Early Diagnoses and Psychotherapeutic Medication Treatment Experiences of a Cohort of Children Under 6 Years Old Who Received Antipsychotic Treatment in Florida's Medicaid Program

Abstract

Objective:

To describe the diagnostic characteristics and psychotherapeutic medication experiences of a cohort of children who received antipsychotic treatment before their sixth birthday.

Methods:

Children enrolled in Florida's Medicaid program were identified as having initiated an index episode of antipsychotic treatment before their sixth birthday. The characteristics of these children were compared to nonrecipients who were less than 6 years old on January 1, 2004. An index episode is described as the filling of at least two consecutive antipsychotic prescriptions with a gap no greater than 15 days between the last day supplied of the first prescription and the fill date of the second prescription. We describe the diagnoses and psychotherapeutic medication experiences of these children during the 365 days before the start of their index episodes (preindex periods) and during the 365 days immediately after the start of their index episodes (index periods).

Results:

Five hundred twenty-eight recipients were identified. Recipients were more likely than nonrecipients to be male, to be older, and to have a supplemental security income enrollment status. Recipients were exposed to psychotherapeutic medications at very early ages. Four hundred thirty-nine (83%) had already been treated with some psychotherapeutic medication during their preindex periods. Of these children, 303 (69%) filled at least one prescription for an antipsychotic medication. Index antipsychotic episodes were often lengthy. Mean ± standard deviation and median episode lengths were 266.9 ± 286.8 and 174 days, respectively. During the index periods half of the children were found to have attention-deficit/hyperactivity disorder and 18% had disruptive behavior disorders. Treatment during these periods included other classes of psychotherapeutic medications for 73% of children. Nearly 30% (29.6%) received two or more classes of medications in addition to antipsychotics.

Conclusions:

We found a large group of very young children who were persistently treated with antipsychotic medications. This early and extensive exposure is a cause for concern.

Introduction

A ntipsychotic utilization among children and adolescents has increased markedly in the United States and Europe since the mid-1990s (Cooper et al. 2004; Patel et al. 2005; Olfson et al. 2006; Kalverdijk et al. 2008; Vitiello et al. 2009). In the United States the rate of increase in utilization among children and adolescents has recently exceeded that of adults. Specifically, the percentage of all antipsychotic recipients accounted for by youth increased from 7% in 1996–1997 to 15% in 2005 (Domino and Swartz 2008).Very young children have participated in this trend. Zito and colleagues (2007) reported a fivefold increase in antipsychotic prevalence in children 0–4 years old in two Medicaid programs from 1995 to 2001. Patel and colleagues (2002) observed a 76% increase in prevalence among children 2–4 years old in the Texas Medicaid program between 1996 and 2000, and increases of over 100% in three of four Medicaid programs from 1996 to 2001 (Patel et al. 2006). Cooper and colleagues (2004) reported that in the Tennessee Medicaid program the 2–5-year-old group exhibited the greatest increase (61%) in new antipsychotic recipients. A similar increasing trend was observed among commercially insured children ages 2–5 years old. From 1999–2000 to 2007 antipsychotic prevalence increased from 0.78/1,000 children to 1.59/1,000 (Olfson et al. 2010).

Some data are available on the characteristics of antipsychotic recipients in this age group. For example, they tend to be male (Patel et al. 2002, 2005; Zito et al. 2007) and although the data on diagnoses are not consistent across studies, it appears that attention-deficit/hyperactivity disorder (ADHD), disruptive behavior disorders, pervasive developmental disorders, and bipolar disorder figure prominently among antipsychotic recipients (Cooper et al. 2006; Patel et al. 2006; Rani et al. 2008). We aimed to increase our knowledge about very young antipsychotic recipients by identifying a cohort of children who received antipsychotic treatment before their sixth birthday. We describe their diagnostic characteristics and medication experiences during the year before and the year after the start of treatment. This article represents the first results from a long-term longitudinal study of children who received antipsychotic treatment before their sixth birthday.

Methods

The study was reviewed and approved by the University of South Florida Institutional Review Board. Informed consent requirements were waived since the study utilized only administrative data. The study used Medicaid claims data (fee-for-service pharmacy, physician services, and institutional claims) and Medicaid identification numbers to identify a cohort of children under 6 years of age who were enrolled in the Florida Medicaid Program and who initiated an antipsychotic treatment episode at any time between 7/1/03 and 6/30/04. To determine if this cohort of antipsychotic recipients was different from the general Medicaid fee for service population, we compared their demographic and enrollment characteristics with those of all enrollees who were <6 years old on 1/1/2004 but did not receive antipsychotic treatment during the 365 days before or after that date. Approximately 50% of all Medicaid enrollees in this age group were in the fee for service program during the 7/1/03–6/30/04 period. The remaining children were in health maintenance organizations, and their pharmacy services were paid on a prospective, capitated basis. Pharmacy claims are not available on health maintenance organization (HMO) enrollees in Florida Medicaid.

National Drug Codes (National Drug Codes Directory 2008) were used to identify antipsychotic and other psychotherapeutic medications. A child was identified as initiating an antipsychotic treatment episode if he or she filled two or more consecutive prescriptions for an antipsychotic medication during the 7/1/03–6/30/04 period with a gap no greater than 15 days between the last day supplied from the earlier prescription to the re-fill date of the next prescription. To qualify as an index episode, the child could not have had an antipsychotic prescription that covered any of the 16 days immediately preceding the start of the index episode. A gap of 15 days was used because the vast majority of claims for antipsychotic medications in Florida Medicaid are for 30 days and the standard method of gap analysis uses one half of the days supplied as the cutoff (Sikka et al. 2005). The date of initiation of the first antipsychotic episode within the 7/1/2003–6/30/2004 period starts the beginning of the index antipsychotic treatment episode. The length of the index episode was the number of days from this start to the last day any antipsychotic medication was received within the episode. Gaps in therapy of 15 days or less were included in episode durations. The index antipsychotic episode was considered to be terminated when a gap in treatment exceeded 15 days.

To study the medication treatment experiences of the cohort, we looked back and forward 365 days from the start of each child's index antipsychotic treatment episode (preindex and index periods). In describing the psychotherapeutic medication usage of the cohort, children were classified as receiving “antipsychotic only” treatment during the index and preindex periods if their filled prescriptions covering the periods included only antipsychotic medications. These children were classified as “antipsychotic plus” if they had days that were covered by prescriptions for either stimulants, antidepressants, alpha-adrenergic agonists, and/or mood stabilizers in addition to antipsychotic medications during these periods regardless of whether or not the antipsychotic and nonantipsychotic medications were taken on the same days. Children were classified as “non-antipsychotic users” if they had days covered by prescriptions for stimulants, antidepressants, alpha-adrenergic agonists, or mood stabilizers during the preindex periods but no days covered by a prescription for an antipsychotic medication. They were classified as “non-users of psychotherapeutic medications” in the preindex periods if they had no days in the periods that were covered by a prescription for either antipsychotics, stimulants, antidepressants, alpha-adrenergic agonists, or mood stabilizers. There were not any nonusers in the index periods since all children in the cohort filled two or more antipsychotic prescriptions during these periods.

Since diagnoses of children receiving psychiatric care can vary over time, we assigned to each participant the diagnosis that appeared most frequently in their services claims data during their index and during their preindex periods. For children who had more than one diagnosis during these periods, the diagnosis that appeared most frequently in the service claims data was used. Schizophrenia, childhood schizophrenia, schizoaffective disorder, and other psychotic disorders were combined into a “psychotic disorders” category. Conduct disorder, oppositional defiant disorder, and other disruptive behavior disorders were combined into a category labeled “disruptive behavior disorders.” For each participant, the birth date was obtained from the Medicaid recipient information files. The participant's age was calculated as of the beginning of the index antipsychotic episode. Children were divided into two enrollment categories—Social Security Income (SSI) and all others including Temporary Assistance for Needy Families and Sixth Omnibus Reconciliation Act based on their enrollment status during their index periods. If they had an SSI enrollment status at any time during a period, they were placed in this enrollment category for that period. The ethnic/racial categories used (white, black, Hispanic, and other nonwhite) were those available in the Medicaid recipient information files. “Other non-white” includes American Indian and Asian and is also used for individuals who identify themselves as multiracial.

Analysis

The characteristics of antipsychotic users were compared with the characteristics of the nonantipsychotic recipient population of enrollees in Florida's fee for service program who aged under 6 years using separate logistic regression analyses, with two-tailed p-values <0.05 indicating statistical significance. Percentages were used to describe the use of each antipsychotic medication as well as the various combinations of antipsychotic and other classes of psychotherapeutic medications used during each period. Means and medians describe antipsychotic episode lengths and days of antipsychotic exposure.

Results

Treatment and comparison groups

We identified 528 children under 6 years of age who initiated an antipsychotic treatment episode between 7/1/03 and 6/30/04. The demographic and enrollment characteristics of these children are presented in Table 1 and compared to nonrecipients in the Medicaid fee for service population.

Table 1.

Demographic Characteristics of Antipsychotic Recipients Versus Nonantipsychotic Recipients <6 Years Old in the Florida Medicaid Fee for Service Program

	Antipsychotic recipients		Nonantipsychotic recipients
	n	%	n	%	OR	95% CI	p-Value
Gender
Female	141	26.7	55,619	48.1	Ref.	—	—
Male	387	73.3	59,931	51.9	2.6	2.1–3.1	<0.001
Total	528	100	115,550	100
Race/ethnicity
White	184	34.9	33,293	28.8	Ref.	—	—
Black	68	12.9	36,056	31.2	0.3	0.3–0.5	<0.001
Hispanic	48	9.1	32,461	28.1	0.3	0.2–0.4	<0.001
Other nonwhite	228	43.2	13,740	11.9	3.0	2.5–3.7	<0.001
Total	528	100	115,550	100
Age, \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland,xspace}\usepackage{amsmath,amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6} \begin{document}$$ \bar{\rm x}$$\end{document} = 4.3, median = 5
<4 years old	93	17.6	79,632	68.9	Ref.	—	—
4 years old	154	29.2	18,777	16.3	7.04	5.4–9.1	<0.001
5 years old	281	53.2	17,141	14.8	14.1	11.2–17.9	<0.001
Total	528	100	115,550	100
Enrollment status
TANF/SOBRA/other	264	50	106,462	92.1	Ref.	—	—
SSI	264	50	9,088	7.9	11.9	10.0–14.0	<0.001
Total	528	100	115,500	100

95% CI = 95% confidence interval; OR = odds ratio; Ref. = reference; SSI = Supplemental Security Income; TANF/SOBRA = Temporary Assistance for Needy Families/Sixth Omnibus Reconciliation Act; \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland,xspace}\usepackage{amsmath,amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6} \begin{document}$$ \bar{\rm x}$$\end{document} = mean.

Almost three quarters (73.3%) of our sample were male; 43.2% were other non-white, 34.9% were white, 12.9% black, and 9.1% Hispanic. The mean and median ages were 4.3 (±0.98) and 5 years. Fifty percent of the cohort had an SSI enrollment status. Children receiving antipsychotic medication were 2.6 times (p < 0.001) more likely than nonrecipients to be male and enrolled as SSI (odds ratio [OR] = 11.9, p < 0.001). They were less likely to be black or Hispanic compared with white (OR = 0.3, p < 0.001 and OR = 0.3, p < 0.001 for two groups, respectively) but more likely to be of other race/ethnicity compared with white (OR = 3.0, p < 0.001).

Preindex period diagnosis and treatment

The diagnostic classification and medication usage of the cohort during the preindex periods are presented in Table 2.

Table 2.

Diagnosis and Psychotherapeutic Medications Used in Preindex Periods

	n	%
Diagnosis during the preindex periods
No diagnosis	86	16.3
ADHD	242	45.8
Bipolar disorder	10	1.9
Pervasive developmental disorders	45	8.5
Psychotic disorders	11	2.1
Disruptive behavior disorders	97	18.4
Other adjustment disorders	31	5.9
Other	6	1.1
Total	528	100
Medications used during preindex periods
No psychotherapeutic medication	89	16.9
Any class of psychotherapeutic medication	439	83.1
Total	528	100
Only nonantipsychotic treatment stimulants/antidepressants/alpha-adrenergic agonists/mood stabilizers	136	31
Antipsychotic treatment alone or in combination with above classes	303	69
Total	439	100
Antipsychotic treatment only	71	23.4
Antipsychotic treatment in combination with above classes	232	76.6
Total	303	100
Antipsychotic treatment in preindex periods by age at index episode
<4 years old	40	13.2
4 years old	88	29.0
5 years old	175	57.8
Total	303	100

ADHD = attention-deficit/hyperactivity disorder.

Eighty-four percent of the cohort had a psychiatric diagnosis during their preindex periods. ADHD and disruptive behavior disorders occurred most frequently (45.8% and 18.4%, respectively). Eighty-three percent of the cohort had already been treated with some psychotherapeutic medication during the preindex periods. Among these children 31% (136/438) were treated exclusively with nonantipsychotic agents, whereas 69% (303/439) received some antipsychotic treatment. Among the latter group, 23.4% (71/303) received only antipsychotic treatment, whereas 76.6% (232/303) received both antipsychotics and one or more other classes of psychotherapeutic medications (antipsychotic plus group), including stimulants, antidepressants, alpha agonists, and/or mood stabilizers. Most (57.8%, 175/303) of the children who received antipsychotic treatment in their preindex periods were 5 years old at the start of their index episodes. However, 29% (88/303) were 4 years old and 13.2% (40/303) were <4 years old. Forty of the 93 children (from Table 1) who were <4 years old when they began their index antipsychotic treatment episode had been exposed to antipsychotic treatment during the preindex periods. The corresponding numbers for 4- and 5-year-olds were 57.1% (88/154) and 62.3% (175/281), respectively.

Index episode duration and antipsychotic medications dispensed

Table 3 describes the characteristics of the index antipsychotic episodes.

Table 3.

Characteristics of Index Antipsychotic Episodes

Episode lengths (Days) \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland,xspace}\usepackage{amsmath,amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6} \begin{document}$$ \bar{\rm x}$$\end{document} = 266.9 (±286.8); median = 173.5
Duration categories (days)	n	%
60–89	113	21.4
90–179	164	31.1
180–364	144	27.3
365+	107	20.3
Total	528	100
Antipsychotic agents used	n	%
Aripiprazole	28	5.3
Olanzapine	63	11.9
Quetiapine	59	11.2
Risperidone	367	69.5
Ziprasidone	9	1.7
First-generation antipsychotics	2	0.40
Total	528	100

Mean and median episode lengths were 266.9 (±286.8) and 173.5 days, respectively. Slightly more than a fifth of the cohort (21.4%) had episode lengths that were <90 days, and 20.2% had episode lengths that lasted a year or more. Risperidone was by far the most frequently used antipsychotic medication (69.5%), followed by olanzapine (11.9%) and quetiapine (11.2%). First-generation antipsychotic medications were used with only two children.

Diagnosis and treatment during the index periods

Table 4 describes the diagnoses and psychotherapeutic medications used by children during their index periods.

Table 4.

Diagnosis and Medication Usage During Index Periods

	n	%
Diagnosis during the index periods
No diagnosis	53	10.4
Attention-deficit hyperactivity disorder	264	50
Bipolar disorder	28	5.3
Pervasive developmental disorders	51	9.7
Psychotic disorders	16	2.8
Disruptive behavior disorders	76	14.4
Other adjustment disorders	25	4.7
Other	15	2.8
Total	528	100
Medications used during index periods
Antipsychotic used only	142	26.9
Antipsychotic plus	386	73.1
Total	528	100
(Days of antipsychotic exposure) \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland,xspace}\usepackage{amsmath,amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6} \begin{document}$$ \bar{\rm x}$$\end{document} = 263.3 (±84.8); median = 175
Antipsychotic + combinations
Antipsychotic + stimulants only	200	51.8
Antipsychotic + alpha-adrenergic agonists only	53	13.7
Antipsychotic + antidepressants only	17	4.4
Antipsychotic + mood stabilizers only	2	0.5
Antipsychotic + 2 or more of above	114	29.6
Total	386	100

ADHD, disruptive behavior disorders, and pervasive developmental disorders appeared most frequently accounting for 50%, 14.4%, and 9.7% of the children in the cohort, respectively. More than 1 in 10 children (n = 53) had no psychiatric diagnosis in their services claims during these periods.

During the index periods 26.9% (142/528) of children received only antipsychotic medications, whereas 73.1% (386/528) received antipsychotics plus one of the other classes of psychotherapeutic medications. In the “antipsychotic plus group” the combination of antipsychotics and stimulants accounted for 51.8% (200/386) of the children and antipsychotics and alpha-adrenergic agonists accounted for 13.7% (53/386). Almost 30% (114/386) of the children in the “antipsychotic plus group” received two or more classes of psychotherapeutic medications in addition to antipsychotic treatment during their index periods.

Discussion

We identified a cohort of children under 6 years old who initiated an antipsychotic treatment episode during the 7/1/03–6/30/04 period (index episodes) and described their psychiatric diagnoses and psychotherapeutic medication experiences during the 365 days before the start of these index episodes. We also described the durations and characteristics of the index episodes as well as the diagnoses and medication usage experienced by children in the cohort during the 365 days after the initiation of their index episodes. Our group of antipsychotic recipients appears to have been much more disabled than the nonantipsychotic recipients in the fee for service Medicaid program. Fully half of the cohort was disabled enough to achieve a social security disability status before their sixth birthday compared with 7.9% for the nonrecipient comparison group. Consistent with the findings of previous studies of pediatric antipsychotic recipients in older age groups, and also of recipients of other psychotherapeutic medications classes (Olfson et al. 2006), whites were overrepresented in the antipsychotic recipient group and blacks and Hispanics were underrepresented. Surprisingly the other non-white racial category, which included oriental, American Indian, and mixed racial groups, was significantly overrepresented in the recipient group compared with the nonrecipient group (42.2% vs. 11.9%).

Psychiatric disorders were diagnosed at a very early age for children in the cohort. Fully 83.7% of the recipient group under 6 years old had a psychiatric diagnosis during the 365 days preceding the index antipsychotic episode, indicating that emotional problems were present when almost half of the children were <5 years old. The response to these disorders most often involved the use of some psychotherapeutic agent. In all, 83.1% of the cohort had received some psychotherapeutic agent during their preindex periods and the use of antipsychotic medications was involved in the treatment of 69% of these children. Medication regimens for these children appeared to have been complex with 76.6% of children treated with antipsychotic medications during the preindex periods also treated with stimulants, antidepressants, alpha agonists, and/or mood stabilizers during the same 1-year periods. It is remarkable to observe that of the 93 children in the cohort who were <4 years old at the start of their index episode, 43% had already filled at least one prescription for antipsychotic medications during the previous year when they were 3 years old or younger.

Antipsychotic treatment during the index episodes primarily involved risperidone (69.5%). Since there were no antipsychotic formulary restrictions in the Medicaid fee for service program in Florida during the 7/03–6/04 period, the tendency to use risperidone was probably driven by the data published in the early 2000s, indicating that risperidone may be effective in the treatment of disruptive behavior disorder and of irritability and impulsivity of children with autism (McCracken et al. 2002; McClellan and Werry 2003).

The use of antipsychotic medications with children in the cohort was neither brief nor episodic. Index treatment episodes lasted an average of 266.9 days. Almost half of the episodes lasted 6 months or more, and more and a fifth lasted a year or more.

Treatment during the index periods included the use of other classes of psychotherapeutic medications in addition to antipsychotics for 73.1% of the children. The diagnoses that appeared most frequently among children during the index periods clearly did not support antipsychotic monotherapy or combinations of antipsychotic and nonantipsychotic medications, although severe irritability and behavior problems were probably present. The severity of the problems of these youth is supported by their use of Medicaid-funded mental health services. During their index periods, 94% (496/528) of the children in the cohort received mental health services in addition to medications. Eighty-one percent (428/528) used outpatient mental health services, 25% (132/528) used case management services, and 7.2% (38/528) received inpatient psychiatric care during their index periods. Mean and median days of outpatient services were 61 (±84.8) and 13.5 (Constantine 2010).

The use of antipsychotic medications with very young children presents a major dilemma. On the one hand, there are some data supporting their efficacy in treating severe behavior problems in youth (Jensen et al. 2007). In addition, discontinuation of antipsychotic regimens among some children with these problems appears to result in a recurrence of symptoms, suggesting that long-term and sustained use may be required (Reyes et al. 2006). On the other hand, antipsychotic use among very young children probably involves significant risk. Little is known about the effects of long-term use in pediatric populations. Concerns have been raised about the potential effects of these medications on cardiovascular and metabolic health and on the developing brain (Coyle 2000; Patel et al. 2005; Gleason et al. 2007; Olfson et al. 2010). Studies of the interaction between psychotropics and the developing brain in animals have reinforced these safety concerns (Vitiello 1998). Even exposure to antipsychotic medications for a single year was associated with significantly greater movement disorders and weight gain compared with children who were exposed for only 1 month (Laita et al. 2007). Although these findings are not specific to very young children, if children who are naïve to antipsychotic medications are the most sensitive to their side effects, as suggested by Correll et al. (2009), then we would expect very young children who start antipsychotic treatment to be particularly vulnerable. It was concern for this vulnerability that led the Florida Medicaid agency to require a review of the use of antipsychotics among very young children. Beginning in early 2008, all requests to use antipsychotic medications for children under 6 years old were subjected to review by consulting child psychiatrists. The review included diagnostic and target symptom criteria as well as requirements for monitoring plans (flmedicaidbh.fmhi.usf.edu). The impact of this program is currently being evaluated.

Limitations

The findings presented here should be interpreted with caution for several reasons. First, we used exclusively administrative data that were available only for children in the fee for service program. Second, a diagnosis could be established for a child only if the child saw a physician and the physician recognized a disorder and submitted a claim for payment. Therefore, the prevalence of various disorders presented here is likely an underestimate of the true diagnostic pictures of these children. Third, the diagnoses used were those that appeared in the claims. They were not validated by reliable diagnostic tools. Fourth, we have no data on the target symptoms of antipsychotic or other psychotherapeutic medication treatment. This information may be more informative regarding the purpose and rationales for antipsychotic treatment than the diagnosis information we report. Finally, medications could have been secured from other sources, for example, samples. Consequently, we may have underestimated medication use.

Conclusions

We found 528 very young children who initiated antipsychotic treatment episodes during the 7/03–6/04 period. The diagnostic and medication histories of these children suggest that they had developed significant emotional disturbances well before their sixth birthday. Most of these children were exposed extensively to antipsychotics as well as to a variety of other classes of psychotherapeutic medications at very early ages. It may be that severe impulsivity and aggression are target symptoms, but this cannot be established with the claims data. While early identification of emotional problems may be beneficial, it appears to result in very early exposure to antipsychotic and other psychotherapeutic medications. The accumulating data on the sensitivity of young children to the side effects of these medications suggest that this early and extensive exposure is a cause for concern.

Disclosures

Robert J. Constantine is currently and has for the last 4 years been supported in part by a contract with the Florida Agency for Health Care Administration, the State Medicaid authority. In the past 4 years Dr. Constantine has also been funded in part by research contracts with Bristol Myers Squibb and Ortho McNeil Janssen. Rajiv Tandon has no disclosures to make. Marie McPherson is currently supported by a contract with the Florida Agency for Health Care Administration, the State Medicaid authority. Similar contracts have provided support for the last 4 years. Ross Andel has no disclosures to make.

Footnotes

This research was funded by the Florida Agency for Health Care Administration, the Single State Medicaid Authority.

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