxic cells than patients with dysthymia, who in turn have higher levels than control subjects. Depression is associated with abnormal hypothalamic-pituitary-adrenal axis function, with increased cortisol production, and abnormal cortrisyn-stimulation tests27,28 and this effect may also contribute to immune deviation toward the development of allergic immune response.29
It is similarly possible that the presence of atopy may predispose toward the development of depression and anxiety. Atopy is associated with systemic immune activation and cytokine production,30 which may contribute to symptoms similar to depression, such as lethargy, fatigue, somnolence, decreased cognition, difficulty concentrating, and decreased sleep and appetite.31,32 An alternative influence is through the association of atopy with sleep disturbances resulting from nasal congestion and central and peripheral sleep apneas.33 Sleep disturbances may produce daytime somnolence, fatigue, diminished cognition, mood changes, and other symptoms that may either exacerbate or be misdiagnosed as depression.
The most likely hypothesis substantiated by current evidence is that atopic reactions are known to create cholinergic system supersensitivity and beta-adrenergic system subsensitivity in the autonomic nervous system.34 That same imbalance of the cholinergic/adrenergic system in the central nervous system is known to occur in endogenous depression.35,36 If the allergic reaction leads to the same effect in the central nervous system, that is, an increase in cholinergic mediators and a relative decrease in adrenergic mediators, then an acute allergic reaction can thereby neurochemically predispose the allergic person to endogenous depression.6
Finally, the use of sedating antihistamines may produce or exacerbate symptoms of depression and make atopy more refractory to antidepressive therapy.
Several aspects of the data limit generalizability of the present study findings. The observational study design does not control for selection biases regarding the AR treatment effect. Persons receiving AR treatment may differ from those not receiving treatment in ways that affect health care expenditures. The magnitude and direction of any selection bias cannot be estimated from this data and can best be controlled through randomized studies of AR treatment.
Allergies were inferred from either the presence of an AR diagnosis or two or more prescriptions for allergy treatment. Allergy treatments included topical and systemic antihistamines, or topical nasal corticosteroids. Because of the wide-ranging use of these agents, these ascertainment criteria may overestimate the prevalence of AR. However, AR is the most likely diagnosis in subjects receiving a prescription for this class of medications and many of the conditions for which these classes of medications are used complicate allergic diseases.
An additional confounding variable may derive from the fact that treated and untreated persons may have used over-the-counter (OTC) medications in proportions that cannot be determined from health care claims data. Prescription medications are far more efficacious and have far fewer side effects than OTC medications.37 Thus, our results may derive from 1) the institution of therapy in subjects who would otherwise be left untreated; 2) the elimination of side effects of OTC medications (e.g., sedation and decreased cognition); and 3) the institution of a regimen that successfully reduces or eliminates symptoms of AR. It will be important for future studies to determine which of these possibilities influences our observations on the benefits of allergy therapy.
Despite the observational nature of the data, the associations observed in the present study have important predictive value for health care systems. The data support the notion that AR is linked to depression and anxiety, with economic consequences for large systems of care. Although effect sizes are small, the cumulative economic impact of comorbidity may be high in large populations. Results suggest that mental health providers should inquire about allergies, allergens, and other seasonal and environmental triggers that may be related to the frequency and severity of depressive and anxiety-related episodes. Similarly, providers treating AR should inquire about periods of depression and anxiety and recommend a mental health evaluation for AR that is associated with a depressed syndrome of low mood, chronic fatigue, loss of motivation or appetite, and sleeplessness that persists for 2 or more weeks despite AR treatment.
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ACKNOWLEDGMENTS
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The authors thank Schering-Plough for support of this research.
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ABSTRACT
INTRODUCTION
