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Original Article |

National Trends in the Office-Based Treatment of Children, Adolescents, and Adults With Antipsychotics FREE

Mark Olfson, MD, MPH; Carlos Blanco, MD, PhD; Shang-Min Liu, MS; Shuai Wang, PhD; Christoph U. Correll, MD
[+] Author Affiliations

Author Affiliations: New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University (Drs Olfson, Blanco, and Wang and Ms Liu), Albert Einstein College of Medicine, Bronx, and Zucker Hillside Hospital, North Shore–Long Island Jewish Health System, Glen Oaks (Dr Correll), New York.


Arch Gen Psychiatry. 2012;69(12):1247-1256. doi:10.1001/archgenpsychiatry.2012.647.
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Published online

Context Although antipsychotic treatment has recently increased, little is known about how this development has differentially affected the office-based care of adults and young people in the United States.

Objective To compare national trends and patterns in antipsychotic treatment of adults and youths in office-based medical practice.

Design Trends between 1993 and 2009 in visits with antipsychotics for children (0-13 years), adolescents (14-20 years), and adults (≥21 years) are described on a per population basis and as a proportion of total medical office visits. Background and clinical characteristics of recent (2005-2009) antipsychotic visits are also compared by patient age.

Setting Outpatient visits to physicians in office-based practice.

Participants Visits from the 1993-2009 National Ambulatory Medical Care Surveys (N = 484 889).

Main Outcome Measures Visits with a prescription of antipsychotic medications.

Results Between 1993-1998 and 2005-2009, visits with a prescription of antipsychotic medications per 100 persons increased from 0.24 to 1.83 for children, 0.78 to 3.76 for adolescents, and 3.25 to 6.18 for adults. The proportion of total visits that included a prescription of antipsychotics increased during this period from 0.16% to 1.07% for youths and from 0.88% to 1.73% for adults. From 2005 to 2009, disruptive behavior disorders were the most common diagnoses in child and adolescent antipsychotic visits, accounting for 63.0% and 33.7%, respectively, while depression (21.2%) and bipolar disorder (20.2%) were the 2 most common diagnoses in adult antipsychotic visits. Psychiatrists provided a larger proportion of the antipsychotic visits for children (67.7%) and adolescents (71.6%) than to adults (50.3%) (P < .001). From 2005 to 2009, antipsychotics were included in 28.8% of adult visits and 31.1% of youth visits to psychiatrists.

Conclusions On a population basis, adults make considerably more medical visits with a prescription of antipsychotics than do adolescents or children. Yet antipsychotic treatment has increased especially rapidly among young people, and recently antipsychotics have been prescribed in approximately the same proportion of youth and adult visits to psychiatrists.

Over the past several years, an increasing number of adults and children in the United States have been treated with antipsychotic medications.1,2 Antipsychotics are now among the most commonly prescribed and costly classes of medications.3 In adults, antipsychotic medications have demonstrated efficacy and have been approved by the Food and Drug Administration (FDA) as a primary treatment for schizophrenia4,5 and bipolar disorder6,7 and as an adjunctive treatment for major depressive disorder.8 In children and adolescents, antipsychotics are indicated for irritability associated with autistic disorder (5-16 years), tics and vocal utterances of Tourette syndrome and bipolar mania (10-17 years), and schizophrenia (13-17 years).9

With increasing use of antipsychotic drugs, the range of mental disorders treated with these medications in practice has broadened.1015 As a result, the proportion of second-generation antipsychotic medications prescribed to treat schizophrenia has decreased from 51% (1995-1996) to 24% (2007-2008),2 while antipsychotic treatment of anxiety disorders in adults and youths has roughly doubled.12 In young people, attention-deficit/hyperactivity disorder and other disruptive disorders account for a substantial proportion (37.8%) of antipsychotic use.11

The metabolic safety concerns of antipsychotic medications16,17 focus our attention on antipsychotic prescribing practices in the community, especially on the extent to which antipsychotics are used to treat disorders for which there is limited empirical evidence of efficacy.15,18 Young people may be especially sensitive to the adverse metabolic effects of second-generation antipsychotics. As compared with adults, children may be more vulnerable to antipsychotic-induced weight gain19 and perhaps even to antipsychotic-associated diabetes.20,21

Young people and adults vary in several important clinical respects22 that might influence trends in antipsychotic use. Disruptive behavioral disorders, which are more commonly diagnosed in boys than in girls23 and in nonwhite youths than in white youths,24,25 occur in a substantial proportion of young people receiving outpatient mental health care.26 Increasing clinical acceptance of antipsychotics for problematic aggression in disruptive behavior disorders27 may have increased the number of children and adolescents (especially male youths and ethnic/racial minorities) being prescribed antipsychotics. The increase in the number of clinical diagnoses of bipolar disorder28 and autistic spectrum disorders29 among children and adolescents may have further increased antipsychotic use by youths, particularly by boys. With respect to adults, acceptance of antipsychotics as adjuvant treatment of major depressive disorder, even in the absence of psychotic features,30 might have increased antipsychotic use. Because depressive disorders are significantly more common in women than in men,31 such a trend might preferentially increase antipsychotic use among adult women. Increasing use of antipsychotics in adult anxiety disorders may have a similar effect.12

A comparison is presented of nationally representative survey data from adult and youth visits to office-based physicians. The analyses focus on trends and patterns of antipsychotic treatment. Prior to conducting these analyses, we predicted that the increase in the proportion of physician visits with a prescription of antipsychotic medications would be more pronounced for youths than for adults.

Data were obtained from the National Ambulatory Medical Care Survey (NAMCS).32 The NAMCS, which is conducted annually by the National Center for Health Statistics, samples a nationally representative group of visits to physicians in office-based practice. Following National Center for Health Statistics recommendations, data from contiguous survey years were combined to derive more stable estimates (1993-1998, 1999-2004, and 2005-2009). Across the 17 survey years, response rates varied between 58.9% (2006) and 73.1% (1993), with a mean of 66.1%.33 For each visit, the treating physician or member of the physician's staff provided information about patient sociodemographic and clinical characteristics, as well as the medications prescribed or supplied to the patient.

DIAGNOSIS

Diagnoses were made according to the International Classification of Diseases, Ninth Revision, Clinical Modification. For the analysis of trends in antipsychotic use stratified by age groups, visits were grouped by occurrence of mood, anxiety, and psychotic disorders. In the analysis that compares the characteristics of antipsychotic visits across age groups (2005-2009), visits were classified by diagnoses of schizophrenia and related psychotic disorders, bipolar disorder, depression, anxiety, developmental disorders or mental retardation, disruptive behavior disorders, and other mental disorders (eTable).

PSYCHOTROPIC MEDICATIONS

Visits in which psychotropic medications were either supplied or prescribed were classified into 5 medication groups: antipsychotic medications, which are the primary focus of the analyses; stimulants and other attention-deficit/hyperactivity disorder medications; antidepressants; anxiolytics/hypnotics; and mood stabilizers. The antipsychotic medication group excluded prochlorperazine edisylate and promethazine hydrochloride because they are commonly used for nonpsychiatric indications. Anxiolytics/hypnotics included benzodiazepines and nonbenzodiazepine sedatives and anxiolytics. Mood stabilizers included lithium carbonate or lithium citrate, carbamazepine, divalproex sodium/valproate sodium/valproic acid, and lamotrigine. All antidepressants including those such as bupropion hydrochloride, duloxetine hydrochloride, and trazodone hydrochloride, which are also used for non–mental health indications, were included.

SOURCE OF PAYMENT

Data were collapsed into 3 nonmutually exclusive categories: (1) private insurance such as Blue Cross/Blue Shield and other commercial insurance; (2) public insurance, including Medicare, Medicaid, and other government insurance; and (3) a residual category (“self-pay/other”) that combined patients with self-payment, no charge, workers compensation, those whose source of insurance was unknown, and those who received uncompensated care. In visits with more than 1 source of payment, assignment was hierarchical, with visits assigned to private, public, and self-pay/other insurance groups in descending order.

FDA-APPROVED INDICATION

One or more antipsychotics have been approved for schizophrenia or schizoaffective disorder, bipolar disorder, autistic disorder, Tourette syndrome, and major depressive disorder when coprescribed with an antidepressant. In the following analysis, FDA-approved visits include only those visits with a diagnosis for which the specific prescribed antipsychotic had been approved by the visit year for the age of the patient. This definition recognizes the substantial within-class heterogeneity in safety34 and efficacy35 that exists among antipsychotic medications and is consistent with the FDA's approach of drug indication approval at the level of individual drugs.

OTHER CHARACTERISTICS

Visits were also classified by patient sex, patient race/ethnicity (white, non-Hispanic, or other), specialty of the treating physician (psychiatrist or nonpsychiatrist), and whether psychotherapy was provided by the physician at the visit.

ANALYTIC STRATEGY

Population-based proportions and associated 95% CIs of office-based adult (≥21 years), adolescent (14-20 years), and child (0-13 years) visits with antipsychotic treatment (hereafter referred to as antipsychotic visits) were determined for the time periods of 1993-1998, 1999-2004, and 2005-2009. Denominators were derived from intercensal estimates from the US Bureau of the Census36 of the corresponding demographic groups (Table 1). For years 2005-2009, population-based proportions of office-based antipsychotic visits with surrounding 95% CIs were determined for the 3 age groups (0-13, 14-20, and ≥21 years), sex, and broad race/ethnicity group (Table 2).

Table Graphic Jump LocationTable 1. Trends in National Annualized Population Estimates of Office-Based Physician Visits for Children, Adolescents, and Adults That Included Antipsychotic Treatmenta
Table Graphic Jump LocationTable 2. National Estimated Number of Office-Based Medical Visits by Children, Adolescents, and Adults That Included Antipsychotic Treatment (2005-2009)a

The proportions of youth (0-20 years) and adult (≥21 years) office-based antipsychotic visits were determined overall and stratified by patient sex, patient race/ethnicity, payment source, physician specialty, psychotherapy, broad mental disorder group, and FDA-approved indication for each time period (1993-1998, 1999-2004, and 2005-2009). Logistic regression models were used to assess time trends in the probability of antipsychotic visits. A study period variable was defined for each survey year running from 0 for 1993 to 1 for 2009. The outcome of interest is the odds of an antipsychotic across the entire period (1993-2009). For example, an odds ratio of 2.0 denotes twice the odds that a visit included an antipsychotic at the end (2009) as compared with the start (1993) of the study period. Separate regressions were constructed for each level of visit characteristics of interest. For example, one regression assessed the odds of antipsychotic visits over the study period for male visits and a separate regression for female visits. An interaction term was added to each regression to assess whether trends in antipsychotic use significantly differed across these groups. The P values associated with these interaction terms are presented in Tables 3 and 4.

Table Graphic Jump LocationTable 3. Trends in Antipsychotic Prescribing Patterns in Youth and Adult Office-Based Visits, Stratified by Background Characteristics
Table Graphic Jump LocationTable 4. Trends in Antipsychotic Prescribing Patterns in Youth and Adult Office-Based Visits, Stratified by Clinical Characteristics

For years 2005-2009, the difference in proportion test was used to compare the background and clinical characteristics of antipsychotic visits for children, adolescents, and adults during the period from 2005 to 2009. A separate analysis compared the clinical characteristics of youth and adult antipsychotic visits by specialty of the treating physician (psychiatrist vs nonpsychiatrist). The frequency distribution in the time period of 2005-2009 of the 4 most commonly prescribed antipsychotics in each age group was also determined.

Analyses were adjusted for visit weights, clustering, and stratification of data using design elements provided by the National Center for Health Statistics. When adjusted for these elements, survey data represent annual visits to US office-based physicians.37 Analyses were conducted using SUDAAN software (Research Triangle Institute), all analyses were 2 sided, and α was set at .05.

TRENDS IN ANTIPSYCHOTIC VISITS ON A POPULATION BASIS

On a per capita basis, office-based antipsychotic visits increased among all 3 age groups but were consistently more prevalent for adults than for adolescents and were least prevalent for children (Table 1). During the 2005-2009 time period, the estimated number of antipsychotic visits per 100 adults was significantly greater for female than male patients, while the reverse was true for children (Table 2). For adolescents and adults, but not children, the corresponding proportion of antipsychotic visits was significantly greater on a per population basis for white non-Hispanics than for the other racial/ethnic group.

TRENDS IN ANTIPSYCHOTIC USE AMONG ADULT AND YOUTH VISITS

During the study period, antipsychotic use increased among adult and youth visits, with a significantly greater increase by youths. Antipsychotic use increased especially rapidly among visits by young people who were male, non-Hispanic white in race/ethnicity, and who paid for their care with private insurance or other nonpublic sources. Antipsychotic use also significantly increased among visits by youths who were Hispanic or nonwhite. A corresponding increase did not, however, occur among adults who were Hispanic or nonwhite (Table 3).

Antipsychotic use was substantially more common in visits to psychiatrists than nonpsychiatrists (Table 4). Among visits to psychiatrists, antipsychotic use increased significantly more rapidly in visits by youths than adults. By 2005-2009, a similar proportion of youth and adult visits to psychiatrists included an antipsychotic medication. A marked increase also occurred in antipsychotic use among visits by youths to nonpsychiatrist physicians.

Throughout the study period, antipsychotic use was prevalent in visits by youths and adults with psychotic disorder diagnoses. There was a particularly marked increase in antipsychotics in visits by youths with mood disorder diagnoses. By 2005-2009, almost one-third of youth visits with a mood disorder diagnosis (31.3%) included an antipsychotic medication. A smaller, though nevertheless significant, increase also occurred in antipsychotic use by adult visits with mood disorder diagnoses. By contrast, antipsychotic use visits with anxiety disorder diagnoses increased in a roughly parallel manner among youth and adult visits (interaction P = .66) (Table 4).

CHARACTERISTICS OF CHILD, ADOLESCENT, AND ADULT ANTIPSYCHOTIC VISITS

In 2005-2009, several differences were evident in the demographic and clinical characteristics of antipsychotic visits by children, adolescents, and adults (Table 5). Male patients predominated among child and adolescent antipsychotic visits, while female patients predominated among adult antipsychotic visits. This was partially explained by a predominance of male patients (80.3% [95% CI, 73.8-85.4]) among child and adolescent antipsychotic visits with disruptive behavior disorders and a predominance of female patients (67.9% [95% CI, 63.6-71.6]) among adult antipsychotic visits with mood disorders (data not shown). Not surprisingly, schizophrenia, bipolar disorder, and depression accounted for a considerably larger percentage of adult than child antipsychotic visits, while disruptive behavior and developmental disorders accounted for a greater proportion of child than adult antipsychotic visits. Visits without a mental disorder diagnoses accounted for roughly one-third of adult antipsychotic visits. In a post hoc analysis, 96.5% of the adult antipsychotic visits without mental disorders were to nonpsychiatrist physicians, and 33.7% included a quetiapine fumarate prescription (data not shown).

Table Graphic Jump LocationTable 5. Demographic and Clinical Characteristics of Office-Based Physician Visits With Antipsychotic Treatment by Child, Adolescent, and Adult, 2005-2009a

During 2005-2009, antidepressants and anxiolytics were more often prescribed in adult antipsychotic visits than in child and adolescent antipsychotic visits, while the reverse was true of stimulants. Mood stabilizers were prescribed in roughly one-quarter of adolescent and adult antipsychotic visits, but only about 1 in 10 child antipsychotic visits (Table 5).

Only a small proportion of child and adolescent antipsychotic visits included an FDA clinical indication (Table 5). For child antipsychotic visits without an FDA indication, the 3 most common specific mental disorder diagnoses were attention-deficit/hyperactivity disorder (17.0%), oppositional defiant disorder (11.3%), and disruptive behavior disorder not otherwise specified (10.5%). The corresponding diagnoses for adolescent antipsychotic visits were bipolar disorder not otherwise specified (14.9%), anxiety disorder not otherwise specified (12.6%), and attention-deficit/hyperactivity disorder (11.4%), and, for adults, the 3 most common diagnoses in antipsychotic visits without an FDA indication were anxiety disorder not otherwise specified (17.7%), depression not otherwise specified (10.9%), and bipolar disorder not otherwise specified (10.3%) (data not shown).

An evaluation by physician specialty revealed that, compared with visits to psychiatrists, visits to nonpsychiatrist physicians by youths and adults that included antipsychotic medications were more likely not to include a mental disorder diagnosis. As a result, antipsychotic visits to psychiatrists were far more likely than those to nonpsychiatrists to include several specific mental disorder diagnoses. For example, a significantly larger percentage of youth and adult visits to psychiatrists than nonpsychiatrists included a bipolar diagnosis. As compared with antipsychotic visits to psychiatrists, antipsychotic visits to nonpsychiatrists were also significantly less likely to be for an FDA-approved indication. Only a small minority of youth and adult antipsychotic visits to nonpsychiatrists included an FDA-approved indicated diagnosis (Table 6).

Table Graphic Jump LocationTable 6. Clinical Characteristics of Office-Based Physician Visits With Antipsychotic Treatment of Youths and Adults by Physician Specialty, 2005-2009a
INDIVIDUAL ANTIPSYCHOTIC MEDICATIONS

The frequency distribution of antipsychotic medications varied across the 3 age groups (2005-2009). Among adult antipsychotic visits, the most commonly prescribed drugs were quetiapine (32.6%) followed by risperidone (16.9%), olanzapine (15.2%), and aripiprazole (13.8%). For adolescent visits, aripiprazole (29.0%), quetiapine (26.8%), risperidone (23.0%), and olanzapine (9.3%) were the 4 most common medications. Among child antipsychotic visits, the most commonly prescribed drugs were risperidone (42.1%), aripiprazole (28.0%), quetiapine (19.2%), and olanzapine (4.4%). First-generation antipsychotics represented a greater proportion of adult (11.9%) than child (1.3%) or adolescent (1.8%) antipsychotic medications (data not shown).

Antipsychotic treatment in office-based practice has increased for children, adolescents, and adults. Compared with children and adolescents, adults make a substantially larger number of per capita office-based visits that include antipsychotic prescriptions. Increasing antipsychotic use by adults has also been reported from several other industrialized countries, although trends among youths have not been studied outside the United States.38 When considered in the narrower context of US office-based care, antipsychotic treatment has increased more rapidly among youths than adults. By 2005-2009, antipsychotics were prescribed in roughly equal proportions of youth and adult visits to psychiatrists. Yet important differences exist in antipsychotic use across age groups. Although antipsychotic treatment of adults is concentrated among female patients and patients diagnosed with bipolar disorder, depression, or schizophrenia, antipsychotic treatment of children and adolescents predominantly involves male patients and is common among patients with disruptive behavior disorders.

Most of the youth and adult antipsychotic visits did not include a diagnosis for which the antipsychotic had FDA approval for the patient age group. The strength of evidence supporting efficacy for these “off-label” conditions varies considerably across psychiatric disorders and individual antipsychotics.18 Almost two-thirds of child antipsychotic visits in 2005-2009 included a disruptive behavior disorder diagnosis, and there are currently no FDA-approved medications for the treatment of disruptive disorders. Across all child visits during this period, risperidone was by far the most commonly prescribed antipsychotic. Uncertainty surrounds the appropriate role of risperidone and other antipsychotic medications in the management of disruptive behavior disorders. Although some have urged greater caution in the treatment of disruptive behavior disorders with antipsychotic medications given their uncertain effects on cognitive, social, and physical development,39 others note that risperidone tends to be well tolerated and beneficial for conduct disorder and other disruptive behavior disorders, particularly when there are problematic aggressive behaviors.40,41 Randomized clinical trials provide evidence of efficacy in the treatment of aggressive youths with subaverage intelligence,4143 although discontinuation related to lack of continued efficacy may be considerable over the longer term.43

Antipsychotic treatment in youth mood disorder visits increased especially rapidly during the study period. By 2005-2009, youth mood disorders visits, which were mostly for bipolar disorder, were more likely than their adult counterparts to include an antipsychotic medication. This pattern is consistent with pooled analyses indicating that the effect size of antipsychotics for bipolar mania, especially compared with mood stabilizers, is larger for youths than adults.44 The trend in the prescribing of antipsychotics to youths occurred within the context of a dramatic increase in the clinical diagnoses of bipolar disorder among young people.11,45 Concern exists, however, over the accuracy of community diagnoses of bipolar disorder in children and adolescents.46,47

A greater proportion of adult antipsychotic visits than child or adolescent antipsychotic visits do not include a diagnosed mental disorder. This is largely attributable to the proportionately greater role of nonpsychiatrist physicians in the treatment of adults with antipsychotics than in the treatment of young people. Nearly all of the adult antipsychotic visits without mental disorder diagnoses were provided by nonpsychiatrist physicians. Primary care physicians and other nonpsychiatrists sometimes deliberately mask their patients' mental health problems to minimize stigma, to prevent adverse legal or occupational consequences associated with seeking mental health treatment,48 or to capture more health plan benefits than would be available by providing mental health treatment.49 Because patient and physician identities are protected in the NAMCS, however, deliberately withholding mental disorder diagnoses from the survey data is unlikely to be widespread. The considerable degree to which antipsychotics are prescribed to adults and, to a lesser extent, young people without concomitant psychiatric diagnoses calls for further examination. It is possible that some of these patients have been treated with antipsychotic medications for an extended period of time and that, at the time of the survey visit, they were experiencing few psychiatric symptoms. Because the survey form captures only up to 3 diagnoses per visit, it may also not enumerate all mental disorder diagnoses. Alternatively, some physicians may prescribe quetiapine or other antipsychotics for insomnia,50 agitation,51 or other symptoms that do not rise to the threshold of a mental disorder.

Research on racial/ethnic variation in antipsychotic treatment has largely, but not exclusively,52 focused on patients with schizophrenia5356 or bipolar disorder.57,58 The present findings offer a somewhat broader perspective on trends in antipsychotic use by white and nonwhite patients. Nonwhite adults stand out from the other age-racial/ethnic groups as not experiencing a significant increase in antipsychotic treatment during the study period. This pattern is consistent with evidence that adult African Americans and Hispanics are less likely than white adults to find psychotropic medications acceptable.59,60 The roughly parallel increase in antipsychotic use among nonwhite youths and white youths during the study period is broadly consistent with research indicating that the race/ethnicity of adults is not strongly related to their willingness to give psychiatric medications to their children.61,62

Several factors may account for the increase in antipsychotic treatment within office-based practice. One factor may be the availability of new antipsychotics, including olanzapine (1997), quetiapine (1997), ziprasidone hydrochloride (2001), aripiprazole (2002), and paliperidone (2006), during the study period. Food and Drug Administration approval of antipsychotics to treat bipolar disorder, schizophrenia, and irritability associated with autistic disorder in youths, as well as various FDA approvals of adult indications, may also contribute to the increase in antipsychotic treatment. Clinical trials40 and clinical practice guidelines63 supporting antipsychotic use for youths outside of FDA-approved indications may have encouraged antipsychotic treatment of young people. The previously mentioned increase in the community diagnosis of bipolar disorder in young people, as well as increasing diagnosis of autism spectrum disorders,64,65 may have also played a role. Furthermore, lower rates of acute and chronic extrapyramidal adverse effects with second-generation antipsychotics compared with first-generation antipsychotics66 may also have increased the general ease of prescribing antipsychotics to vulnerable pediatric patients, even despite generally greater weight gain and metabolic risk with the newer agents.9,17 The proliferation of behavioral managed care67 and the attendant limitations on psychotherapy reimbursement68 may further shift practice toward psychopharmacological management.69 Cultural factors may also be at work, including a lessening of the stigma associated with mental health care, which is especially pronounced among young adults,70 and greater public acceptance of psychotropic medications.60 Pharmaceutical marketing,71 including the promotion of off-label use,72 likely also contributes to community antipsychotic prescribing practices. Finally, some patients may respond but not remit to evidence-based treatments, and, as a result, physicians endeavor to achieve remission by using antipsychotics as an adjunctive treatment.73,74

These analyses have several important limitations. First, the NAMCS samples visits rather than patients. Because an unknown quantity of patient duplication occurs and because patients may make several visits to several physicians each year, it is not possible to derive from the survey data an estimate of the number of unique people who are treated in office-based practice with antipsychotic medications each year. However, because each physician is randomly assigned to 1 of 52 weeks in the survey year, this duplication is likely to have only a limited effect on national estimates of unduplicated visits. Second, diagnoses in the NAMCS are based on the independent judgment of the treating physician, rather than research diagnostic interviews. Some primary care physicians may rely on diagnoses made by psychiatrists or other mental health specialists. Third, information is not available concerning dosages and duration of the antipsychotic medications. Dosages of antipsychotics for youths with disruptive behavioral disorders are likely to be considerably lower than that for youths with schizophrenia and other psychotic disorders.75 In addition, some patients with FDA-indicated disorders may receive subtherapeutic antipsychotic doses.76 Fourth, physician nonresponse may have biased the observed pattern of antipsychotic prescribing. Fifth, sample size limitations constrain efforts to evaluate the independence of associations between patient characteristics and provision of antipsychotic treatment. Sixth, since 2009, several developments, such as the approval of new antipsychotics (including asenapine [2009], lurasidone [2010], and iloperidone [2010]), labeling revisions strengthening the metabolic risk section regarding hyperglycemia and diabetes, dyslipidemia, and weight gain, and new practice guidelines,77 may have influenced antipsychotic prescribing patterns. Finally, the sample is restricted to office-based visits and therefore does not capture visits to community mental health centers, hospital outpatient clinics, or various other outpatient settings, nor does it capture visits to inpatient settings where mental health care is provided. In 2009, for example, there were approximately 54.8 million total antipsychotic prescriptions in the United States,78 of which approximately 18.9 million (34.5%) were from office-based settings included in the NAMCS scope. For these reasons, the population-based results should not be interpreted as representing population-wide antipsychotic use.

In summary, over a 17-year period, antipsychotic medications became more commonly used in office-based practice. The increase, which has been broad-based, has been especially concentrated among children and adolescents, particularly among youths diagnosed with mood disorders and those treated by nonpsychiatrist physicians. A substantial majority of child antipsychotic visits are for young people diagnosed with disruptive behavior disorders. In light of known safety concerns and uncertainty over long-term risks and benefits, these trends may signal a need to reevaluate clinical practice patterns and strengthen efforts to educate physicians, especially primary care physicians, concerning the known safety and efficacy of antipsychotic medications. At the same time, a new generation of clinical trials is needed to evaluate the safety and efficacy of antipsychotic medications in conditions for which they are commonly prescribed but for which the evidence base remains underdeveloped.

Correspondence: Mark Olfson, MD, MPH, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 1051 Riverside Dr, New York, NY (mo49@columbia.edu).

Submitted for Publication: November 17, 2011; final revision received March 12, 2012; accepted April 25, 2012.

Published Online: August 6, 2012. doi:10.1001 /archgenpsychiatry.2012.647

Author Contributions: Dr Wang had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: Dr Olfson reports that he has worked on grants to Columbia University from Eli Lilly and Bristol-Myers Squibb. Dr Correll reports that he has been a consultant and/or advisor to or has received honoraria from Actelion, Alexza, AstraZeneca, Biotis, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, Desitin, Eli Lilly, GlaxoSmithKline, IntraCellular Therapies, Lundbeck, Medavante, Medicure, Medscape, Merck, Novartis, Ortho-McNeill/Janssen/Johnson & Johnson, Otsuka, Pfizer, ProPhase, Schering-Plough, Sepracor/Sunovion, Supernus, Takeda, Teva, and Vanda. He has received grant support from Bristol-Myers Squibb, the Feinstein Institute for Medical Research, Janssen/Johnson & Johnson, the National Institute of Mental Health, the National Alliance for Research in Schizophrenia and Depression, and Otsuka.

Funding/Support: This research was funded by Agency for Healthcare Research and Quality grant U18 HS021112 (Dr Olfson), National Institute on Drug Abuse grant DA023200 (Dr Blanco), and National Institute of Mental Health grant MH076051 (Dr Blanco). Drs Olfson and Blanco are also supported by the New York State Psychiatric Institute.

Role of the Sponsors: The sponsors did not participate in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation or approval of the manuscript.

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PubMed   |  Link to Article
Maher AR, Maglione M, Bagley S, Suttorp M, Hu JH, Ewing B, Wang Z, Timmer M, Sultzer D, Shekelle PG. Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: a systematic review and meta-analysis.  JAMA. 2011;306(12):1359-1369
PubMed   |  Link to Article
Correll CU, Lencz T, Malhotra AK. Antipsychotic drugs and obesity.  Trends Mol Med. 2011;17(2):97-107
PubMed   |  Link to Article
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PubMed   |  Link to Article
Andrade SE, Lo JC, Roblin D, Fouayzi H, Connor DF, Penfold RB, Chandra M, Reed G, Gurwitz JH. Antipsychotic medication use among children and risk of diabetes mellitus.  Pediatrics. 2011;128(6):1135-1141
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Paus T, Keshavan M, Giedd JN. Why do many psychiatric disorders emerge during adolescence?  Nat Rev Neurosci. 2008;9(12):947-957
PubMed
Frick PJ, Lahey BB, Applegate B, Kerdyck L, Ollendick T, Hynd GW, Garfinkel B, Greenhill L, Biederman J, Barkley RA, McBurnett K, Newcorn J, Waldman I. DSM-IV field trials for the disruptive behavior disorders: symptom utility estimates.  J Am Acad Child Adolesc Psychiatry. 1994;33(4):529-539
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Nguyen L, Huang LN, Arganza GF, Liao Q. The influence of race and ethnicity on psychiatric diagnoses and clinical characteristics of children and adolescents in children's services.  Cultur Divers Ethnic Minor Psychol. 2007;13(1):18-25
PubMed   |  Link to Article
Yeh M, McCabe K, Hurlburt M, Hough R, Hazen A, Culver S, Garland A, Landsverk J. Referral sources, diagnoses, and service types of youth in public outpatient mental health care: a focus on ethnic minorities.  J Behav Health Serv Res. 2002;29(1):45-60
PubMed   |  Link to Article
Garland AF, Hough RL, McCabe KM, Yeh M, Wood PA, Aarons GA. Prevalence of psychiatric disorders in youths across five sectors of care.  J Am Acad Child Adolesc Psychiatry. 2001;40(4):409-418
PubMed   |  Link to Article
Findling RL. Atypical antipsychotic treatment of disruptive behavior disorders in children and adolescents.  J Clin Psychiatry. 2008;69:(suppl 4)  9-14
PubMed   |  Link to Article
Moreno C, Laje G, Blanco C, Jiang H, Schmidt AB, Olfson M. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth.  Arch Gen Psychiatry. 2007;64(9):1032-1039
PubMed   |  Link to Article
Kogan MD, Blumberg SJ, Schieve LA, Boyle CA, Perrin JM, Ghandour RM, Singh GK, Strickland BB, Trevathan E, van Dyck PC. Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007.  Pediatrics. 2009;124(5):1395-1403
PubMed   |  Link to Article
Mohamed S, Leslie DL, Rosenheck RA. Use of antipsychotics in the treatment of major depressive disorder in the U.S. Department of Veterans Affairs.  J Clin Psychiatry. 2009;70(6):906-912
PubMed   |  Link to Article
Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS.National Comorbidity Survey Replication.  The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).  JAMA. 2003;289(23):3095-3105
PubMed   |  Link to Article
Sham PC, MacLean CJ, Kendler KS. A typological model of schizophrenia based on age at onset, sex and familial morbidity.  Acta Psychiatr Scand. 1994;89(2):135-141
PubMed   |  Link to Article
 2009 NAMCS micro-data file documentation. National Center for Health Statistics/Centers for Disease Control and Prevention website. ftp://ftp.cdc.gov/pub/Health_Statistics/NCHS/Dataset_Documentation/NAMCS/doc09.pdf. Accessed February 12, 2012
Glick ID, Correll CU, Altamura AC, Marder SR, Csernansky JG, Weiden PJ, Leucht S, Davis JM. Mid-term and long-term efficacy and effectiveness of antipsychotic medications for schizophrenia: a data-driven, personalized clinical approach.  J Clin Psychiatry. 2011;72(12):1616-1627
PubMed   |  Link to Article
Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis.  Lancet. 2009;373(9657):31-41
PubMed   |  Link to Article
 Population estimates. United States Bureau of the Census website. http://www.census.gov/popest/. Accessed November 1, 2011
Cherry DK, Hing E, Woodwell DA, Rechtsteiner EA. National Ambulatory Medical Care Survey: 2006 summary.  Natl Health Stat Report. 2008;(3):1-39
PubMed
Verdoux H, Tournier M, Bégaud B. Antipsychotic prescribing trends: a review of pharmaco-epidemiological studies.  Acta Psychiatr Scand. 2010;121(1):4-10
PubMed   |  Link to Article
McKinney C, Renk K. Atypical antipsychotic medications in the management of disruptive behaviors in children: safety guidelines and recommendations.  Clin Psychol Rev. 2011;31(3):465-471
PubMed   |  Link to Article
Findling RL. Atypical antipsychotic treatment of disruptive behavior disorders in children and adolescents.  J Clin Psychiatry. 2008;69:(suppl 4)  9-14
PubMed   |  Link to Article
Aman MG, De Smedt G, Derivan A, Lyons B, Findling RL.Risperidone Disruptive Behavior Study Group.  Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence.  Am J Psychiatry. 2002;159(8):1337-1346
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PubMed   |  Link to Article
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PubMed   |  Link to Article
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Cates ME, Jackson CW, Feldman JM, Stimmel AE, Woolley TW. Metabolic consequences of using low-dose quetiapine for insomnia in psychiatric patients.  Community Ment Health J. 2009;45(4):251-254
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Philip NS, Mello K, Carpenter LL, Tyrka AR, Price LH. Patterns of quetiapine use in psychiatric inpatients: an examination of off-label use.  Ann Clin Psychiatry. 2008;20(1):15-20
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Daumit GL, Crum RM, Guallar E, Powe NR, Primm AB, Steinwachs DM, Ford DE. Outpatient prescriptions for atypical antipsychotics for African Americans, Hispanics, and whites in the United States.  Arch Gen Psychiatry. 2003;60(2):121-128
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Sohler NL, Walkup J, McAlpine D, Boyer C, Olfson M. Antipsychotic dosage at hospital discharge and outcomes among persons with schizophrenia.  Psychiatr Serv. 2003;54(9):1258-1263
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Mallinger JB, Fisher SG, Brown T, Lamberti JS. Racial disparities in the use of second-generation antipsychotics for the treatment of schizophrenia.  Psychiatr Serv. 2006;57(1):133-136
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Shi L, Ascher-Svanum H, Zhu B, Faries D, Montgomery WB, Marder SR. Characteristics and use patterns of patients taking first-generation depot antipsychotics or oral antipsychotics for schizophrenia.  Psychiatr Serv. 2007;58(4):482-488
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Kreyenbuhl J, Zito JM, Buchanan RW, Soeken KL, Lehman AF. Racial disparity in the pharmacological management of schizophrenia.  Schizophr Bull. 2003;29(2):183-193
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Depp C, Ojeda VD, Mastin W, Unützer J, Gilmer TP. Trends in use of antipsychotics and mood stabilizers among Medicaid beneficiaries with bipolar disorder, 2001-2004.  Psychiatr Serv. 2008;59(10):1169-1174
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Patel NC, DelBello MP, Keck PE Jr, Strakowski SM. Ethnic differences in maintenance antipsychotic prescription among adolescents with bipolar disorder.  J Child Adolesc Psychopharmacol. 2005;15(6):938-946
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McLeod JD, Pescosolido BA, Takeuchi DT, White TF. Public attitudes toward the use of psychiatric medications for children.  J Health Soc Behav. 2004;45(1):53-67
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Pescosolido BA, Perry BL, Martin JK, McLeod JD, Jensen PS. Stigmatizing attitudes and beliefs about treatment and psychiatric medications for children with mental illness.  Psychiatr Serv. 2007;58(5):613-618
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Pappadopulos E, Macintyre Ii JC, Crismon ML, Findling RL, Malone RP, Derivan A, Schooler N, Sikich L, Greenhill L, Schur SB, Felton CJ, Kranzler H, Rube DM, Sverd J, Finnerty M, Ketner S, Siennick SE, Jensen PS. Treatment recommendations for the use of antipsychotics for aggressive youth (TRAAY): part II.  J Am Acad Child Adolesc Psychiatry. 2003;42(2):145-161
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Coo H, Ouellette-Kuntz H, Lloyd JEV, Kasmara L, Holden JJ, Lewis ME. Trends in autism prevalence: diagnostic substitution revisited.  J Autism Dev Disord. 2008;38(6):1036-1046
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Correll CU, Kane JM. One-year incidence rates of tardive dyskinesia in children and adolescents treated with second-generation antipsychotics: a systematic review.  J Child Adolesc Psychopharmacol. 2007;17(5):647-656
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Frank RG, Garfield RL. Managed behavioral health care carve-outs: past performance and future prospects.  Annu Rev Public Health. 2007;28:303-320
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Appelbaum PS. The ‘quiet’ crisis in mental health services.  Health Aff (Millwood). 2003;22(5):110-116
PubMed   |  Link to Article
Mojtabai R, Olfson M. National trends in psychotherapy by office-based psychiatrists.  Arch Gen Psychiatry. 2008;65(8):962-970
PubMed   |  Link to Article
Mojtabai R. Americans' attitudes toward mental health treatment seeking: 1990-2003.  Psychiatr Serv. 2007;58(5):642-651
PubMed   |  Link to Article
Sernyak M, Rosenheck R. Experience of VA psychiatrist with pharmaceutical detailing of antipsychotic medications.  Psychiatr Serv. 2007;58(10):1292-1296
PubMed   |  Link to Article
Spielmans GI. The promotion of olanzapine in primary care: an examination of internal industry documents.  Soc Sci Med. 2009;69(1):14-20
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Li X, May RS, Tolbert LC, Jackson WT, Flournoy JM, Baxter LR. Risperidone and haloperidol augmentation of serotonin reuptake inhibitors in refractory obsessive-compulsive disorder: a crossover study.  J Clin Psychiatry. 2005;66(6):736-743
PubMed   |  Link to Article
Lorenz RA, Jackson CW, Saitz M. Adjunctive use of atypical antipsychotics for treatment-resistant generalized anxiety disorder.  Pharmacotherapy. 2010;30(9):942-951
PubMed   |  Link to Article
Findling RL. Dosing of atypical antipsychotics in children and adolescents.  Primary Care Companion J Clin Psychiatry. 2003;5:(suppl 6)  10-13http://www.psychiatrist.com/pcc/pccpdf/v05s06/v05s0603.pdf. Accessed February 18, 2012
Hartung DM, Wisdom JP, Pollack DA, Hamer AM, Haxby DG, Middleton L, McFarland BH. Patterns of atypical antipsychotic subtherapeutic dosing among Oregon Medicaid patients.  J Clin Psychiatry. 2008;69(10):1540-1547
PubMed   |  Link to Article
Buchanan RW, Kreyenbuhl J, Kelly DL, Noel JM, Boggs DL, Fischer BA, Himelhoch S, Fang B, Peterson E, Aquino PR, Keller W.Schizophrenia Patient Outcomes Research Team (PORT).  The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements.  Schizophr Bull. 2010;36(1):71-93
PubMed   |  Link to Article
 IMS Institute for Healthcare Informatics. The use of medicines in the United States: review of 2010. IMS website. http://www.imshealth.com/deployedfiles/imshealth/Global/Content/IMS%20Institute/Static%20File/IHII_UseOfMed_report.pdf. Accessed February 10, 2012

Figures

Tables

Table Graphic Jump LocationTable 1. Trends in National Annualized Population Estimates of Office-Based Physician Visits for Children, Adolescents, and Adults That Included Antipsychotic Treatmenta
Table Graphic Jump LocationTable 2. National Estimated Number of Office-Based Medical Visits by Children, Adolescents, and Adults That Included Antipsychotic Treatment (2005-2009)a
Table Graphic Jump LocationTable 3. Trends in Antipsychotic Prescribing Patterns in Youth and Adult Office-Based Visits, Stratified by Background Characteristics
Table Graphic Jump LocationTable 4. Trends in Antipsychotic Prescribing Patterns in Youth and Adult Office-Based Visits, Stratified by Clinical Characteristics
Table Graphic Jump LocationTable 5. Demographic and Clinical Characteristics of Office-Based Physician Visits With Antipsychotic Treatment by Child, Adolescent, and Adult, 2005-2009a
Table Graphic Jump LocationTable 6. Clinical Characteristics of Office-Based Physician Visits With Antipsychotic Treatment of Youths and Adults by Physician Specialty, 2005-2009a

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Olfson M, Blanco C, Liu SM, Wang S, Correll CU. National trends in the office-based treatment of children, adolescents, and adults with antipsychotics.. Arch Gen Psychiatry.. Published online August 6, 2012. doi:10.1001/archgenpsychiatry.2012.647.

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