JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 23, Number 9, 2013 ª Mary Ann Liebert, Inc. Pp. 620–627 DOI: 10.1089/cap.2013.0014

Polypharmacy Reduction in Youth in a Residential Treatment Center Leads to Positive Treatment Outcomes and Significant Cost Savings Pieter Joost van Wattum, MD, MA,1,2 Caroline Fabius, MA,1 Corey Roos, BA,1,3 Cheryl Smith, LCSW,1 and Todd Johnson, LCSW1

Abstract

Objective: The purpose of this study was to assess whether polypharmacy regimens can be safely and effectively reduced for youth placed in a residential treatment center, and to assess the cost savings achieved from medication reductions. Methods: Data were collected for 131 youth ages 11–18, who were admitted to and discharged from a residential treatment center between 2007 and 2011. Six month postdischarge data were available for 51 youth. Data include demographics, admission and discharge medications, place of discharge, and postdischarge stability level. Results: Upon admission, 30 youth were not on medication, at discharge 48 were not; a 60% increase. Mean number of admission medications was 2.16 (SD = 0.97) versus 1.55 (SD = 0.70) upon discharge. Upon admission, one youth was on five and nine were on four medications. At end-point, only one youth was on four medications. The number of youth needing two or more medications declined by 55%, and the number of those needing three or more declined by 69%. The largest reduction was seen in the number of antipsychotics and antidepressants. Mood stabilizer and antipsychotic combinations declined by 65%. Youth with medication reduction were more likely to be discharged to a less restrictive setting than were youth without medication reduction (72.6% vs. 53.8%), p = 0.03. At 6 months postdischarge, of the 51 out of 131 youth with available follow-up data, 71% were doing well. Cost analysis based on discontinued medication by class showed monthly savings of $21,365, or $256,368 yearly. The largest contributor was the reduction in the use of antipsychotics, accounting for $205,332 of the total savings. Conclusions: Our study indicates that comprehensive treatment can lead to significant reductions in polypharmacy, and positive short- and longer-term treatment outcomes. Judicial prescribing also resulted in significant cost reduction in an already costly healthcare system.

Introduction

D

uring the past two decades, the prevalence of psychotropic prescribing for children and adolescents with behavioral problems has significantly increased (Gadow 1997; Olfson et al. 2002; Safer et al. 2003; Zito et al. 2003; Cooper et al. 2004, 2006; Schubert et al. 2010; Pringsheim et al. 2011), more so in the United States and Canada than in other countries (Schirm et al. 2001; Zito et al. 2006, 2008a), with polypharmacy, the use of multiple psychotropic medications for one patient, becoming more the rule than the exception (Connor et al. 1997; Olfson et al. 2002; Safer et al. 2003; Zito et al. 2003; DosReis, et al. 2005; Cooper et al. 2006; Comer, et al. 2010). Co-prescription of second generation antipsychotic (SGA) medications in youth has become more commonplace, despite a lack of data supporting the safety and efficacy of polypharmacy (Greenhill et al. 2003; Safer et al. 2003; Correll 1 2 3

et al. 2006, 2007; Henin et al. 2009; Roke et al. 2009; Constantine et al. 2010). A longitudinal study of 1958 inpatients with bipolar disorder (Brooks et al. 2011) found that 10% of patients ‡15 years of age who were taking at least 1 SGA were prescribed more than one SGA. However, SGA polytherapy was associated with increased side effects, greater need for psychiatric and medical care, and no improved functioning. Moreover, a recent study (Essock et al. 2011) indicates that switching from antipsychotic polypharmacy to monotherapy was successful in two thirds of schizophrenic patients. In addition, the Combining Medications to Enhance Depression Outcomes (CO-MED) acute and long-term outcome study showed that by comparing two antidepressant combinations with monotherapy, no medication combination outperformed monotherapy (Rush et al. 2011). High rates of psychotropic medication use and polypharmacy is particularly found in youth in foster care and those placed in

The Children’s Center of Hamden, Hamden, Connecticut. Yale School of Medicine Child Study Center and Department of Psychiatry, New Haven, Connecticut. Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut.

620

OUTCOMES OF POLYPHARMACY REDUCTION IN YOUTH residential treatment centers (RTCs) (Connor et al. 1997; Gadow 1997; Zito et al. 2008b). Compared with less restrictive settings, RTCs serve youth who have significant emotional and behavioral problems, are victims of abuse and neglect, and frequently have a history of delinquent behavior (Duppong Hurley et al. 2009). These behavioral problems lead to a high risk for out-of-home placement, with youth frequently ending up in a trajectory of multiple placements (Breland-Noble et al. 2004; Connor and McLaughlin 2005; Handwerk et al. 2008). This track often leads to further deteriorating behavior and, consequently, an increase in the use of psychotropic medications to control these behaviors. In addition, the frequent moving around can lead to a lack of appropriate monitoring of adherence, efficacy, and continued need for these medications, as well as scattered psychosocial treatment. A study examining 83 youth consecutively admitted to a RTC, found that 76% of youths were taking psychotropic medications at admission, with 40% taking more than one medication (Connor et al. 1998). Another study reported an overall medication utilization rate of 49% among 1010 youths placed in a residential facility (Handwerk et al. 2008). These studies indicate that high numbers of youth in residential treatment receive one or more psychotropic medication, which, particularly in the case of polypharmacy, and considering the limited current knowledge about its efficacy, raises concerns about the safety and efficacy of psychopharmacotherapy for these seriously disturbed youth (Calarge et al. 2010). Few studies are available assessing medication reduction in a residential setting, and none in outpatient practice. Connor and McLaughlin (2005), in a retrospective analysis of 141 youth admitted and discharged from a RTC, assessing psychosocial factors and treatment outcomes related to medication reduction, found that, compared with admission, significantly more youth were discharged without medications, and significantly fewer youth were discharged on concurrent medications. Most importantly, medication reduction was correlated with diminishing psychopathology scores on the Devereux Scales of Mental Disorders, a 110 item rating scale to evaluate psychopathology in children. Another study retrospectively investigated medication reduction for 1010 youth receiving residential treatment. It found a significant reduction in utilization of medication from admission (40%) to departure (26%). Youth departing on no medication were more likely than those still on medications to be rated as more improved, and discharged to less restrictive postplacements (Handwerk et al. 2008). A case study of a youth admitted to an RTC on six medications demonstrated that medication change and reduction could be beneficial if decisions were made slowly, systematically, and based on behavioral data (Spellman et al. 2010). These results indicate that psychotropic medication reduction can be safely performed, and should be considered more frequently for youth placed in RTCs, and possibly incorporated into their treatment plan. The present study analyzed the data of 131 youth admitted and discharged from a residential treatment center between 2007 and 2011. The primary purpose of this study was to explore whether over the course of treatment for severely disturbed youth placed in an RTC, psychotropic medication regimens could be safely simplified (e.g., to once-daily dosing instead of twice or three-timesa-day dosing when not indicated), tapered, or discontinued. In addition, psychosocial variables related to medication use at admission were investigated. Six month postdischarge follow-up data were available for a large subgroup of our sample. Based on the current public discussion about the spiraling healthcare costs (Alexander et al. 2011) and considering recent findings that healthcare cost for youth is rising faster than for adults (Newman and Herrera 2012),

621 total monthly and yearly healthcare cost savings resulting from the medication reductions were estimated. Methods Sample Subjects in this study were 131 adolescents consecutively admitted to and discharged from an RTC (The Children’s Center of Hamden, CT) between July 1, 2007 and February 28, 2011. This accounts for 94% of the 140 adolescents who were referred to the Center in that period. Nine youth ran away or were removed and placed in higher levels of care before the admission process could be finished. The program serves seriously emotionally disturbed children and adolescents who are referred from the Department of Children and Families (DCF), other social services agencies, psychiatric hospitals, local boards of education, juvenile justice agencies, and parents. The program utilizes a treatment team approach, which includes child care workers, clinical therapists, nursing staff, a child psychiatrist, the child, family, and other stakeholders. Treatment plans are individualized for each youth in the program and designed to allow for the shortest length of stay possible. The majority of youth receive special education services in a highly structured, on-site school environment. Youth live in small groups in three separate cottages. Measures Upon admission, informed consent was obtained from parents and guardians of all youths included in this study. They were informed that data would be collected throughout the youth’s stay for research purposes and permission was asked to place a call for follow-up after discharge. Data were collected, stored, and analyzed in a way that secured maximum protection of confidentiality for each youth. Any changes in the medication regimen of youth were reviewed with the youth’s guardian, and consent and assent of the guardian and patient were obtained. The study was approved by the Institutional Review Board. An extensive chart review was conducted for all 131 youth, and data were retrieved from an archival electronic database by two raters from 2007 to 2011. Interrater reliability analysis was not available for this study. For this reason, historical and demographic variables were limited to those that could be objectively recorded from the chart by a rater. Complete medication data, demographic records, and clinical measures were available for 131 youth. Age at admission ranged from 11 to 18 years with an average age of 14.9 (SD = 1.49), 67% were male and 33% were female. Ethnic composition was: 35.9% Caucasian, 29% African-American, 25.2% Hispanic, and 9.9% other. Youth were referred from psychiatric hospitals (31.3%), detention centers (28.2%), other RTCs (14.5%), crisis stabilization programs (7.6%), emergency shelters (5.3%), foster homes (3.8%), group homes (3.1%), and bio-adoptive parents (5%). Each resident received an extensive psychiatric evaluation by the board certified child psychiatrist (P.J.v.W.) and diagnosed in accordance with the American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) (American Psychiatric Association 2000). Fifty-seven percent of youth received a diagnosis of mood disorder, 45% received a diagnosis of attention-deficit/hyperactivity disorder (ADHD), 39.7% received a diagnosis of an anxiety disorder, 37.4% received a diagnosis of conduct disorder, 34.4% received a diagnosis of oppositional defiant disorder, 10.7% received a diagnosis of psychotic disorders, and 6.9% received a diagnosis of personality disorder

622

VAN WATTUM ET AL.

traits. State protective services were involved with 93.1%, the juvenile justice system was involved with 3.8%, and the state was legal guardian for 67.9%. Sexual and physical abuse, multiple placements, and parental substance abuse were also assessed. These variables were only marked as present if there were explicit notes in the charts and records. Classes of medications assessed at admission and discharge included antidepressants (fluoxetine, sertraline, citalopram, escitalopram, fluvoxamine, bupropion, mirtazepine, venlafaxine), sleep aids (trazodone HCl, melatonin, clonidine, quetiapine), mood stabilizers (lithium, divalproic sodium, lamotrigine, oxcarbazepine, topiramate), antipsychotics (risperidone, paliperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, haloperidol, thorazine, molindone), ADHD medications (methylphenidate and amphetamine salt short acting and extended release preparations, clonidine, guanfacine, atomoxetine), and anti-enuretics (desmopressin). Principal psychiatric diagnoses at admission were retrieved from the initial evaluation conducted by the psychiatrist. For this study, DSM-IV-TR Axis I and II disorders were classified into seven groups: Anxiety disorders, mood disorders (depression, dysthymia, and bipolar disorders), personality disorder traits (antisocial and borderline personality disorder), psychotic disorders (schizophrenia, schizophreniform disorder, brief reactive psychoses, schizoaffective disorder), conduct disorder, oppositional defiant disorder, and ADHD. We used a modified version of the Restrictiveness of Living Environment Scale (Hawkins et al. 1992) to classify the postplacement of each youth into two simple categories: Highly restrictive and less restrictive The highly restrictive group included the following postplacements: County detention center, youth correctional facility, intensive treatment unit, medical or psychiatric hospital, and residential treatment center. The less restrictive group included the following postplacements: Group emergency center, group home, specialized foster care, regular foster care, adoptive home, home of biological parents, and independent living. Of the 96 successfully discharged youth, 85 were approached 6 months postdischarge for a follow-up phone interview; 11 subjects had not been discharged long enough at the conclusion of the study. We could not collect data for youth who had been discharged before completing treatment because they ran away, were placed in juvenile detention, or transferred to a higher level of care. Follow-up phone interviews were successfully conducted for 51 out of the 85 youth. Information was obtained about current place of residence,

as well as how many days in the last 6 months the youth ran away, had been truant, had been arrested, had damaged property, or had displayed self-harm. In addition, a score of overall well-being was obtained on a five point Likert scale: 0 (very poor), 1 (poor), 2 (okay), 3 (well), and 4 (very well). Finally, in order to explore the pharmaco-economical impact of medication reduction, the total combined monthly healthcare cost of psychotropic medications for the 101 youth on medication at admission and the 83 youth on medication at discharge was calculated. We also calculated the total combined monthly healthcare cost for youth whose dose was adjusted upwards or downwards or who received a medication regimen simplification. We used average drug prices as provided by drugstore.com. When available, prices of generic drugs were used instead of those for the name brand. Exact daily dosage and number of administrations per day were used when calculating cost. Data analyses IBM SPSS Version 19 (Armonk, NY) was used for data analysis. Descriptive statistics were calculated to examine demographics, medication evaluation at admission and discharge, cost reduction, and follow-up status. Chi-square analyses were used to assess changes in medication use from admission to discharge. Independent sample t tests or v2 analyses were used to compare youth on medication versus those not on medication at admission, as well as comparing youth who had a medication reduction during treatment versus those who did not. Pearson correlation coefficients and v2 analyses were calculated when necessary to examine the relationship of demographic and medical variables. Statistical significance was set at p £ 0.05. All tests were two tailed. Results Youth admitted on medication were more likely to be diagnosed with a mood disorder on admission than were those admitted on no medication, (64.4% versus 33.3%) (v2 [1, n = 131] = 9.1, p = 0.003). Length of stay was significantly longer for youth admitted on medication (mean = 298.4 days, SD = 198.3) compared with youth admitted on no medication (mean = 222.2 days, SD = 130.3); t (129) = -1.89; p = 0.050. There was no significant difference in number of admission medications for boys (mean = 2.20, SD = 0.99) versus girls (mean = 2.11, SD = 0.95); t(80) = - 0.35, p = 0.73. Similarly, there was no significant difference in number of

Table 1. Changes in Medication Usage from Admission to Discharge Medication usage Number of medicationsa At least 1 medication Concurrent medications (2 or more) Three or more medications Medication classb Antidepressants Mood stabilizers Antipsychotics ADHD Anti-enuretics Sleep aids a

Out of all 131 youth. Out of 101 youth admitted on medication. ***p £ 0.001. ADHD, attention-deficit/hyperactivity disorder. b

Admission n (%)

Discharge n (%)

v2

101 (77.1) 73 (55.7) 34 (26.0)

83 (63.4) 39 (29.8) 7 (5.3)

47.7*** 30.1*** 13.7***

24 16 52 32 2 2

27.3*** 30.4*** 20.2*** 54.1*** 49.5 32.3

42 30 79 44 4 6

(41.6) (29.7) (78.2) (43.6) (3.9) (5.9)

(23.8) (15.8) (51.5) (31.7) (2.0) (2.0)

OUTCOMES OF POLYPHARMACY REDUCTION IN YOUTH discharge medications for boys (mean = 1.53, SD = 0.72) versus girls (mean = 1.59, SD = 0.68); t (99) = 0.44, p = 0.66. Age on admission was not related to the number of medications on admission, r (101) = - 0.035, p = 0.73. Mean length of stay was 280.9 days (SD 187.23). Diagnostic comorbidity (diagnosis of more than two psychiatric disorders) was not related to gender v2 (1, n = 131) = 0.76, p = 0.38, taking medications at admission, v2 (1, n = 131) = 0.31, p = 0.58, medication reduction, v2 (1, n = 101) = 0.06, p = 0.81, dosage reduction, v2 (1, n = 101) = 0.53, p = 0.47, or level of posttreatment-placement, v2 (1, n = 123) = 0.001, p = 0.97. The mean total number of diagnoses at admission for youth was 2.73 (SD = 1.20). Total number of diagnoses was not significantly correlated with number of medications taken at admission, r (101) = - 0.02, p = 0.81, or length or stay, r (131) = 0.11, p = 0.19. Medication reduction Changes in the use of medication by number and class over the course of treatment are described in Table 1. As shown, from admission to discharge there were significant reductions in youth taking any medication, two or more medications, and three or more medications. The use of antidepressants was reduced by 40%, use of mood stabilizers was reduced by 46.7%, use of antipsychotics was reduced by 34.2%, and use of ADHD medications was reduced by 22.7%. On admission, 77.1% (n = 101) of all youth were taking psychotropic medication compared with 63.4% (n = 83) at discharge. Of the 30 youth not on medication when admitted, 27 were discharged without medication: One was started on an antidepressant, two on ADHD medication. Only 3.8% (n = 5) of 131 youth had an increase in the number of medications from admission to discharge. Mean number of admission medications was 2.16 (SD = 0.97) compared with 1.55 (SD = 0.70) discharge medications. For the 101 youth on medication, a reduction of three medications was seen in 8.9% (n = 9), a reduction of two was seen in 15.8% (n = 16), a reduction of one was seen in 36.6% (n = 37) and 36.6% (n = 37) had no change in medications, One percent (n = 1) had an increase of one medication, and 1% (n = 1) an increase of two medications. Therefore, 61.4% (n = 62) of the 101 youth admitted on medication had a reduction of one or more medications, whereas 20.7% (n = 21) of youth were taken off all medications (Fig. 1). In addition, 20 youth had a dose reduction for a least one medication. There was no difference in medication reduction between youth successfully discharged versus youth with an early, unplanned

FIG. 1. Change in number of youth prescribed medication from admission to discharge (n = 131).

623 discharge as a result of running away, placement in juvenile detention, or transfer to a higher level of care (0.96 vs. 1.0: NS). The number of youth taking multiple medications dropped significantly, from 72.3% (73 of 101) on admission to 38.6% (39 of 101) at discharge; a 46.6% reduction. On admission, six youth were taking two ADHD medications, at discharge only one (a stimulant and an a-agonist). Three youth were taking two mood stabilizers on admission. One was taking a mood stabilizer and two antipsychotics (lithium, thorazine, and aripiprazole), another was taking two antipsychotics (quetiapine, prescribed as sleep aid, and olanzapine) concurrently; on discharge no youth were taking either two mood stabilizers or antipsychotics concomitantly. The number of youth taking a combination of a mood stabilizer and an antipsychotic dropped from 26 at admission to 9 at discharge; a 65% decrease. Whereas reduction in or complete discontinuation of medication was frequent among our sample, the majority of youth (62.6%) were discharged on medication. Healthcare cost savings The total monthly cost of medications for the 101 youth on admission was $51,251 compared with $29,887 for the 83 youth on medication at discharge; a monthly saving of $21,364 from admission to discharge and a projected annual saving of $256,368. Further analyses of the monthly cost savings by medication class revealed savings of $502 for antidepressants, $2,903 for mood stabilizers, $17,111 for antipsychotics, $714 for ADHD medications, $26 for sleep aids, and $109 for anti-enuretics. Among the 101 youth taking medication at admission, 20 had only dose reductions or simplifications (e.g., q.a.m. instead of b.i.d. dosing) accounting for a monthly saving of $4,834 ($14,698 on admission: $9,874 at discharge), or $58,008 on an annual basis. Psychosocial characteristics and medication reduction Table 2 presents a comparison of youth with or without medication reductions during treatment. Compared with youth admitted on only one medication, youth admitted on multiple medications were more likely to have medication reductions (82.3% vs. 56.4%) (v2 [1, n = 101] = 7.98, p = 0.005. Youth on antidepressants were more likely to have medication reductions than were youth on other medication classes, (51.6% vs. 25.6%) (v2 (1, n = 101) = 6.65, p = 0.01), as did youth on mood stabilizers (40.3% vs. 12.8%) (v2 [1, n = 101] = 8.67, p = 0.003). Treatment outcome Youth with medication reduction were more likely to be discharged to a less restrictive setting than were youth without medication reduction (72.6% vs. 53.8%), v2 (1, n = 95) = 4.62, p = 0.03 (see Table 3 for places of discharge). The majority of youth were discharged to a less restrictive setting. There were no significant differences in mean number of discharge medications between youth discharged to highly restrictive (mean = 1.69, SD = 0.88) versus those discharged to less restrictive settings (mean = 1.44, SD = 0.60) t (76) = 1.46, p = 0.15. Thirteen youth ran away and were discharged after an inability to trace them. However, for 10 of these youth, no change in medications was made, and 3 received a reduction in medication. Youth discharged to less restrictive postplacements had a significantly longer length of stay (mean = 335.75 days; SD = 194.31) than did youth discharged to highly restrictive postplacements (mean = 181.85 days; SD = 140.72) t (114) = - 4.21, p = 0.001.

624

VAN WATTUM ET AL. Table 3. Postdischarge Placements (n = 123)a

Table 2. Comparison of Youth with Change in Medication versus those with No Change in Medicationa

ROLES setting

n (%)

n (%) or mean – SD

Characteristicb

Medication reduced (n = 62)

No change (n = 39)

v2 or t (df)c

Demographics Sex 0.22 Male 41 (66.1) 24 (61.5) Female 21 (33.9) 15 (38.5) Age at admission 14.8 – 1.58 14.8 – 1.50 - 0.06 (99) Race 0.75 White 26 (41.9) 13 (33.3) Non-white 36 (58.1) 26 (66.7) Number of diagnoses 2.53 – 1.18 2.97 – 1.30 1.74 (99) Mood disorder 39 (62.9) 26 (66.7) 0.15 Anxiety disorder 23 (37.1) 17 (43.6) 0.42 ADHD 25 (40.3) 17 (43.6) 0.11 Personality disorder 5 (8.1) 1 (2.6) 1.29 traits Psychotic disorders 8 (12.9) 5 (12.8) 0.00 Conduct disorder 17 (27.4) 17 (43.6) 2.80 Oppositional defiant 17 (27.4) 16 (41.0) 2.02 disorder Medication use at admission Concurrent medications 51 (82.3) 22 (56.4) 7.98** Antipsychotics 50 (80.6) 29 (74.4) 0.55 Antidepressants 32 (51.6) 10 (25.6) 6.65** Mood stabilizers 25 (40.3) 5 (12.8) 8.67** ADHD medications 27 (43.5) 17 (43.6) 0.00 Other relevant history Sexual/physical abuse 43 (69.4) 26 (66.7) 0.08 Multiple placements 46 (74.2) 25 (64.1) 1.91 Parental substance 32 (51.6) 22 (56.4) 0.40 abuse history Treatment variables Length of stay (days) 319.9 – 162.1 264.1 – 243.5 - 1.38 (99) ROLES postplacement 4.62* setting Highly restrictive 13 (30.0) 16 (41.0) Less restrictive 45 (72.6) 21 (53.8) a

Out of 101 youth admitted on medication. For dichotomous variables, n (%) is reported; for continuous variables, mean – standard deviation. c 2 v test for dichotomous variables; t test for continuous variables. *p £ 0.05*; **p £ 0.01. ADHD, attention-deficit/hyperactivity disorder; ROLES, restrictiveness of living environment scale. b

Six month follow-up data were obtained for 51 of the 131 youth. Of these, 46 (90%) were residing in less restrictive settings: 34 (66.7%) with parents or grandparents, 11 (21.6%) in a group home, and 1 (2%) was living independently. Five (10%) were residing in highly restrictive settings: Three (6%) in an RTC, and one (2%) in an emergency shelter; one (2%) was hospitalized. Thirty-nine youth (77%) were living in the same setting that they were discharged to; 12 (23%) were residing in a different setting. Results also revealed that 16% (n = 8) were doing very well, 52% (n = 28) were doing well, 20% (n = 9) were ‘‘okay,’’ 8% (n = 4) were doing poorly, and 4% (n = 2) were doing very poorly. Among the five youth residing in highly restrictive settings, one was rated as doing very poorly, two were rated as doing poorly, one was rated as

Highly restrictive (n = 38, 30.9%) Detention center Youth correctional facility Hospital Residential treatment center Intensive treatment unit Less restrictive (n = 85, 69.1%) Group emergency shelter Group home Specialized foster care Regular foster care Adoptive home Home of biological parents Independent living

18 1 7 11 1

(14.6) (0.8) (5.7) (8.9) (0.8)

1 24 2 3 3 48 4

(0.8) (19.5) (1.6) (2.4) (2.4) (39.0) (3.3)

a

Placement setting data for 8 out of 131 youth were missing. ROLES, restrictiveness of living environment scale.

‘‘okay,’’ and one was rated as doing very well. Of these five, two youth had no change in medication from admission to discharge, one youth had a decrease of one medication, one had a decrease of two medications, and one had a decrease of three medications. The youth rated as doing very well had a decrease of three medications; one youth rated as doing poorly had a decrease of two medications. Medication reduction was not related to level of postplacement at 6 months, v2 (1, n = 51) = 0.27, p = 0.61, or to being arrested after discharge (six youth were arrested after discharge), v2 (1, n = 51) = 0.003, p = 0.96. There were no significant differences between youth whose medications were reduced versus those whose medications were not reduced on overall functioning score (t [49] = -1.58, p = 0.12), assaultive behavior (t [49] = - 0.78, p = 0.46), running away (t [48] = - 0.57, p = 0.56), damaging property (t [48] = -1.11, p = 0.27), truancy (t [48] = 0.98, p = 0.33), or self-injurious behavior (t [48] = 0.96, p = 0.34) during the 6 months after discharge. Discussion The aim of the present study was to assess whether for youth placed in a residential treatment center, polypharmacy regimens can be safely and effectively reduced without a negative effect on treatment outcome. Secondary aim was to assess the cost savings achieved through the medication reductions. The results showed significant reductions in polypharmacy, a positive treatment outcome, and a resulting substantial reduction in the cost of medication. Sixty percent of all youth admitted on medication had a reduction of at least one medication, 22% of youth admitted on medication were discharged without medication, and the number of youth receiving polypharmacy upon admission dropped from 73 to 39 at discharge, a 47% decrease. Reductions occurred among all classes of medications, but were largest for mood stabilizers and antipsychotics. The latter are increasingly prescribed for a variety of disorders (Alexander et al. 2011). A recent study showed a small decline in the rate of psychotropic polypharmacy for children in foster care, but the use of antipsychotics continued to increase (Rubin et al. 2012). However, this may in part be because most atypical antipsychotics are now approved and marketed for bipolar disorder in adolescents, replacing the older mood stabilizing agents such as lithium and valproic acid, for which a decrease in use was

OUTCOMES OF POLYPHARMACY REDUCTION IN YOUTH found. Our study shows that even for severely disturbed youth, comprehensive treatment may lead to significant improvement and successful medication reduction or discontinuation across all medication categories. Our findings are consistent with earlier reports (Connor and McLaughlin 2005; Handwerk et al. 2008). However, we found higher rates of polypharmacy reduction, which is likely because these studies were retrospective chart reviews, and ours is a prospective study with the intent to pursue a reduction in the use of psychopharmacotherapy, and in polypharmacy in particular. During the course of treatment, concerted efforts were made to address emerging internalizing or externalizing behaviors with psychotherapy or other behavior modification interventions rather than pharmacological intervention. Pro re nata medication was never allowed. Our follow-up data indicate that pharmacotherapy reduction or discontinuation, when performed judicially, does not lead to significant deterioration in behaviors, with 77% of youth still doing well at 6 months after discharge, whereas youth with medication reduction were more likely to be discharged to a less restrictive setting than were youth whose medications were unchanged. In addition, outcome for youth admitted for a longer period of time was better than those with a short stay, likely indicating that they benefitted from the extended intensive treatment. In recent years, multiple studies have been published assessing the increase in polypharmacy in youth, but data were mostly obtained from large (Medicaid) pharmacy records using the numbers of prescriptions written (Zito et al. 2003; Safer et al. 2004 DosReis et al. 2005). However, this does not allow for assessment of adherence to treatment, and hence efficacy of the medication. Nonadherence occurs frequently (Dean et al. 2011). It is often ignored by prescribers and may be a reason for treatment failure, and the large amounts of unused medication lead to a loss of healthcare dollars (Sabate 2003; Sokol et al. 2005). One strength of our study is the fact that medications were given by nurses and medicationcertified staff. Medication refusal was discussed as part of the treatment plan through education, and frequently seen as an opportunity to assess whether the medication could be discontinued or lowered in dosage, or whether it should be continued. This study assessed overprescribing and irrational polypharmacy. However, polypharmacy may be needed and can be practiced in a rational manner. An example of rational use of polypharmacy may be a child with ADHD, significantly improved on a long-acting medication such as guanfacine extended release, but still displaying difficulty concentrating in school, who receives a (low) dose of a stimulant medication during school days. Another example is a child with bipolar disorder and comorbid ADHD who receives a mood stabilizer and a stimulant medication. Practicing rational and evidence-based use of pharmacotherapy can be challenging. In our treatment center, we encountered significant resistance from staff, family members, and other caregivers who had at firsthand experienced the frequent and long-term aggressive behaviors from the patients in their care, and saw medication as the only helpful treatment modality. This was addressed by repeated, extensive education about the potential benefits, limitations, and (long-term) side effects of medications, as well as teaching alternative ways to avoid or curb unwanted behaviors through in-service seminars. Similarly, patients and their caregivers were educated about the benefits and limitations of pharmacotherapy as well as possible alternative treatments. At our center, treatment team meetings are held once a month at a minimum, and attended by the patient, clinician, cottage staff, school staff, guardians/caregivers, the psychiatrist, and other stakeholders. In

625 these meetings, adjustments in the treatment plan and the potential benefits are discussed and agreed upon by all. Environmental triggers for behaviors are noted and evaluated, and ways to address them are discussed. Specific behavioral plans are emphasized; for example, a behavior plan for enuretic patients can lead to quick changes, and enuretics were in general no longer needed. Similarly, sleep was monitored by staff if sleep medication was prescribed or requested, leading to discontinuation of most sleep aids. Family therapy occurs at a minimum on a weekly basis for each resident, as does group therapy. Individual psychotherapy, supportive (trauma-focused) cognitive behavioral, interpersonal, and dialectical behavioral therapy are all used where indicated by trained clinicians. A young adult program was started for older residents who had made significant progress. Its aim is to prepare residents for integration into the community by providing assistance in, for example, navigating public transportation and banking. A new kitchen garden project has helped teach healthy eating habits. These programs are popular with residents and encourage positive behaviors, needed to be enrolled. An on-site work program for residents ‡14 years of age, including jobs in maintenance, the kitchen, and the grounds, keeping allows for acquiring work skills while the possibility of earning money incentivizes positive behavior changes and helps teach budgeting. The response to pilot data from this study presented at annual meetings of professional organizations convinced administrators and led to their full support. After observing positive outcome, a clear change in attitude toward the use of medication was noticeable in all involved, which further enhanced our efforts to curb irrational prescribing. The cost of prescribing is seldom considered by physicians unless they are reminded by an insurance company’s prior authorization request. Many physicians are unaware of the (approximate) cost of a particular medication (Bellian et al. 2001; Allan et al. 2007), and few medical schools include seminars on (the physician’s role in) healthcare expenditures in their curricula. Prescription decisions made based on medication prices, in particular the assumption that generic medications are always cheaper than brand name medications, are often unfounded, as prices vary by insurance or pharmacy. For example, we found that one month’s supply of risperidone was not much cheaper than Risperdal (drugs.com). Although our first priority was good clinical outcome, our secondary aim of cost containment proved effective as well considering the projected large amount of money saved. Simplification of medication regimens, for example, eliminating twice-daily dosing based on known pharmacokinetics, pharmacodynamics, and clinical observation did not need reversal in any of our patients, and most of these simplifications were made on the day of or in the first week after admission. This approach alone can often cut the per-patient medication expense in half. Not included in the projected savings are annual cost of medication checks, including recommended blood monitoring, or the long-term cost related to medication side effects such weight gain, diabetes mellitus, hypercholesterolemia, and coronary artery disease. Despite the significant reduction in the use of (poly)pharmacotherapy, the majority of youth (80 out of 101) admitted on medication were discharged on medication, and 3 of the 30 who were admitted on no medication were started on a medication trial, indicating that medication plays an important role in treating youth with psychiatric disorders. However, the fact that only 3 of the 30 youth not on medication needed a medication trial also indicates that pharmacotherapy is not indicated for every youth presenting

626 with significant behavioral disturbance. For many youth, psychosocial treatment alone may be beneficial. Limitations This study has several limitations. There was no control group in this study: Randomization to active treatment and control would not only be difficult to achieve but also ethically not justifiable. Admission diagnoses were often made based on incomplete information. For many of the admitted youth there were no reliable informants, or a paper trail of their usually long history of treatment was lacking. Hence, it was often not clear why youth had been prescribed (multiple) medications. The prescribing child psychiatrist used best and evidence based practices in assessing when and how to change medications. The type of treatment setting for our study may not allow for (full) generalization of our findings. However, many of the medication changes, such as dosage schedule simplification or dosage reduction, were made upon admission or within the first few days to weeks after admission, respectively, in general without negative effects. Conclusions During the past two decades, psychotropic prescribing for children and adolescents with behavioral problems has significantly increased, with polypharmacy becoming more the rule than the exception. The multiple studies published assessing this increase mostly obtained data from (Medicaid) pharmacy records, using numbers of prescriptions written, hence not allowing for assessment of adherence to and efficacy of the medication. No studies are available assessing medication reduction in outpatient settings, and only a few are available assessing medication reduction in residential settings. This prospective study explored whether psychotropic medication regimens could be safely simplified, tapered, or discontinued over the course of treatment among youth in a residential treatment center. Six month postdischarge follow-up data were presented for a large subgroup of our sample. The results show that polypharmacy can safely be reduced and lead to a positive treatment outcome, continued after discharge, and as a result, to significant cost savings. Clinical Significance Our study shows that, in conjunction with comprehensive psychosocial treatment, judicious prescribing can lead to significant reduction in polypharmacy and pharmacotherapy in general, with the majority of successfully discharged youth still doing well at 6 month follow-up. Our study indicates that careful prescribing is beneficial to patients and can lead to significant cost reduction in an already costly healthcare system. Disclosures No competing financial interests exist. References Alexander GC, Gallagher SA, Mascola A, Moloney RM, Stafford RS: Increasing off-label use of antipsychotic medications in the United States, 1995-2008. Pharmacoepidemiol Drug Saf 20:177–184, 2011. Allan GM, Lexchin J, Wiebe N: Physician awareness of drug cost: A systematic review. Plos Med 4:e283, 2007. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North Ameri-

VAN WATTUM ET AL. can Association for the Study of Obesity: Consensus development conference on antipsychotic drugs and obesity and diabetes. J Clin Psychiatry 65:267–272, 2004. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision. Washington, DC: American Psychiatric Association; 2000. Bellian DP, King KA, Wahl J, Price JH: Psychiatrists’ knowledge and attitudes about costs of commonly prescribed treatments in psychiatry. J Community Health 26:11–22, 2001. Breland–Noble AM, Elbogen EB, Farmer EM, Dubs MS, Wagner HR, Burns BJ: Use of psychotropic medications by youths in therapeutic foster care and group homes. Psychiatr Serv 55:706–708, 2004. Brooks JO, 3rd, Goldberg JF, Ketter TA, Miklowitz DJ, Calabrese JR, Bowden CL, Thase ME: Safety and tolerability associated with second-generation antipsychotic polytherapy in bipolar disorder: Findings from the Systematic Treatment Enhancement Program for Bipolar Disorder. J Clin Psychiatry 72:240–247, 2011. Calarge CA, Zimmerman B, Xie D, Kuperman S, Schlechte JA: A cross-sectional evaluation of the effect of risperidone and selective serotonin reuptake inhibitors on bone mineral density in boys. J Clin Psychiatry 71:338–347, 2010. Comer JS, Olfson M, Mojtabai R: National trends in child and adolescent psychotropic polypharmacy in office-based practice, 1996–2007. J Am Acad Child Adolesc Psychiatry 49:1001–1010, 2010. Connor DF, McLaughlin TJ: A naturalistic study of medication reduction in a residential treatment setting. J Child Adolesc Psychopharmacol 15:302–310, 2005. Connor DF, Ozbayrak KR, Harrison RJ, Melloni RH, Jr: Prevalence and patterns of psychotropic and anticonvulsant medication use in children and adolescents referred to residential treatment. J Child Adolesc Psychopharmacol 8:27–38, 1998. Connor DF, Ozbayrak KR, Kusiak KA, Caponi AB, Melloni RH, Jr: Combined pharmacotherapy in children and adolescents in a residential treatment center. J Am Acad Child Adolesc Psychiatry 36:248–254, 1997. Constantine RJ, Boaz T, Tandon R: Antipsychotic polypharmacy in the treatment of children and adolescents in the fee-for-service component of a large state Medicaid program. Clin Ther 32:949– 959, 2010. Cooper WO, Arbogast PG, Ding H, Hickson GB, Fuchs DC, Ray WA: Trends in prescribing of antipsychotic medications for US children. Ambul Pediatr 6:79–83, 2006. Cooper WO, Hickson GB, Fuchs C, Arbogast PG, Ray WA: New users of antipsychotic medications among children enrolled in TennCare. Arch Pediatr Adolesc Med 158:753–759, 2004. Correll CU, Frederickson AM, Kane JM, Manu P: Does antipsychotic polypharmacy increase the risk for metabolic syndrome? Schizophr Res 89:91–100, 2007. Correll CU, Penzner JB, Parikh UH, Mughal T, Javed T, Carbon M, Malhotra AK: Recognizing and monitoring adverse events of second-generation antipsychotics in children and adolescents. Child Adolesc Psychiatr Clin N Am 15:177–206, 2006. Dean AJ, Wragg J, Draper J, McDermott BM: Predictors of medication adherence in children receiving psychotropic medication. J Paediatr Child Health 47:350–355, 2011. DosReis S, Zito JM, Safer DJ, Gardner JF, Puccia KB, Owens PL: Multiple psychotropic medication use for youths: a two-state comparison. J Child Adolesc Psychopharmacol 15:68–77, 2005. Duppong Hurley K, Trout A, Chmelka B, Burns BJ, Epstein M, Thompson R, Daley DL: The changing mental health needs of youth admitted to residential group home care: Comparing mental health status at admission in 1995 and 2004. J Emot Behav Disord 17:164– 176, 2009.

OUTCOMES OF POLYPHARMACY REDUCTION IN YOUTH Essock SM, Schooler NR, Stroup TS, McEvoy JP, Rojas I, Jackson C, Covell NH: Effectiveness of switching from antipsychotic polypharmacy to monotherapy. Am J Psychiatry 168:702–708, 2011. Gadow KD: An overview of three decades of research in pediatric psychopharmacoepidemiology. J Child Adolesc Psychopharmacol 7:219–236, 1997. Greenhill LL, Vitiello B, Riddle MA, Fisher P, Shockey E, March JS, Levine J, Fried J, Abikoff H, Zito JM, McCracken JT, Findling RL, Robinson J, Cooper TB, Davies M, Varipatis E, Labellarte MJ, Scahill L, Walkup JT, Capasso L, Rosengarten J: Review of safety assessment methods used in pediatric psychopharmacology. J Am Acad Child Adolesc Psychiatry 42:627–633, 2003. Handwerk ML, Smith GL, Thompson RW, Spellman DF, Daly DL: Psychotropic medication utilization at a group-home residential facility for children and adolescents. J Child Adolesc Psychopharmacol 18:517–525, 2008. Hawkins RP, Almeida MC, Fabry B, Reitz AL: A scale to measure restrictiveness of living environments for troubled children and youths. Hosp Community Psychiatry 43:54–58, 1992. Henin A, Mick E, Biederman J, Fried R, Hirshfeld–Becker DR, Micco JA, Miller KG, Rycyna CC, Wozniak J: Is psychopharmacologic treatment associated with neuropsychological deficits in bipolar youth? J Clin Psychiatry 70:1178–1185, 2009. Newman D, Herrera C: Children’s Health Care Spending Report. Washington, DC: Health Care Cost Institute, Inc; 2012. Olfson M, Marcus SC, Weissman MM, Jensen PS: National trends in the use of psychotropic medications by children. J Am Acad Child Adolesc Psychiatry 41:514–521, 2002. Pringsheim T, Lam D, Patten SB: The pharmacoepidemiology of antipsychotic medications for Canadian children and adolescents: 2005–2009. J Child Adolesc Psychopharmacol 21:537–543, 2011. Roke Y, van Harten PN, Boot AM, Buitelaar JK: Antipsychotic medication in children and adolescents: A descriptive review of the effects on prolactin level and associated side effects. J Child Adolesc Psychopharmacol 19:403–414, 2009. Rubin D, Matone M, Huang YS, dosReis S, Feudtner C, Localio R: Interstate variation in trends in psychotropic medication use among Medicaid-children enrolled in foster care. Child Youth Serv Rev 34:1492–1499, 2012. Rush AJ, Trivedi MH, Stewart JW, Nierenberg AA, Fava M, Kurian BT, Warden D, Morris DW, Luther JF, Husain MM, Cook IA, Shelton RC, Lesser IM, Kornstein SG, Wisniewski SR: Combining medications to enhance depression outcomes (CO-MED): Acute and long-term outcomes of a single-blind randomized study. Am J Psychiatry 168:689–701, 2011.

627 Sabate E: Adherence to Long-Term Therapies: Evidence for Action. Geneva: World Health Organization; 2003. Safer DJ, Zito JM, DosReis S: Concomitant psychotropic medication for youths. Am J Psychiatry 160:438–449, 2003. Safer DJ, Zito JM, Gardner JF: Comparative prevalence of psychotropic medications among youths enrolled in the SCHIP and privately insured youths. Psychiatr Serv 55:1049–1051, 2004. Schirm E, Tobi H, Zito JM, de Jong-van den Berg LT: Psychotropic medication in children: A study from the Netherlands. Pediatrics 108:E25, 2001. Schubert I, Koster I, Lehmkuhl G: The changing prevalence of attention-deficit/hyperactivity disorder and methylphenidate prescriptions: a study of data from a random sample of insurees of the AOK Health Insurance Company in the German State of Hesse, 2000–2007. Dtsch Arztebl Int 107:615–621, 2010. Sokol MC, McGuigan KA, Verbrugge RR, Epstein RS: Impact of medication adherence on hospitalization risk and healthcare cost. Med Care 43:521–530, 2005. Spellman DF, Griffith AK, Huefner JC, Wise N, 3rd, McElderry E, Leslie LK: Psychotropic medication management in a residential group care program. Child Welfare 89:151–167, 2010. Zito JM, Safer DJ, de Jong-van den Berg LT, Janhsen K, Fegert JM, Gardner JF, Glaeske G, Valluri SC: A three-country comparison of psychotropic medication prevalence in youth. Child Adolesc Psychiatry Ment Health 2:26, 2008a. Zito JM, Safer DJ, DosReis S, Gardner JF, Magder L, Soeken K, Boles M, Lynch F, Riddle MA: Psychotropic practice patterns for youth: A 10-year perspective. Arch Pediatr Adolesc Med 157:17–25, 2003. Zito JM, Safer DJ, Sai D, Gardner JF, Thomas D, Coombes P, Dubowski M, Mendez–Lewis M: Psychotropic medication patterns among youth in foster care. Pediatrics 121:e157–163, 2008b. Zito JM, Tobi H, de Jong-van den Berg LT, Fegert JM, Safer DJ, Janhsen K, Hansen DG, Gardner JF, Glaeske G: Antidepressant prevalence for youths: A multi-national comparison. Pharmacoepidemiol Drug Saf 15:793–798, 2006.

Address correspondence to: Pieter Joost van Wattum, MD, MA The Children’s Center of Hamden 1400 Whitney Avenue Hamden, CT, 06517 E-mail: [email protected]