Abstract
This study investigates differences in the characteristics of US youths treated with psychotropic polypharmacy and in the psychotropic classes used in combination.
The use of medication from 2 or more psychotropic classes, ie, polypharmacy,1 has increased among US youths2 despite limited evidence of efficacy and mounting safety concerns.3 The US Food and Drug Administration (FDA) approved several psychotropic classes, eg, selective serotonin reuptake inhibitors and second-generation antipsychotics, for expanded use in pediatric populations,4,5 but it is unknown whether this corresponds with the observed increase in psychotropic polypharmacy and who is more likely to receive psychotropic polypharmacy. Our goal was to investigate differences during a 17-year study period in the characteristics of US youths treated with psychotropic polypharmacy and in the psychotropic classes used in combination.
Methods
This is a cross-sectional study using the Medical Expenditure Panel Survey (MEPS) data from 1999 to 2015. The MEPS is a national household survey that generates sampling weights to obtain nationally representative estimates on health care use and expenditures in the United States. Sampling design and weighting details are described elsewhere.6 The study included youths younger than 18 years who reported psychotropic polypharmacy. Each study year consists of 3 interview rounds. To define psychotropic polypharmacy in a study year, 3 or more psychotropic classes must be reported together in at least 1 of the 3 interview rounds in the year. Our definition identified psychotropic classes taken together and avoided the capture of clinically recommended 2-class regimens (ie, use of α-agonists with stimulants). We used the American Hospital Formulary System to categorize medications by psychotropic class: stimulants, antidepressants, mood stabilizers, antipsychotics, anxiolytics/hypnotics, sedatives, and α-agonists. Atomoxetine was included in the stimulant class because this is a second-line treatment for attention-deficit/hyperactivity disorder (ADHD). The study received an exemption as non–human participants research from the University of Maryland institutional review board. We used publicly available data; therefore, no patient consent was needed in our study.
Individual study years were pooled into 3 periods (1999-2004, 2005-2010, and 2011-2015). We examined youth characteristics (age, sex, race/ethnicity, individual psychotropic class use, and psychiatric disorders) and the psychotropic polypharmacy combinations in each period. Weighted frequency analysis obtained nationally representative estimates and 95% confidence intervals in each period. Separate crude weighted logistic regression models were used to compare youth characteristics between adjacent periods. All raw sample sizes met the MEPS reporting standard. A domain analysis was conducted for subgroup analyses.
Results
Table 1 shows the number of US youths treated with psychotropic polypharmacy increased from 101 836 (1999-2004) to 222 955 (2005-2010) to 293 492 (2011-2015). Youths who were male and White composed the largest proportion in all periods. The proportion who were age 13 to 18 years increased significantly from 2005 through 2010 to 2011 through 2015 (17.2%; 95% CI, 16.9%-17.5%). In 1999 to 2004, the most common psychotropic classes were stimulants/atomoxetine (77.8%), antidepressants (71.3%), and mood stabilizers (61.2%). In the subsequent periods, stimulants/atomoxetine remained the predominant class. Antipsychotics significantly increased 30.7% (95% CI, 30.0%-31.4%) from 1999 through 2004 to 2005 through 2010, while the modest increase from 2005 through 2010 to 2011 through 2015 was not significant. We observed a significant decrease of 20.6% (95% CI, 20.2%-21.0%) in mood stabilizers from 1999 through 2004 to 2005 through 2010 followed by a nonsignificant decrease from 2005 through 2010 to 2011 through 2015. More than 80% of US youths with reported psychotropic polypharmacy had an ADHD diagnosis. There was a 10.1% (95% CI, 9.9%-10.3%) increase from 2005 through 2010 to 2011 through 2015 in the proportion who had 3 or more documented diagnoses.
Table 1. Demographic and Clinical Characteristics of Youth Treated With Psychotropic Polypharmacy From 1999-2015.
| Characteristic | Weighted % (95% CI)a | ||
|---|---|---|---|
| 1999-2004 (Weighted n = 101 836; unweighted n = 98) | 2005-2010 (Weighted n = 222 955; unweighted n = 158) | 2011-2015 (Weighted n = 293 492; unweighted n = 209) | |
| Age, y | |||
| 0-4 | NAb | NAb | 1.3 (0-3.4) |
| 5-12 | 51.5 (37.3-65.8) | 52.3 (42.0-62.6) | 33.8 (25.0-42.6) |
| 13-18 | 48.5 (34.2-62.7) | 47.7 (37.4-58.0) | 64.9 (55.6-74.1) |
| Sex | |||
| Male | 69.2 (59.9-81.4) | 75.6 (65.0-86.2) | 64.0 (52.0-76.0) |
| Female | 30.8 (18.6-43.1) | 24.4 (13.8-35.0) | 36.0 (24.0-48.5) |
| Race/ethnicity | |||
| Non-Hispanic | |||
| White | 80.9 (72.0-90.0) | 79.5 (72.0-87.1) | 70.7 (62.4-79.1) |
| Black | 6.6 (1.3-12.0) | 8.7 (4.1-13.3) | 12.6 (6.0-19.1) |
| Hispanic and other | 3.8 (5.0-20.0) | 11.8 (5.3-18.3) | 16.7 (10.4-22.9) |
| Psychotropic classes | |||
| Antipsychotics | 38.3 (25.2-51.5) | 69.0 (59.2-78.8) | 75.6 (65.4-85.7) |
| Antidepressants | 71.3 (59.7-83.0) | 62.7 (51.5-74.0) | 64.2 (53.5-74.9) |
| Stimulants/atomoxetine | 77.8 (66.2-89.5) | 82.1 (72.2-91.9) | 78.1 (68.5-87.6) |
| Sedatives/anxiolytics | 21.8 (9.8-33.7) | 13.5 (4.8-22.1) | 15.7 (6.9-24.5) |
| α-Agonistsc | 48.6 (34.6-62.5) | 48.5 (37.1-59.9) | 62.1 (51.3-72.9) |
| Mood stabilizers | 61.2 (47.7-74.7) | 40.6 (30.4-50.9) | 37.98 (27.4-48.6) |
| No. of psychiatric diagnoses | |||
| 0-1 | Not evaluabled | 42.2 (31.4-53.9) | 22.3 (13.0-31.6) |
| 2 | 52.6 (42.1-63.2) | 62.4 (52.5-72.3) | |
| ≥3 | 5.2 (0.1-10.3) | 15.3 (8.1-22.5) | |
| Psychiatric diagnosis | |||
| ADHD | 81.4 (72.2-90.5) | 85.2 (76.3-94.1) | |
| Mood disordere | 48.6 (38.2-59.0) | 60.0 (50.2-69.9) | |
| Schizophrenia | 3.7 (0-7.7) | 1.0 (0-2.9) | |
| Adjustment disorder | 0.4 (0-1.3) | 0.3 (0-0.9) | |
| Development disorder | NAb | 5.1 (1.1-9.1) | |
| Anxiety disorder | 25.3 (14.9-35,7) | 38.6 (27.3-49.8) | |
| Autism and otherf | 19.7 (9.4-29.9) | 26.9 (16.6-37.2) | |
| Otherg | 6.3 (1.2-11.4) | 14.4 (6.4-22.4) | |
Abbreviation: ADHD, attention-deficit/hyperactivity disorder; NA, not applicable.
Weighted proportions were reported as nationally representative estimates of youth characteristics in each period.
NA indicates that the sample did not capture any events in corresponding cells.
Included guanfacine and clonidine.
Psychiatric diagnoses were not reported in 1999 to 2004 as surveyed medical conditions were not comparable to those in other years.
Included depressive disorder and bipolar disorder.
Included autism, elimination disorders, tic disorders, and other mental disorders diagnosed in infants, children, and adolescents.
Included personality disorder, substance use disorder, alcohol use disorder, and other miscellaneous psychiatric disorders.
Table 2 shows the psychotropic class combinations reported in 10% or more of youths who received psychotropic polypharmacy. Stimulants were present in nearly all regimens, and antipsychotics became prominent in combinations after 2004.
Table 2. The Most Frequently Prescribed Psychotropic Polypharmacy Patterns Among Youths Treated With Psychotropic Polypharmacya.
| Polypharmacy combinations | Weighted % (95% CI) |
|---|---|
| 1999-2004 | |
| Atd, Sti, Msb | 17.8 (6.5-29.0) |
| Atd, Sti, Aag | 15.1 (5.0-25.1) |
| Atp, Sti, Aag | 11.8 (1.3-22.4) |
| Sti, Msb, Aag | 9.7 (2.5-16.8) |
| 2005-2010 | |
| Atp, Atd, Sti | 21.6 (12.9-30.2) |
| Atp, Sti, Aag | 17.4 (7.7-17.0) |
| Atp, Sti, Msb | 11.8 (5.8-17.8) |
| Atd, Sti, Aag | 10.4 (3.9-16.9) |
| 2011-2015 | |
| Atp, Sti, Aag | 21.8 (13.7-29.8) |
| Atp, Atd, Sti | 16.7 (8.7-24.6) |
| Atd, Sti, Aag | 13.9 (7.4-20.4) |
| Atp, Atd, Msb | 9.9 (3.3-16.6) |
Abbreviations: Aag, α-agonists; Atd, antidepressants; Atp, antipsychotics; Msb, mood stabilizers; Sti, stimulants.
Only combinations reported in 10% or more of youths treated with psychotropic polypharmacy were presented.
Discussion
Attention-deficit/hyperactivity disorder is the predominant diagnosis among youths who received psychotropic polypharmacy. The findings suggest an increase in concurrent use of antipsychotics with other psychotropics. Use of mood stabilizers decreased possibly as more youths received antipsychotics for mood disorders. Evidence of the efficacy and safety is needed to guide psychotropic polypharmacy practice. A study limitation is that the definition of psychotropic polypharmacy may have obscured medication switching.
References
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