Psychotropic Treatment Pattern in Medicaid Pediatric Patients With Concomitant ADHD and ODD/CD

Abstract

Objective: To describe psychotropic treatment pattern and evaluate the association of socio-demographic factors and psychotropic combination therapy in children with ADHD and oppositional defiant disorder/conduct disorder (ODD/CD). Method: This is a cross-sectional drug utilization study based on Medicaid fee-for-service programs in 26 U.S. states (1999-2006). Children aged 4 to 18 with concomitant ADHD and ODD/CD were included. We calculated the prevalence of psychotropic drugs and used logistic regression to evaluate the role of socio-demographic factors in psychotropic combination therapy. Results: We identified 121,740 children with ADHD and ODD/CD (140,777 person-years). The period prevalence of “no psychotropic therapy,” psychotropic monotherapy, and psychotropic dual therapy was 38.1%, 44.7%, and 9.0%, respectively. The most common drug class was stimulants. Whites, males, and children in foster care were more likely to use psychotropic combination therapy. State-level variation was observed. Conclusion: “No psychotropic therapy” and stimulants dominate treatment choices in children with ADHD and ODD/CD. Socio-demographic characteristics are associated with combination psychotropic therapy.

Keywords

ADHD oppositional defiant disorder conduct disorder psychotropic drugs Medicaid

Introduction

ADHD affects about 1 out of 10 children in the United States and is a major contributor to the increased use of psychotropic drug in children (Centers for Disease Control and Prevention, 2010; Comer, Olfson, & Mojtabai, 2010). Children with ADHD are more likely to have psychiatric comorbidities than children without ADHD. Common psychiatric comorbidities in children with ADHD include oppositional defiant disorder (ODD), conduct disorder (CD), anxiety, bipolar disorder, depression, and substance abuse disorder (Kunwar, Dewan, & Faraone, 2007). Of these, ODD/CD is the most prevalent psychiatric comorbidity (40%-65%; Biederman et al., 2007; Connor, Steeber, & McBurnett, 2010). Despite its high prevalence, little evidence about appropriate psychotropic treatment exists for this patient population.

Current treatment recommendations for ADHD include medication therapy and/or behavioral therapy, both of which have been proven to be effective (Multimodal Treatment of ADHD [MTA], 1999a). At least half of children diagnosed with ADHD receive psychotropic medications based on parent report (Centers for Disease Control and Prevention, 2010). Medication management (stimulants, atomoxetine, and certain alpha agonists) is the first-line treatment for children aged 6 to 18. Medication management is the second-line treatment for children aged 4 to 5 after behavioral therapy (Subcommittee on Attention-Deficit/Hyperactivity Disorder et al., 2011).

The treatment for ODD/CD includes parent-management training programs, school-based programs, family therapy, or medication, based on the ODD guide for families by the American Academy of Child and Adolescent Psychiatry (Steiner, Remsing, & Work Group on Quality Issues, 2007). The treatment should begin with parent-management training and problem-solving skills training, and be highly individualized in which age and comorbidities are the most important factors to consider. Medication therapy should be used as an adjunct if no improvement is seen with parent-management training and problem-solving skills training (Steiner et al., 2007). Psychotropic medications may improve the oppositional behavior in the context of other principal diagnoses (e.g., stimulants in the context of ADHD). Mood stabilizers, antipsychotics, and stimulants may help control aggression in adolescents with CD. Only limited evidence shows selective serotonin reuptake inhibitors (SSRIs) are helpful for ODD in the context of mood disorders.

In children with concomitant ADHD and ODD/CD, the MTA (1999b) study in which 40% of the children had comorbid ODD showed combination therapy of stimulants and behavioral therapy benefited children with comorbid ODD most. Comorbid ODD/CD seemed not to modify the response to stimulants in treating ADHD (Abikoff et al., 2004; Jensen et al., 2001; Klein, Abikoff, Hechtman, & Weiss, 2004). Systematic, well-monitored titration of stimulant monotherapy (Blader, Pliszka, Jensen, Schooler, & Kafantaris, 2010), atomoxetine (Dittmann et al., 2011), bupropion (Riggs, Leon, Mikulich, & Pottle, 1998), lithium (Masi et al., 2009), alpha agonists (Connor, Findling, et al., 2010; Findling, McBurnett, White, & Youcha, 2014; Hirota, Schwartz, & Correll, 2014), atypical antipsychotics (Pringsheim & Gorman, 2012), the combination of stimulants and alpha agonists (Hirota et al., 2014), and the combination of stimulants with antipsychotics (Aman, Binder, & Turgay, 2004; Aman et al., 2014; Kronenberger et al., 2007) were also found to be effective in some trials of ADHD with ODD/CD. Antipsychotics have been proven efficacious for disruptive behavior in clinical trials, but antipsychotic monotherapy for ADHD is more costly and less effective than stimulants (Sikirica et al., 2012).

No guidelines integrate the abovementioned studies to standardize pharmacotherapeutic treatment for concomitant ADHD and ODD/CD. In addition, conflicting pharmacological and epidemiological evidence complicates treatment recommendations for children with ADHD and ODD/CD. First, clinical trials and post-marketing surveillance report aggressive behavior and hostility as side effects of ADHD drugs (US Food and Drug Administration [FDA], 2013), but two clinical trials suggest that stimulants reduced symptoms of both ADHD and ODD/CD (Sinzig et al., 2007; Spencer et al., 2006). Second, a post hoc analysis of two clinical trials in children with ADHD and disruptive behavior disorders showed the addition of risperidone to stimulants was superior in improving ODD symptoms when compared with stimulant only (Aman et al., 2004), but the efficacy and safety of combining stimulants and atypical antipsychotics remains controversial.

Outpatient prescribing of antipsychotics for children in the United States has increased almost fivefold between 1995 and 2002 (Cooper et al., 2006), and more than half of children on stimulants have been prescribed a concomitant antipsychotic at some point (Wonodi et al., 2007). The main concern of such combination is the potential pharmacological antagonism of these two classes of drugs, related to dopamine agonistic (stimulants) and dopamine antagonistic effect (antipsychotics). Some researchers speculate that affinity to different receptor types might alleviate the apparent antagonism. Overall, concomitant use of stimulants and antipsychotics should be cautious due to theoretical and empirical concerns, such as dyskinetic reactions (Yanofski, 2010).

To our knowledge, there are no drug utilization studies focusing on children with concomitant ADHD and ODD/CD. Therefore, we aimed to describe psychotropic pharmacotherapy in clinical practice for children with concomitant ADHD and ODD/CD and study demographic factors that might affect the initiation of combination psychotropic treatment.

Method

This is a cross-sectional drug utilization study based on Medicaid-fee-for-service programs in 26 U.S. states from 1999 to 2006. The overall pediatric population aged <18 covered by the programs reached 24 million during the 8-year study period. The study data set was established from the Medicaid Analytic eXtract Files (MAX), which includes monthly information on Medicaid eligibility and billing details for in- and outpatient services and prescription drugs, as well as patient demographic information.

Study Population

Patients who had at least two outpatient visit claims with diagnosis of ADHD (The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes: 314, 314.0, 314.00, 314.01, and 314.9) and ODD/CD (ICD-9-CM codes: 312-312.29, 312.4x-312.9x, 312.30, 312.34, 312.35, 313, 313.8, 313.81, and 313.9x) between January 1, 1999, and December 31, 2006, aged 4 to 18 years and eligible for Medicaid fee-for-service coverage were included in the study. Patients with any of the following psychiatric disorders in the study period were excluded from analysis: adjustment disorder (309-309.20, 309.22-309.80, 309.82-309.99, and 313.89); anxiety (300.0-300.09, 300.2-300.29, 300.3, 309.21, 309.81, 313.0, 313.2x, 308.0, 308.2x-308.9x); autism (299.0x, 299.8x, 299.9x); bipolar disorder (296.0-296.19, 296.4-296.81, 296.83-296.99, and 301.13); depression (296.2x, 296.3x, 296.82, 300.4, 311); eating/elimination/sleep disorders (307.1, 307.4x, 307.5x, 307.6-307.79, 347, 780.52-780.59, and 787.6); intellectual disabilities (317.xx, 318.xx, and 319.xx); learning, motor, and communication disorders (313.83, 315.xx, and 307.9); schizophrenia and other psychotic disorders (295.xx, 298.xx, and 297.xx); substance abuse (303.xx, 304.xx, and 305.xx); and tics/Tourette syndrome (307.2x and 307.3x).

Identification of Study Time

We defined the duration of ADHD and ODD/CD as from the first outpatient visit claim to the last. Overlapping periods of the two disorders ≥90 days were considered concomitant presence of ADHD and ODD/CD. We also conducted three sensitivity analyses in which the duration of ADHD and ODD/CD was defined as from every outpatient claim to 3 months, 6 months, and 1 year thereafter (see the online appendix).

Definition of Drug Exposure

We used pharmacy billing data to determine psychotropic drug exposure during the periods of concomitant ADHD and ODD/CD. The prescription fill date was set as the start day of treatment. The dispensed days’ supply with an extension of 10-day period was used to define treatment duration. We added an extension of 10-day period to compensate for small but irrelevant treatment breaks due to late refills. Days’ supply longer than 365 days was excluded. Psychotropic drugs were categorized into stimulants, atomoxetine, alpha agonists, antipsychotics, antidepressants, anticonvulsants, lithium, sedative/hypnotic, and anxiolytics. Concomitant therapy was defined based on the total number of days of overlap of different active ingredients. To distinguish between switching and concomitant therapy, we categorized exposure period with overlapped active ingredients shorter than 40 days as “undetermined.” The choice of 40 days as the cut-off point was based on the assumption that switching of antipsychotics in clinical practice is usually accomplished within 5 weeks (DMHMRSAS, 2005).

Data Analysis

We measured psychotropic drug utilization through summarizing the days of treatment regimen during the period of concomitant ADHD and ODD/CD for all eligible children. The analyses were based on person-time so one patient may contribute different amounts of person time to several drug exposure categories. In addition, we converted pharmacotherapeutic regimens on active ingredient level to class level and regroup the regimens to report class-level treatment pattern, for example, both methylphenidate + sertraline and methylphenidate + fluoxetine would be converted to stimulants + antidepressants so they could be combined. The combination of active ingredients in the same class will be downgraded; for example, methylphenidate + amphetamine would be downgraded from active ingredient–level dual therapy to class-level monotherapy, methylphenidate + amphetamine + sertraline would be downgraded from active ingredient–level triple therapy to class-level dual therapy.

We used logistic regression to evaluate the impact of state, gender, race, age, foster care, disability (supplemental security income, SSI), and poverty (temporary assistance for needy families, TANF) on the treatment of combination versus no combination psychotropic pharmacotherapy after controlling for the total length of follow-up. All analyses were completed with SAS 9.2 (Cary, NC).

The Institutional Review Board and Privacy Office at the University of Florida and the Centers for Medicare and Medicaid Services (CMS) approved this study.

Results

We identified 121,740 patients with a total of 140,777 person-years of concomitant ADHD and ODD/CD. The mean (±SD) and median length of concomitant ADHD and ODD/CD were 422 (±507) and 217 days, respectively. The mean (±SD) and median age at the first concomitant ADHD and ODD/CD period were 9.6 (±3.5) and 9.2 years, respectively (Table 1).

Table 1.

Demographic Characteristics of the Study Sample.

	n	%
Male	97,596	80.2
White	64,827	53.3
Black	43,242	35.5
Hispanic	7,957	6.5
Foster care	14,805	12.2
Disability	2,389	2.0
TANF	14,505	11.9
Age
<6	21,707	17.8
6-9	36,899	30.3
10-14	46,449	38.1
≥14	16,685	13.7

Note. TANF = temporary assistance for needy families.

Considering all included person-years with concomitant ADHD and ODD/CD, 38.1% did not have any psychotropic treatment, 44.7% had monotherapy, 9.0% dual therapy, 1.5% triple and more therapy, and 6.8% of time were considered uncertain because the overlap of drug–drug combination was shorter than 40 days. Tables 2 and 3 show psychotropic pharmacotherapy regimens on class level and active ingredient level, respectively. The most common psychotropic monotherapy was stimulants. The most common combination therapy regimens were based on stimulants, with alpha agonists or antipsychotics. The most common active ingredients included methylphenidate, amphetamine, atomoxetine, risperidone, and clonidine.

Table 2.

Class-Level Top Psychotropic Pharmacotherapy Regimens for ADHD and ODD/CD.

Monotherapy		Dual therapy (Top 5)		Triple therapy (Top 5)
Class	% (95% CI)	Class	% (95% CI)	Class	% (95% CI)
STI	33.5 [33.49, 33.53]	STI + AGN	2.89 [2.89, 2.90]	STI + AGN + APC	0.21 [0.21, 0.22]
APC	3.21 [3.20, 3.21]	STI + APC	2.04 [2.04, 2.05]	STI + ADP + APC	0.20 [0.20, 0.20]
ATO	2.65 [2.64, 2.66]	STI + ADP	1.69 [1.68, 1.69]	STI + ADP + APC	0.18 [0.18, 0.18]
AGN	2.22 [2.21, 2.22]	STI + ACV	0.65 [0.65, 0.65]	STI + APC + ACV	0.12 [0.12, 0.13]
ADP	2.12 [2.11, 2.12]	STI + ATO	0.36 [0.36, 0.37]	STI + AGN + ACV	0.10 [0.10, 0.10]
ACV	0.89 [0.88, 0.89]
AXL	0.26 [0.25, 0.26]
LIT	0.02 [0.02, 0.02]

Note. ODD = oppositional defiant disorder; CD = conduct disorder; CI = confidence interval; STI = stimulants; AGN = alpha agonist; APC = antipsychotics; ADP = antidepressants; ATO = atomoxetine; ACV = anticonvulsants; AXL = sedatives, hypnotics, and anxiolytics; LIT = lithium.

Table 3.

Active Ingredient–Level Top Psychotropic Pharmacotherapy Regimens for ADHD and ODD/CD.

Monotherapy		Dual therapy
Active ingredient	% (95% CI)	Active ingredient	% (95% CI)
MPH	17.72 [17.71, 17.74]	MPH + CLN	1.31 [1.31, 1.32]
AMP	13.94 [13.93, 13.96]	AMP + CLN	0.97 [0.96, 0.97]
ATO	2.65 [2.64, 2.66]	MPH + RIS	0.69 [0.68, 0.69]
RIS	2.19 [2.19, 2.20]	AMP + RIS	0.62 [0.62, 0.62]
CLN	1.65 [1.64, 1.65]	MPH + GUA	0.21 [0.21, 0.21]
dAMP	1.16 [1.16, 1.17]	MPH + ATO	0.20 [0.19, 0.20]
dMPH	0.57 [0.57, 0.57]	AMP + GUA	0.18 [0.18, 0.18]
BUP	0.56 [0.56, 0.57]	MPH + BUP	0.15 [0.15, 0.16]
GUA	0.56 [0.56, 0.57]	MPH + QUE	0.15 [0.15, 0.15]
ARI	0.39 [0.39, 0.40]	MPH + DVP	0.15 [0.15, 0.15]

Note. ODD = oppositional defiant disorder; CD = conduct disorder; CI = confidence interval; MPH = methylphenidate; CLN = clonidine; AMP = amphetamine; ATO = atomoxetine; RIS = risperidone; GUA = Guanfacine; dAMP = d-amphetamine; dMPH = dexmethylphenidate; BUP = bupropion; QUE = quetiapine; ARI = aripiprazole; DVP = divalproex.

We included 117,660 patients in the logistic regression to evaluate the impact of socio-demographic, geographic, and clinical factors on the decision of using more than one psychotropic drug versus one or no psychotropic treatment. We excluded 4,080 (3.4%) patients due to missing values for explanatory variables (e.g., foster care status). In the study population, 26,695 (22.1%) patients had at least one period longer than 40 days with combination psychotropic therapy. The p value of goodness-of-fit of the model was .9674. With the adjustment of the total follow-up, Whites, males, and those in foster care were more likely, whereas those with disability or receiving TANF were less likely, to be treated with more than one psychotropic drug. Compared with patients in Florida, patients in Iowa and Massachusetts were about twice more likely whereas patients in Idaho and West Virginia were about half less likely to be treated with more than one psychotropic drugs (Table 4).

Table 4.

Impact of Socio-Demographic, Geographic, and Clinical Factors on Treatment Decision of Using More Than One Psychotropic Drugs in Children With Concomitant ADHD and ODD/CD.

Socio-demographic/geographic/clinical factors		OR (95% CI)
Gender	Female vs. male	0.91 [0.87, 0.95]
Race/ethnicity	Black vs. White	0.46 [0.44, 0.48]
	Hispanic vs. White	0.50 [0.46, 0.53]
	Other vs. White	0.80 [0.75. 0.86]
Age (years)	6-9	Reference
	<6	1.05 [1.00. 1.10]
	10-14	0.93 [0.90, 0.96]
	≥14	0.92 [0.86, 0.97]
Length of follow-up	3-6 months	Reference
	<3 months	0.16 [0.14, 0.17]
	6 months-1 year	2.17 [2.04, 2.29]
	1 year-2 years	3.94 [3.72, 4.16]
	>2 years	8.53 [8.07, 9.01]
Foster care	Yes	1.60 [1.53, 1.67]
Disability	Yes	0.80 [0.71, 0.90]
TANF	Yes	0.83 [0.79, 0.87]
State	FL	Reference
	AR	0.87 [0.79, 0.97]
	GA	0.89 [0.81, 0.97]
	IA	2.11 [1.87, 2.39]
	ID	0.63 [0.52, 0.75]
	IL	0.71 [0.65, 1.77]
	IN	0.90 [0.81, 1.00]
	KS	1.18 [1.04, 1.34]
	LA	1.23 [1.11, 1.36]
	MA	1.69 [1.36, 2.10]
	MN	0.79 [0.70, 0.90]
	MO	0.90 [0.79, 1.02]
	MS	0.77 [0.69, 0.85]
	NC	0.89 [0.82, 0.96]
	NE	0.98 [0.84, 1.15]
	NH	1.17 [0.96, 1.42]
	NY	0.97 [0.88, 1.06]
	OH	1.00 [0.92, 1.09]
	PA	0.88 [0.80, 0.97]
	SC	0.85 [0.77, 0.94]
	TN	0.84 [0.76, 0.93]
	TX	1.34 [1.21, 1.48]
	VA	0.95 [0.79, 1.15]
	VT	0.74 [0.61, 0.89]
	WI	0.83 [0.74, 0.94]
	WV	0.64 [0.57, 0.71]

Note. ODD = oppositional defiant disorder; CD = conduct disorder; OR = odds ratio; CI = confidence interval; TANF = temporary assistance for needy families.

The three sensitivity analyses had similar results regarding treatment pattern and geographic variation (see the online appendix).

Discussion

We report four important findings involving psychotropic treatment pattern in children with concomitant ADHD and ODD/CD. First, in about 40% of the person-time of concomitant ADHD and ODD/CD there were no psychotropic drugs (re-)filled. Second, stimulants were the most common psychotropic drug class as monotherapy and the basis for combination therapy. Alpha agonists and antipsychotics were the most common psychotropic drugs used concomitantly with stimulants. Third, methylphenidate, clonidine, and risperidone were used more commonly than other agents in the same drug classes. Fourth, socio-demographic factors as well as geographic locations have impact on psychotropic treatment decision for children with ADHD and ODD/CD.

Although the efficacy and safety of psychotropic drugs for children aged >6 with ADHD are well established, the untreated proportion of time with ADHD and ODD/CD was as high as 40%. Untreated ADHD is associated with reduced self-esteem, social functioning, and poor academic achievements (Shaw et al., 2012). Untreated ODD/CD impairs children’s familial relations, lowers health-related quality of life (Klassen, Miller, & Fine, 2004), and increases the risk of developing substance abuse disorders (Molina & Pelham, 2003). ODD has also been suggested as an important determinant of poor medication adherence (Thiruchelvam, Charach, & Schachar, 2001). Several valid reasons for no pharmacotherapy of ADHD/ODD might exist, for example, mild disorder manifestation, treatment with behavioral therapy, or adverse events leading to discontinuation of treatment. Prospective studies showed that 30% of parents or families of children with ADHD with or without ODD/CD refused the recommendation of psychotropic treatment (Demidovich, Kolko, Bukstein, & Hart, 2011; Krain, Kendall, & Power, 2005). Thus, further studies should investigate the reasons to forego treatment of ADHD and ODD/CD.

We found that stimulants played the dominant role in psychotropic treatment of children with ADHD and ODD/CD not only as the major choice of monotherapy but also as the basis for combination therapy. This observation is consistent with the ODD guide for families by the American Academy of Child and Adolescent Psychiatry (Steiner et al., 2007), which recommends the treatment of oppositional behavior be considered in the context of other principal diagnoses. Stimulants are the first-line pharmacotherapy for ADHD, as well as ADHD with ODD/CD.

The top two psychotropic combination therapies were stimulants with alpha agonists and stimulants with antipsychotics. The efficacy and safety of stimulants with alpha agonists have been established in clinical trials of the treatment of ADHD (Hirota et al., 2014). The combination of stimulants and antipsychotics was supported by a recent clinical trial “Treatment of Severe Childhood Aggression” (TOSCA study) to some extent, in which risperidone provided moderate but variable improvement in aggressive and other seriously disruptive child behavior when added to parent training and optimized stimulant treatment (Aman et al., 2014). Adverse drug effects should be considered when using combination therapy, such as fatigue, somnolence/sedation hypotension, bradycardia, and possibly QTc prolongation with alpha agonists-containing regimens (Hirota et al., 2014) and extrapyramidal symptoms (EPS), weight gain, and hyperprolactinemia with antipsychotics-containing regimens (Linton, Barr, Honer, & Procyshyn, 2013). In addition, it seems that the speculated theory that stimulants may reduce metabolic adverse effects of antipsychotics does not exist (Linton et al., 2013). Therefore, physicians should be cautious to prescribe alpha agonists or antipsychotics with stimulants and monitor adverse drug events closely if combination therapy is used.

The fact that methylphenidate was used more often than amphetamine in children with ADHD has been reported in multiple drug utilization studies (Castle, Aubert, Verbrugge, Khalid, & Epstein, 2007; Christensen, Sasane, Hodgkins, Harley, & Tetali, 2010; Lawson, Johnsrud, Hodgkins, Sasane, & Crismon, 2012). Despite the suggestion that amphetamine might be better in the presence of ODD/CD with ADHD (Arnold, 2000), our study indicates that clinical practice does not follow this suggestion. No drug utilization studies are available to compare the use of clonidine and guanfacine in children with ADHD in clinical practice. One possible explanation for the fact that clonidine was used more often than guanfacine is that the evidence and studies are more for clonidine than guanfacine for children with inattention, hyperactivity, and impulsiveness (Scahill, 2009). Similarly, the most commonly used antipsychotic, risperidone, has more studies to support its efficacy and safety in children with ADHD and disruptive disorders than other antipsychotics (Loy, Merry, Hetrick, & Stasiak, 2012; Maher & Theodore, 2012; Pringsheim & Gorman, 2012). However, the preference of specific active ingredients in a drug class should be interpreted with caution. As the study time frame is 1999 to 2006, drugs introduced to the market during this time period (e.g., atomoxetine, 2003; aripiprazole, 2002) by design were used less than drugs introduced to the market before 1999. Therefore, further studies to reflect the dynamic psychotropic drug selection across years are needed to evaluate physician preference.

In the regression model, we found both clinical and non-clinical factors were associated with using psychotropic drug–drug combinations. Besides demographic and clinical factors, we found state of residence had an impact on the decision of psychotropic combination pharmacotherapy. Geographic variation in psychotropic treatment decisions in children has been found in previous studies (Raghavan, Lama, Kohl, & Hamilton, 2010) and may be attributable to differences in the understanding and belief of the role of pharmacotherapy among clinicians, the availability of local expertise, or reimbursement policies and formulary management strategies. Patient factors, such as quality of life, socio-economic status, education, or cultural beliefs, also contribute to the variation. The geographic variations deserve further investigation to ensure consistent and evidence-based patient care.

Our study has three unique strengths. First, to our knowledge, this is the first large drug utilization study targeting children with concomitant ADHD and ODD/CD. The study deepens our understanding of psychotropic treatment in this unique patient population. Second, we used 8-year Medicaid fee-for-service data in 26 U.S. states. The long study time and large number of states make the study generalizable to Medicaid pediatric population. Third, we established a tight temporal link between the diagnosis of ADHD and ODD/CD and psychotropic drug use, allowing inferences about disorder-specific treatment regimen. Finally, the exclusion of other common disorders allowed focus on ADHD and ODD/CD.

Our study also has limitations. First, the time frame of this study is 1999-2006; therefore, the results in this study may not be generalizable to current practice. The practice may have changed along with the introduction of new psychotropic drugs. However, this study has its unique value that it provides baseline to describe practice change once new data are available. The second limitation of this study is that dispensing data represent filled prescriptions but do not allow direct inferences whether drugs were indeed administered, and thus, periods of non-compliance might be underestimated.

Conclusion

“No psychotropic therapy” and psychotropic monotherapy dominated the time with concomitant ADHD and ODD/CD in children and adolescents. Stimulants serve as the predominant monotherapy regimen and the basis for combination therapy. Alpha agonists and antipsychotics were the other two most commonly used psychotropic drug classes. Socio-demographic characteristics and state residency affect treatment decisions regarding combination psychotropic treatment for children with concomitant ADHD and ODD/CD.

Footnotes

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Bussing has served as consultant to Shire and received travel support from Medici and Janssen.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded in part by Grant R01-HS0185606 from the Agency of Healthcare Research and Quality (AHRQ). Ms. Liu was funded by the Du Bow Fellowship for Graduate Education at the University of Florida. Dr. Bussing has received research funding from NIMH AHRQ, Pfizer, and Otsuka.

Author Biographies

Xinyue Liu, BS. Pharm, is PhD candidate majoring in pharmacoepidemiology in the department of pharmaceutical outcomes and policy, college of pharmacy, University of Florida. She is interested in drug safety, pediatrics, psychiatry and neurology.

Vaishali Shah, PharmD, was a PharmD student in the college of pharmacy, University of Florida when the work in this manuscript was done. Recently she completed a PGY-1 pharmacy residency with a focus in ambulatory care at the Stratton VA Medical Center in Albany, NY. She is currently working at Mercy Hospital in Chicago, IL as an Ambulatory Care Clinical Specialist.

Paul Kubilis, MS, is a Statistician in the college of medicine, University of Florida. He is specialized in database study and model building.

Dandan Xu, MS, is a Statistician in the college of pharmacy, University of Florida. She is specialized in database and electronic health records study.

Regina Bussing, MD, is a Tenured Professor and the interim chair of the department of psychiatry, college of medicine, University of Florida. She is specialized in pediatrics and psychiatry.

Almut G. Winterstein, PhD, is a Tenured Professor and the Interim Chair of the department of pharmaceutical outcomes and policy, college of medicine, University of Florida. She is specialized in pharmacoepidemiology.

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