BACKGROUND AND OBJECTIVES

Migraine headache is a common disorder in pediatrics, sometimes leading to hospital admission. Psychiatric comorbidities are prevalent in adults with migraine headache, but there is limited evidence in the pediatric population. This study aimed to examine the prevalence of psychiatric comorbidity in children hospitalized for migraine headache and assess the association of this comorbid state on treatment interventions and outcomes.

METHODS

This multicenter, retrospective cohort study examined data from the Pediatric Health Information System. Subjects included patients aged 6 to 18 hospitalized for migraine headache between 2010 and 2018, excluding those with complex chronic conditions. Associations of psychiatric comorbidity with treatments, length of stay (LOS), cost, and 30-day readmissions were assessed using the Fisher-exact, Wilcoxon-rank-sum test, and adjusted linear or logistic regression models.

RESULTS

The total 21 436 subjects included 6796 (32%) with psychiatric comorbidity, with prevalence highest for anxiety (2415; 11.2%), depression (1433; 6.7%), and attention-deficit/hyperactivity disorder (1411; 6.5%). Patients with psychiatric comorbidity were significantly more likely (P < .001) to receive dihydroergotamine (61% vs 54%), topiramate (23% vs 18%), and valproate (38% vs 34%), and have longer mean LOS (2.6 vs 2.0 days), higher average costs ($8749 vs $7040), and higher 30-day readmission (21% vs 17%).

CONCLUSIONS

Of children hospitalized for migraine headache, 32% have comorbid psychiatric disorders associated with increased use of medications, longer LOS, and increased cost of hospitalization and readmission. Prospective studies are recommended to identify optimal multidisciplinary care models for children with migraine headaches and psychiatric comorbidities in the inpatient setting.

Headache is a commonly reported symptom in childhood, with migraine headache representing a frequently noted recurrent form. The prevalence of migraine headache in the pediatric population ranges from 3.3% to 21.4%, with rates increasing throughout childhood into adolescence.1  The pain caused by recurrent headaches in childhood can be as disabling as that experienced in other chronic conditions,2  leading to lower quality of life and poorer school attendance.3 

Children experiencing a migraine that cannot be managed with oral medications may require hospital admission for effective treatment. Inpatient migraine headache treatment typically involves a poly-pharmaceutical approach, including intravenous fluids, antiemetics, nonsteroidal anti-inflammatory drugs, steroids, and anticonvulsant medications.4  Intractable migraine headache may require more aggressive therapy, such as dihydroergotamine (DHE) or peripheral nerve or sphenopalatine ganglion blocks.4 

Psychiatric conditions have become more prevalent in the general pediatric population, with recent estimates at 3.2% for depression, 7.1% for anxiety, and 8.4% for attention-deficit/hyperactivity disorder (ADHD).5,6  The impact of these psychiatric disorders extends beyond that of their primary effect, confounding treatment of comorbid conditions such as migraines.7  Studies in outpatient settings have suggested an association between psychiatric conditions and migraine headache in children.8,9  However, in pediatric patients hospitalized for migraine headache, there is limited evidence regarding psychiatric comorbidities prevalence and impact on clinical course and treatment efficacy.

The objective of this study is to examine the association between psychiatric comorbidities and treatment interventions, as well as hospital outcomes, among children hospitalized for treatment of migraine headache.

This multicenter, retrospective cohort study examined data from the Pediatric Health Information System (PHIS), an administrative database of 51 freestanding pediatric hospitals in the United States affiliated with the Children’s Hospital Association (Lenexa, KS), and was approved by the investigator’s site institutional review board.

Children aged 6 to 18 hospitalized (inpatient or observation status) with a principal discharge diagnosis of migraine headache between January 1, 2010, and June 30, 2018, were included. A migraine headache diagnosis was defined according to the International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes. For each patient, the top 2 secondary psychiatric diagnoses were identified according to a PHIS-established list of International Classification of Diseases, 9th revision, and International Classification of Diseases, 10th revision Clinical Modification codes associated with psychiatric diagnoses.10  Patients were excluded if diagnosed with a complex chronic condition according to PHIS criteria.11 

For de-identification purposes, patients were assigned a unique encrypted patient code to allow tracking across visits. Patient data retrieved included presence and type of psychiatric comorbid condition(s), demographics (age, gender, race, and ethnicity), medications, and outcomes (length of stay [LOS], readmission within 7 and 30 days, and cost). Costs were estimated through charges using hospital and year-specific cost-to-charge ratios.12 

Patients were categorized into 2 groups according to the presence or absence of any psychiatric comorbidity. The yearly rate of psychiatric comorbidities was compared over the study period using the Cochran-Armitage trend test. The distribution of demographics, interventions, and outcomes was summarized within each group of patients, with and without psychiatric comorbidity and compared among groups using the Fisher’s exact or Wilcoxon rank sum test as appropriate for the data distribution. The magnitude of association between psychiatric comorbidity and outcomes was estimated as the difference in means or odds ratio, along with corresponding 95% confidence intervals to indicate variability. For each outcome, possible confounding by demographics associated with psychiatric comorbidity was assessed with multivariable linear and logistic regression models. As the distribution of LOS and cost was right-tailed, the natural logarithm transformation was applied to better approximate a Gaussian distribution for linear regression models. Statistical analyses were performed using the software package SAS (SAS Institute, Cary, NC), and all statistical tests were 2-sided, with significance evaluated at the 5% level.

During the study period, 21 436 patients meeting criteria were hospitalized. The mean age was 13.6 years, and a majority of patients were female (15 419 [72%]), who self-identified as White (16 141 [75%]) and non-Hispanic (17 483 [87%]). The prevalence of psychiatric comorbidities increased significantly, from 22% in 2010 to a high of 39% in 2017 (Table 1). Psychiatric comorbidities were present in 6796 (32%) patients, with 4612 (68%) patients diagnosed with 1 or more of the 3 top diagnoses: anxiety (2415; prevalence 11.2%), depression (1433; prevalence 6.7%), and ADHD (1411; prevalence 6.5%). The remaining 2184 patients (32%) were diagnosed with 1 or more of 250 other psychiatric conditions, each with a prevalence of <1%.

TABLE 1

Association of Psychiatric Comorbidity with Demographics and Treatments Among Pediatric Inpatients Hospitalized with Migraine Headache

FactorTotal N = 21 436Psychiatric ComorbiditiesPa
Present (N = 6796)Absent (N = 14 640)
Year, n (%)b    <.001 
 2010 1659 (8) 369 (22) 1290 (78)  
 2011 1859 (9) 482 (26) 1377 (74)  
 2012 2482 (11) 665 (27) 1817 (73)  
 2013 2492 (12) 722 (29) 1770 (71)  
 2014 2653 (12) 858 (32) 1795 (68)  
 2015 2840 (13) 932 (33) 1908 (67)  
 2016 2923 (14) 1035 (35) 1888 (65)  
 2017 3081 (14) 1193 (39) 1888 (61)  
 2018 1447 (7) 540 (37) 907 (63)  
Age at admission, y    <.001 
 Mean (SD) 13.6 (3.0) 14 (2.8) 13.4 (3.0)  
 Median (IQR) 14 (12–16) 15 (12–16) 14 (11–16)  
Age, y, n (%)    <.001 
 6–12 6861 (32) 1865 (27) 4996 (34)  
 13–15 8118 (38) 2585 (38) 5533 (38)  
 16–18 6457 (30) 2346 (35) 4111(28)  
Gender, n (%)    .02 
 Male 6017 (28) 1981 (29) 4036 (28)  
 Female 15419 (72) 4815 (71) 10604 (72)  
Hispanic ethnicity, n (%) (missing, n = 1314) 2639 (13) 811 (13) 1828 (13) .27 
Race, n (%)     
 American Indian 64 (0.3) 13 (0.2) 51 (0.4) .06 
 Asian American 218 (1) 54 (0.8) 164 (1) .03 
 Black 2862 (13) 753 (11) 2109 (15) <.001 
 White 16 141 (75) 5287 (78) 10 854 (74) <.001 
Acute headache medications, n (%)     
 Acetaminophen 4751 (22) 1603 (24) 3148 (22) .001 
 Ibuprofen 3172 (15) 980 (14) 2192 (15) .29 
 Ketorolac 14 405 (67) 4640 (68) 9765 (67) .02 
 DHE 11 968 (56) 4130 (61) 87 834 (54) <.001 
 Morphine 1407 (7) 463 (7) 944 (6) .31 
 Magnesium 4535 (21) 1586 (23) 2949 (20) <.001 
Preventative medications, n (%)     
 Topiramate 4193 (20) 1539 (23) 2654 (18) <.001 
 Valproate 7512 (35) 2571 (38) 4941 (34) <.001 
Steroids, n (%)     
 Dexamethasone 1811 (8) 642 (9) 1169 (8) .001 
 Methyl prednisone 2844 (13) 988 (15) 19 856 (13) .002 
FactorTotal N = 21 436Psychiatric ComorbiditiesPa
Present (N = 6796)Absent (N = 14 640)
Year, n (%)b    <.001 
 2010 1659 (8) 369 (22) 1290 (78)  
 2011 1859 (9) 482 (26) 1377 (74)  
 2012 2482 (11) 665 (27) 1817 (73)  
 2013 2492 (12) 722 (29) 1770 (71)  
 2014 2653 (12) 858 (32) 1795 (68)  
 2015 2840 (13) 932 (33) 1908 (67)  
 2016 2923 (14) 1035 (35) 1888 (65)  
 2017 3081 (14) 1193 (39) 1888 (61)  
 2018 1447 (7) 540 (37) 907 (63)  
Age at admission, y    <.001 
 Mean (SD) 13.6 (3.0) 14 (2.8) 13.4 (3.0)  
 Median (IQR) 14 (12–16) 15 (12–16) 14 (11–16)  
Age, y, n (%)    <.001 
 6–12 6861 (32) 1865 (27) 4996 (34)  
 13–15 8118 (38) 2585 (38) 5533 (38)  
 16–18 6457 (30) 2346 (35) 4111(28)  
Gender, n (%)    .02 
 Male 6017 (28) 1981 (29) 4036 (28)  
 Female 15419 (72) 4815 (71) 10604 (72)  
Hispanic ethnicity, n (%) (missing, n = 1314) 2639 (13) 811 (13) 1828 (13) .27 
Race, n (%)     
 American Indian 64 (0.3) 13 (0.2) 51 (0.4) .06 
 Asian American 218 (1) 54 (0.8) 164 (1) .03 
 Black 2862 (13) 753 (11) 2109 (15) <.001 
 White 16 141 (75) 5287 (78) 10 854 (74) <.001 
Acute headache medications, n (%)     
 Acetaminophen 4751 (22) 1603 (24) 3148 (22) .001 
 Ibuprofen 3172 (15) 980 (14) 2192 (15) .29 
 Ketorolac 14 405 (67) 4640 (68) 9765 (67) .02 
 DHE 11 968 (56) 4130 (61) 87 834 (54) <.001 
 Morphine 1407 (7) 463 (7) 944 (6) .31 
 Magnesium 4535 (21) 1586 (23) 2949 (20) <.001 
Preventative medications, n (%)     
 Topiramate 4193 (20) 1539 (23) 2654 (18) <.001 
 Valproate 7512 (35) 2571 (38) 4941 (34) <.001 
Steroids, n (%)     
 Dexamethasone 1811 (8) 642 (9) 1169 (8) .001 
 Methyl prednisone 2844 (13) 988 (15) 19 856 (13) .002 

IQR, interquartile range.

a

P value from the Cochran-Armitage trend test for year, the Wilcoxon rank sum test for quantitative measures, or Fisher exact test for categorical variables.

b

To identify time trend, the percentage of subjects with and without psychiatric comorbidities is reported using year total as denominator.

Patients with any psychiatric comorbidities were on average 1 year older and more likely to identify as White (Table 1).

Patients with versus without psychiatric comorbidities were significantly more likely to receive treatment with most medications investigated (Table 1), notably with DHE (61% vs 54%), topiramate (23% vs 18%), and valproate (38% vs 34%).

The mean LOS was significantly longer for patients with versus without psychiatric comorbidities (2.6 days vs 2.0 days). Consistent with longer LOS, average cost was significantly higher for patients with psychiatric comorbidities versus those without ($8749 vs $7040). Readmission rates within 7 and 30 days were also significantly higher among patients with versus without psychiatric comorbidities (10% vs 8% and 21% vs 17%, respectively) (Table 2). Confounding by demographics was not detected for any of the outcomes.

TABLE 2

Association of Psychiatric Comorbidity with Outcomes Among Pediatric Inpatients Hospitalized with Migraine Headache

FactorTotal (N = 21 436)Psychiatric ComorbiditiesPaMean Difference or OR (95% CI)
Present (n = 6796)Absent (n = 14 640)
LOS (days)    <.001 0.55 (0.50–0.61) 
 Mean (SD) 2.19 (1.75) 2.56 (2.08) 2.01 (1.54)   
 Median (IQR) 2.0 (1.0–3.0) 2.0 (1.0–3.0) 2.0 (1.0–2.0)   
Cost, US dollars    <.001 1710 (1327–2093) 
 Mean (SD) 7582 (12 725) 8750 (13 811) 7040 (12 151)   
 Median (IQR) 5061 (3251–8269) 5851 (37 418–9756) 4761 (3059–7683)   
Readmission, n (%)    <.001 1.29 (1.20–1.39) 
 None 17 511 (82) 5369 (79) 12 142 (83)   
 ≤30 d 3925 (18) 1427 (21) 2498 (17)   
Readmission, n (%)    <.001 1.26 (1.14–1.40) 
 None 17511 (91) 5369 (90) 12 142 (92)   
 ≤7 d 1647 (10) 590 (10) 1057 (8)   
FactorTotal (N = 21 436)Psychiatric ComorbiditiesPaMean Difference or OR (95% CI)
Present (n = 6796)Absent (n = 14 640)
LOS (days)    <.001 0.55 (0.50–0.61) 
 Mean (SD) 2.19 (1.75) 2.56 (2.08) 2.01 (1.54)   
 Median (IQR) 2.0 (1.0–3.0) 2.0 (1.0–3.0) 2.0 (1.0–2.0)   
Cost, US dollars    <.001 1710 (1327–2093) 
 Mean (SD) 7582 (12 725) 8750 (13 811) 7040 (12 151)   
 Median (IQR) 5061 (3251–8269) 5851 (37 418–9756) 4761 (3059–7683)   
Readmission, n (%)    <.001 1.29 (1.20–1.39) 
 None 17 511 (82) 5369 (79) 12 142 (83)   
 ≤30 d 3925 (18) 1427 (21) 2498 (17)   
Readmission, n (%)    <.001 1.26 (1.14–1.40) 
 None 17511 (91) 5369 (90) 12 142 (92)   
 ≤7 d 1647 (10) 590 (10) 1057 (8)   

CI, confidence interval; IQR, interquartile range; OR, odds ratio.

a

P value from Wilcoxon rank sum test for quantitative measures, or Fisher exact test for categorical variable.

This large cohort study demonstrates that 32% of pediatric patients hospitalized with migraine headache are diagnosed with 1 or more psychiatric conditions. The most common comorbid diagnoses identified in our population were anxiety, depression, and ADHD, with the estimated prevalence of each well above that reported in the general population. Furthermore, associations were identified between the presence of psychiatric comorbidities and increased medication administration, LOS, cost, and readmissions for children hospitalized for migraine.

The association between psychiatric disorders and migraine headache has been well documented in adult patients,13,14  and recent outpatient studies in children have also suggested a correlation.8,9,15,16  Our study estimated a high rate of psychiatric disorders among pediatric patients hospitalized for migraine, aligning with recent outpatient studies reporting psychiatric comorbidity in 40% to 56% of children with migraine headache.8,9  Additionally, anxiety, depression, and ADHD were the most prevalent psychiatric comorbidities in our hospitalized population, which is consistent with previous reports.5,6 

Our study demonstrates that patients hospitalized for migraine headache with a psychiatric comorbidity have increased use of most medications, both for immediate headache abortion and headache prophylaxis, and also require increased use of agents usually reserved for treatment of severe, intractable migraine (eg, DHE). It is unclear why patients with psychiatric comorbidity require increased medication use for migraine management; however, this factor may have contributed to the longer LOS and higher cost of hospitalization seen in this population. Studies of adult outpatients have shown that, if left untreated, comorbid psychiatric conditions can increase migraine-related disability, reduce quality of life, and negatively impact treatment outcomes.13,17  Although it is possible that untreated psychiatric conditions in the pediatric migraine headache patients in our study influenced the increased medication use and poor outcomes identified, further study is needed to clarify.

For all patients with migraine headaches, it has been suggested that inpatient migraine treatment requires a biopsychosocial and multidisciplinary approach.18  A meta-analysis of 35 randomized controlled trials concerning the use of nonpharmacologic pain management methods in children with migraine and tension-type headache have confirmed their efficacy in the outpatient setting.19  We postulate that the impact of this multimodal, multidisciplinary treatment approach for children with both migraines and psychiatric conditions may be even greater. It has also been suggested that incorporation of treatment of known psychiatric disorders into the overall management of children with migraine may facilitate modification of the trajectories of both conditions across their lifespan.20  Future studies are needed to evaluate the clinical impact of treated versus untreated psychiatric comorbidity and to explore the feasibility and effectiveness of a multidisciplinary treatment model for children with a psychiatric disorder who are hospitalized for the treatment of migraine headache.

This retrospective analysis of a multisite billing database is subject to issues of data quality, including potentially incomplete and inaccurate information. Inaccurate documentation of comorbid diagnoses may have led to false classification of patients into the wrong study group. Unavailable data on treatment of psychiatric comorbidities and duration of each migraine treatment limit the ability to tease out factors contributing to higher LOS and cost. Possible confounding bias was checked using appropriate multivariable models. In addition, the data source is limited to those tertiary care children’s hospitals that contributed data to PHIS and may not be reflective of all children treated for migraine headache in a hospital setting.

Psychiatric comorbidities are prevalent in 32% of pediatric patients hospitalized for treatment of migraine headache. These comorbid states are statistically associated with increased use of therapies, longer LOS, increased cost, and increased readmission. Prospective studies are recommended to confirm clinical relevance and identify optimal multidisciplinary care models that comprehensively address both neurologic and psychiatric conditions for pediatric migraine patients with psychiatric comorbidities in the inpatient setting.

FUNDING: No external funding.

CONFLICT OF INTEREST DISCLOSURE: The authors have indicated they have no potential conflicts of interest to disclose.

Dr Kafle conceptualized and designed the study, collected the data, conducted initial data analyses, drafted the initial manuscript, and reviewed and revised the manuscript; Dr Mirea conducted the data analyses and reviewed and revised the manuscript; Dr Gage conceptualized and designed the study, supervised data collection, and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

1
Abu-Arafeh
I
,
Razak
S
,
Sivaraman
B
,
Graham
C
.
Prevalence of headache and migraine in children and adolescents: a systematic review of population-based studies
.
Dev Med Child Neurol
.
2010
;
52
(
12
):
1088
1097
2
Powers
SW
,
Patton
SR
,
Hommel
KA
,
Hershey
AD
.
Quality of life in childhood migraines: clinical impact and comparison to other chronic illnesses
.
Available at: www.pediatrics.org/cgi/content/full/112/1/e1. Accessed January, 12, 2022
3
El-Heneedy
YAE
,
Bahnasy
WS
,
ELAhwal
SA
,
Amer
RAR
,
Abohammar
SDA
,
Salem
HAM
.
Psychiatric and sleep abnormalities in school-age children with migraine
.
Egypt J Neurol Psychiat Neurosurg
.
2019
;
55
(
16
)
4
Rastogi
RG
,
Borrero-Mejias
C
,
Hickman
C
,
Lewis
KS
,
Little
R
.
Management of episodic migraine in children and adolescents: a practical approach
.
Curr Neurol Neurosci Rep
.
2018
;
18
(
12
):
103
5
Ghandour
RM
,
Sherman
LJ
,
Vladutiu
CJ
et al
.
Prevalence and treatment of depression, anxiety, and conduct problems in us children
.
J Pediatr
.
2019
;
206
:
256
267.e3
6
Danielson
ML
,
Bitsko
RH
,
Ghandour
RM
,
Holbrook
JR
,
Kogan
MD
,
Blumberg
SJ
.
Prevalence of parent-reported ADHD diagnosis and associated treatment among US children and adolescents, 2016
.
J Clin Child Adolesc Psychol
.
2018
;
47
(
2
):
199
212
7
Bellini
B
,
Arruda
M
,
Cescut
A
et al
.
Headache and comorbidity in children and adolescents
.
J Headache Pain
.
2013
;
14
(
1
):
79
8
Öztop
DB
,
Taşdelen
BI
,
PoyrazoğLu
HG
et al
.
Assessment of psychopathology and quality of life in children and adolescents with migraine
.
J Child Neurol
.
2016
;
31
(
7
):
837
842
9
Kandemir
G
,
Hesapcioglu
ST
,
Kurt
ANC
.
What are the psychosocial factors associated with migraine in the child? Comorbid psychiatric disorders, family functioning, parenting style, or mom’s psychiatric symptoms?
J Child Neurol
.
2018
;
33
(
2
):
174
181
10
Zima
BT
,
Rodean
J
,
Hall
M
,
Bardach
NS
,
Coker
TR
,
Berry
JG
.
Psychiatric disorders and trends in resource use in pediatric hospitals
.
Pediatrics
.
2016
;
138
(
5
):
e20160909
11
Feudtner
C
,
Feinstein
JA
,
Zhong
W
,
Hall
M
,
Dai
D
.
Pediatric complex chronic conditions classification system version 2: updated for ICD-10 and complex medical technology dependence and transplantation
.
BMC Pediatr
.
2014
;
14
:
199
12
Agency for Healthcare Research and Quality; Healthcare Cost and Utilization Project (HCUP)
.
Cost-to-charge ratio files
.
Available at: www.hcup-us.ahrq.gov/db/ccr/costtocharge.jsp. 2020. Accessed September 1, 2020
13
Dresler
T
,
Caratozzolo
S
,
Guldolf
K
et al
.
European Headache Federation School of Advanced Studies (EHF-SAS)
.
Understanding the nature of psychiatric comorbidity in migraine: a systematic review focused on interactions and treatment implications
.
J Headache Pain
.
2019
;
20
(
1
):
51
14
Breslau
N
.
Psychiatric comorbidity in migraine
.
Cephalalgia
.
1998
;
18
Suppl 22
:
56
58
,
discussion 58–61
15
Qubty
W
,
Gelfand
AA
.
Psychological and behavioral issues in the management of migraine in children and adolescents
.
Curr Pain Headache Rep
.
2016
;
20
(
12
):
69
16
Gelfand
AA
.
Psychiatric comorbidity and paediatric migraine: examining the evidence
.
Curr Opin Neurol
.
2015
;
28
(
3
):
261
264
17
Jeyagurunathan
A
,
Abdin
E
,
Vaingankar
JA
et al
.
Prevalence and comorbidity of migraine headache: results from the Singapore Mental Health Study 2016
.
Soc Psychiatry Psychiatr Epidemiol
.
2020
;
55
(
1
):
33
43
18
Slover
R
,
Kent
S
.
Pediatric Headaches
.
Adv Pediatr
.
2015
;
62
(
1
):
283
293
19
Fisher
E
,
Heathcote
L
,
Palermo
TM
,
de C Williams
AC
,
Lau
J
,
Eccleston
C
.
Systematic review and meta-analysis of psychological therapies for children with chronic pain
.
J Pediatr Psychol
.
2014
;
39
(
8
):
763
782 n
20
Lateef
T
,
He
JP
,
Nelson
K
et al
.
Physical-mental comorbidity of pediatric migraine in the Philadelphia neurodevelopmental cohort
.
J Pediatr
.
2019
;
205
:
210
217