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Antidepressant Treatment of Caregivers of Children With Asthma

Received September 15, 2006; revised November 21, 2006; accepted December 4, 2006. From the Depts. of Psychiatry, Pediatrics, and Internal Medicine, University of Texas Southwestern Medical Center at Dallas; and the Dept. of Psychiatry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo. Send correspondence and reprint requests to E. Sherwood Brown, M.D., Ph.D., University of Texas Southwestern Medical Center 5323 Harry Hines Blvd., Dallas, TX 75390-8849. e-mail: Sherwood.Brown{at}UTSouthwestern.edu
© 2008 The Academy of Psychosomatic Medicine

ABSTRACT

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BACKGROUND: Depression is common in caregivers of children with asthma and is associated with increased emergency service utilization for the child’s asthma. OBJECTIVE: This pilot study examined the impact of antidepressant treatment of depressed caregivers on the caregiver’s depression and the child’s asthma. METHOD: Eight depressed caregivers of children with asthma were given up to 6 months of algorithm-based antidepressant therapy. RESULTS: Caregiver depressive symptoms and the child’s asthma symptoms improved significantly. CONCLUSION: Unscheduled clinic visits showed a trend toward significant decrease. Larger trials are needed to confirm these findings and identify mechanisms linking improvement in caregiver depression with improvement in their child’s asthma.

INTRODUCTION

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Asthma is a common and severe medical illness with increasing prevalence, morbidity, and mortality, especially in minority communities. In the past two decades, the prevalence of asthma has increased by 75%;¹ asthma-related hospitalizations have increased by over 70%; and the asthma mortality rate has doubled.² Depression and anxiety are common in persons with asthma, and are associated with increased asthma-related morbidity, mortality, and unscheduled service utilization.³

Psychiatric symptoms are also common in caregivers of children with asthma. Wade et al.⁴ found, on the basis of Brief Symptom Severity (BSI) Global Severity scores, that 50% of a group of 1,628 caregivers of inner-city children with asthma had significant psychiatric symptom severity.⁴ Weil et al.⁵ reported that caregivers of children with asthma with BSI scores consistent with significant psychopathology were twice as likely to report an asthma-related hospitalization by the child in the previous 9 months as those with scores below the cutoff.⁵ Bartlett et al.⁶ found that 47% of mothers of inner-city children with asthma had clinically significant depressive symptoms that were associated with a 40% greater likelihood of an emergency room visit by the child in the following 6 months.⁶ Waxmonsky et al.⁷ recently reported clinically significant depressive symptoms, on the basis of Beck Depression Inventory (BDI) scores in 43% of mothers and 32% of fathers of children at an asthma clinic. Parents’ BDI scores correlated significantly with depressive symptom severity in the child.⁷

We recently assessed 175 caregivers of children hospitalized with an asthma exacerbation by a structured diagnostic interview for psychiatric disorders and the BSI.⁸ Depression and anxiety symptoms and syndromes were common in the caregivers, with 24% having a current major depressive episode and 21% an anxiety disorder, on the basis of DSM–IV criteria. Elevated BSI scores or the presence of an anxiety disorder in the caregiver was associated with significantly more asthma-related hospitalizations by the child in the past 12 months. Major depressive disorder (MDD) in the caregiver was associated with significantly more unscheduled clinic appointments by the child in the previous 12 months. The number of asthma-related hospitalizations in the past 12 months showed significant positive correlations with caregiver BSI scores.⁸

In this article, findings are reported from a pilot intervention study exploring the impact of antidepressant treatment on the caregiver’s depression symptoms and the child’s asthma. The aims were to 1) determine whether antidepressant treatment was effective for treating the caregiver’s depression symptoms; and 2) determine whether the intervention was associated with improved asthma outcomes in the child, including a shift away from unscheduled treatment.

METHOD

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Primary caregivers (as determined by the caregiver’s report) of children hospitalized with an asthma exacerbation were assessed for the presence of a current major depressive disorder by use of methods described in detail elsewhere.⁸ If the caregivers had current MDD on the basis of the Mini-International Neuropsychiatric Interview (MINI),⁹ a standard, structured psychiatric interview using DSM–IV criteria was performed. IRB-approved written informed consents from both the caregiver and child were obtained for an intervention study and, if they agreed to participate, an appointment was arranged for further outpatient assessment at the principal investigator’s office. Included were caregivers age 18 to 70 years with a current diagnosis of MDD and ability to speak and read either English or Spanish, who served as the primary caregiver for the child with asthma. Excluded were caregivers with mental retardation or other severe cognitive disability that could impair their ability to provide informed consent and members of a vulnerable population (jail or prison inmates, pregnant or nursing women), patients at risk for suicide, defined by multiple recent suicide attempts (>3 in the past year) or any attempt in the past month, or current active suicidal or homicidal ideation; caregivers with severe or life-threatening medical illness that might make completion of the study unlikely; and caregivers with treatment-refractory depression, defined as failing 3-or-more adequate trials of antidepressants.

Children were boys or girls, English- or Spanish-speaking, ages 5 to 16, and hospitalized at Children’s Medical Center of Dallas, TX, for a status asthmaticus. Children with mental retardation were excluded.

Assessments administered at baseline and every 4 weeks during the 24-week study for the caregiver consisted of the Hamilton Rating Scale for Depression (Ham–D),¹⁰ a 17-item, 0–2 and 0–4 scale, clinician-rated assessment of the severity of depressive symptoms; the Quick Inventory of Depressive Symptomatology–Self Report (QIDS–SR),¹¹ a 16-item self-rated measure of depressive symptom severity on a 0–3 scale; and the Pediatric Asthma Caregiver’s Quality of Life Questionnaire (PedACaregiverQoLQ),a 13-item self-report measuring domains of activity limitations and emotional functioning on a 1–7 scale.¹²

The child was assessed at baseline and every 4 weeks with the Pediatric Asthma Symptom Scale (PedAsthmaSS) Face-to-Face Version, an 8-item, 1–5 scale of asthma symptom frequency in the past 4 weeks;¹³ the Pediatric Asthma Quality of Life Questionnaire (PedAQoLQ), a 23-items self-rated scale assessing domains of symptoms, activity limitations, emotional functioning, on a 1–7 scale;¹⁴ and the Children’s Depression Inventory–Short Form (CDI–SF), a 10-item self-report of depressive symptoms, on a 0–2 scale.¹⁵ Pulmonary function was measured on the child by research staff using a portable spirometer. The caregiver and child assessments were conducted by different raters, who were blind to information provided by the other study participant (i.e., caregiver rater did not have information on the child’s status). Caregivers were given open-label, algorithm-based antidepressant treatment for 6 months at no cost by use of a modified and simplified version of the Texas Medication Algorithm Project guideline for the treatment of MDD.¹⁶ Unless contraindicated, treatment began with escitalopram, with a change to bupropion after 8 weeks if no response was observed, and switch to mirtazapine or nortriptyline after an additional 8 weeks if needed. Response was defined as 50% reduction on Ham–D score. Dose titrations of antidepressants, if needed, occurred at 4-week intervals. Augmentation with lithium was allowed.

Caregivers and children returned at Weeks 4, 8, 12, 16, 20, and 24, at which time depressive symptoms in the caregiver (Ham–D, QIDS–SR) and child (CDI–SR), asthma symptoms (PedAsthmaSS) and peak expiratory flow in the child, asthma-service utilization in the child (asthma-related hospitalizations, emergency room visits, unscheduled clinic visits), and quality of life in the caregiver (PedACaregiverQoLQ) and child (PedAQoLQ) were repeated. Assessments of caregivers and children were conducted by separate blinded raters. Caregivers were monitored by a psychiatrist at medication appointments and given referrals for further treatment at the end of the study. The study was registered at clinicaltrials.gov.

Statistical Analysis
The number of caregiver-reported, asthma-related hospitalizations, emergency room visits, and unscheduled clinic appointments by the child in the 12 months before the baseline assessment was recorded. Asthma-related hospitalizations, emergency room visits, and unscheduled clinic appointments by the child during caregiver antidepressant treatment were assessed at each visit by caregiver report. A per-month rate for hospitalizations, emergency room visits, and unscheduled clinic appointments was calculated for the 12 months before and during the antidepressant treatment. For other assessments, baseline-to-exit change (last observation carried forward) was used for the analyses. Data were analyzed by paired Student t-tests in all eight participants. Correlations between changes in outcome measures were examined by Pearson’s correlation coefficient. Significance was set at 0.05 for all analyses. Statistical analyses were performed with SPSS, Version 13.0.

RESULTS

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A total of 42 caregivers with current MDD were identified; 8 of these 42 otherwise-eligible caregivers elected to participate in the clinical trial. Reasons for declining to participate were not clear in most cases, but 9% reported scheduling problems, and 3% were incarcerated after the initial assessment. Caregivers who declined to participate (N=34) were similar to those who did participate (N=8) demographically except for caregiver relationship to child (25% fathers versus 0% fathers; Pearson’s chi-square p=0.009), and emergency room visits by the child in the past year (mean: 3.63; standard deviation [SD]: 2.50 versus 1.89 [1.23]; p=0.006). The participating caregivers consisted of six women and two men, with a mean age of 35.8 (6.6) years. The children were five boys and three girls, with a mean age of 9.8 (3.8) years. The race/ethnicity of caregivers and children were Caucasian (N=2), African-American (N=5), and Hispanic (N=1). Five caregivers and children had a household income of $25,000/year, and three had incomes of <$25,000. Antidepressant therapy and baseline assessments, including spirometry, were initiated at a mean of 34.5 (50.1) days after the child’s hospitalization.

All eight participating caregivers were started on escitalopram at 10 mg/day. One caregiver was switched to bupropion at 150 mg/day at Week 8 and titrated to 300 mg/day because of inadequate response to escitalopram (as per the algorithm). Two caregivers received lithium augmentation of escitalopram. One caregiver was a non-responder to paroxetine controlled-release at 25 mg/day at baseline. This person started escitalopram at baseline and was tapered off the paroxetine over 10 days. On the basis of pill counts, antidepressant adherence was 96%.

Table 1 shows baseline-to-exit changes on depression rating scales, asthma symptoms, and quality of life, as well as monthly rates of asthma-related service utilization during the 12 months before study entry and during antidepressant therapy. Caregiver mean scores on the QIDS–SR (caregiver self-rated depressive symptoms) decreased significantly, from 13.9 to 10.9 (p=0.03). Mean scores on the Ham–D (caregiver observer-rated depressive symptoms) showed a trend toward significant decrease, from 20.9 to 15.5 (p=0.08) during antidepressant therapy. Asthma symptom scores based on the PedAsthmaSS (asthma symptoms) correspondingly decreased significantly, from 19.4 to 13.3 (p=0.05). The rate of unscheduled clinic appointments for asthma showed a trend toward significant reduction, from 0.34/month to 0.14/month (p=0.07). PedAQoLQ (asthma-related quality of life), PedACaregiverQoLQ (caregiver quality of life), CDI–SF (child’s depressive symptoms) scores did not change significantly. Asthma-related hospitalizations and emergency room visits also did not change significantly, although the rate of emergency room visits was numerically lower, with a decrease from 0.30 ER visits/month to 0.16 ER visits/month (p=0.14). Two caregivers completed the entire 24-week study. Data from one of the completers are provided in Figure 1 to illustrate the correlation of baseline-to-exit change between Ham–D scores in the caregiver and peak expiratory flow in the child.

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TABLE 1. Caregiver Depressive Symptoms, Caregiver and Child Quality of Life, Child Asthma Symptoms, and Asthma-Related Service Utilization Before and During Antidepressant Treatment (N=8)

View larger version (48K): [in this window] [in a new window]

FIGURE 1.  Correlation of Baseline-to-Exit Change Between Ham–D Scores in the Caregiver and Peak Expiratory Flow in the Child

We saw significant correlations between improvement in caregiver depression scores and quality of life in the caregiver as well as objective measurement of asthma-related symptoms and lung functioning in the child (Table 2). Changes in QIDS–SR scores did not correlate significantly with changes in other outcome measures.

View this table: [in this window] [in a new window]

TABLE 2. Correlations Between Baseline-to-Exit Changes in Ham–D Scores and Changes on the PedACaregiverQoLQ, PedAsthmaSS, and Peak Expiratory Flow

DISCUSSION

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Depression is common in caregivers of children with asthma, and it appears to be associated with increased rates of unscheduled or emergency-care services for the child’s asthma.^4,5,7,8 In a recent report, we found an increased rate of unscheduled clinic visits in children of caregivers with current MDD.⁸

In this report, we examined the impact of antidepressant treatment on the caregiver’s depressive symptoms and on the child’s asthma. We found a significant reduction in self-rated depression, as assessed by the QIDS–SR, with a trend in the same direction on the observer-rated Ham–D, suggesting that the intervention was effective for depressive symptoms. The observed reduction in depressive symptoms, although modest, is likely of clinical significance. Early attrition probably decreased the impact of antidepressant therapy on depressive symptoms. Two of the participants did not return for a post-baseline assessment; thus, their baseline Ham–D and QIDS–SR scores were also used as exit scores.

Elevated rates of depression in children with asthma have been previously reported.¹⁷ In our sample, mean normative T-scores on the CDI–SF (child’s depressive symptom severity) were within the normal range and did not change significantly during the caregiver’s antidepressant therapy. However, a significant improvement on the PedAsthmaSS was observed, consistent with improvement in asthma symptoms during the trial. Also, rates of unscheduled clinic visits showed a trend toward a decrease during the antidepressant trial. The mechanism by which antidepressant treatment in the caregiver might be associated with improvement in the child’s asthma symptoms and service utilization patterns is not known. Improvement in the caregiver’s depression might lead to improvement in asthma through improvement in the child’s depressive symptoms. Weissman et al.¹⁸ reported that effective treatment in depressed mothers is associated with improvement in depression in their child. However, in our study, the children did not have elevated CDI–SF scores at baseline or a significant decrease in CDI–SF scores during the study. Treatment of caregiver depression could result in an improvement in treatment adherence for the child’s asthma. Psychological and family functioning are reported to influence treatment adherence in children with asthma.^19,20 The relationship between treatment of caregiver depression and treatment adherence by children has not, to our knowledge, been investigated. More speculatively, improvement in caregiver depression might also lead to lifestyle changes that decrease allergen exposure in the home.

Changes in Ham–D scores correlated significantly with changes in the PedACaregiverQoLQ, PedAsthmaSS, and peak flow. These findings suggest that improvement of depressive symptoms in the caregiver is associated with improvement in quality of life in the caregivers and as well as asthma in the child. It is noteworthy that the Ham–D was assessed by a different rater than the PedAsthmaSS and peak flow, and the child and caregiver raters were blind to each other’s findings.

A limitation of the pilot study is its small sample size. Larger studies are needed to confirm the preliminary findings. An additional limitation is that, given the design of the study, it is difficult to determine with certainty that antidepressant therapy in the caregiver was related to improvement in asthma in the child. Although a strong correlation was observed between changes in caregiver Ham–D scores and peak flow in the child, it is possible that improvement in the child’s asthma causes improvement in caregiver depression, rather than the reverse. It is also possible that the child’s asthma care during the hospitalization was responsible for the improvement in asthma symptoms. However, the baseline assessment for the antidepressant trial in the child was conducted at a mean of over 1 month after the hospitalization. Thus, the trial was not conducted during a period of aggressive asthma treatment.

In summary, the findings from this pilot study are promising in that they suggest that treatment of depression in caregivers of children with asthma is associated with improvement in the caregiver’s depressive symptoms and quality of life, but also improvement in the child’s asthma symptoms, lung functioning, and frequency of unscheduled clinic visits. Thus, the effective treatment of depression in the caregiver appears to be associated with a number of positive outcomes in both the caregiver and the child.

ACKNOWLEDGMENTS

 
The authors express appreciation to the staff of Children’s Medical Center of Dallas for assistance with the research project.

This research was supported by the Texas Higher Education Coordinating Board Minority Health Research and Education Grant Program.

REFERENCES

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Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Brown, E. S. Articles by Khan, D. A. Search for Related Content PubMed Citation Articles by Brown, E. S. Articles by Khan, D. A. Miscellaneous Childhood Disorders Depression

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