Study Reports Parents Observe Multiple Psychotropic Medications Increase Side Effects and Their Severity

parent and child 2

In the first study to explore the real world use of psychotropic medications focusing on the connection between the number of psychiatric medications used by children and the number and severity of side effects experienced, parents report that adverse effects are more common and more severe as the number of psychotropic medications administered to the child increase.  The study was published in the Journal of Child & Adolescent Psychopharmacology.[1]   The findings provide support for professional guidelines and the red flags established by some states requiring special review [second opinions] or prior authorization whenever multiple psychotropic medications are prescribed for a child in foster care.[2]  It also suggests that setting the threshold for such reviews at four or more medications should be adjusted downwards.

Researchers at the University of Washington surveyed parents of children ages 3-17 years old taking one or more psychiatric medications.  Information was collected using the Child Psychopharmacological Experiences Survey (CPES) designed by the authors.  The survey form included a standardized symptom review rather than soliciting side effects through open-ended queries.  It included 10 body systems and included items for weight gain, weight loss, gastro-intestinal upset, headaches, insomnia, irritability, and tremors among others.  Parents also were asked to identify the severity of the side effect – mild, moderate, or severe.

An introductory letter was sent to all parents with a child ages 3-17 who filled a prescription for at least one psychotropic medication in a retail pharmacy system.  Surveys could be completed either on-line or on a written form returned by U.S. mail.  Over 1300 parents from 30 states returned the questionnaires. More than two thirds of the children (67%) had taken medication for more than a year.  Almost four in ten of the children (39%) received two or more medications.

The authors reported these findings from the parent survey

  • On average, the number of side effects did not vary significantly with age, gender, or race.
  • The number of side effects increased the longer the child was on the medication
  • The number of side effects increased with the number of medications being used. In comparison with children taking one medication, those taking two drugs reported 17% higher risk of side effects while those taking three o more medications reported a 38% increase in side effects.
  • The most common and severe side effect profile shifted for children depending upon the number of medications.  Common side effects reported for children taking one medication included decreased appetite, insomnia, and irritability while children taking three or more medications suffered from irritability, sleepiness/fatigue, and increase appetite.

Concomitant prescribing of psychotropic medication among children and adolescents is well-documented; large-scale studies of the practice go back more than a decade.[3]  It occurs across drug classes[4] as well as within the same class of drugs.[5]  Despite the absence of evidence of the safety, efficacy or effectiveness for the long-term use of these drug combinations, [6] the practice persists. Children in foster care are more likely than others to be administered multiple psychotropic medications.[7]  This most recent study provides further support for subjecting polypharmacy for children to close scrutiny.

[1] Robert Hilt MD, Monica Chaudhari, et al, Side Effects form the Use of One or More Psychiatric Medications in a Population-based Sample of Children and Adolescents, 24 J. Child & Adolesc. Psychopharmacology 83 (2014).

[2] E.g., Los Angeles County Dep’t of Mental Health, 03.9 Parameters for Juvenile Court Mental Health Services’ Review of Psychotropic Medication Application Forms for Youth in State Custody (May 1, 2013); Rhode Island Dep’t of Children, Youth, and Families, Staff Protocol 1300.0052 (February 10, 2014);  Texas Parameters… AACAP 2009 Parameters… Choosing Wisely…

[3] Daniel J. Safer, Julie Magno Zito, Susan dosReis, Concomitant Pscyhotropic Medication for Youths, 160 J. Amer. Psychiatric Assoc. 438 (2003)(citing studies by Olffson et al, and Betts, et al in 2002); Anna Kreider, M. Matone, et al, Growth in the Concurrent Use of Antipsychotics With Other Psychotropic Medications in Medicaid-Enrolled Children, J. Amer. Acad of Child & Adolesc, Psychiatry (in press);

[4] Keith A. Betts Ph.D, Vanja Sikirica Phamr D., et al, Period Prevalence of Concomitant Psychotropic Medication Usage Among Children and Adolescents with Attention-Deficit/Hyperactivity Disorder During 2009, 24 J. Child & Adolesc. Psychopharmacology 260 (2014).

[5] Mehmet Burcu MS, Julie Magno Zito, et al, Atypical Antipsychotic Use Among Medicaid-Insured Children and Adolescents: Duration, Safety, and Monitoring Implications, 24 J. Child & Adolesc. Psychopharmacology 112 (2014); RJ Constantine, T Boaz, et al, Antipsychotic Polypharmacy in the Treatment of Children and Adolescents in the Fee for Service Component of a Large State Medicaid Program,  Clinical Therapeutics 949 (2010)

[6] The AACAP Parameters (2009) have this to say about concomitant use:

In contrast to what is known about treatment with a single psychotropic medication, there is a smaller evidence base supporting the efficacy of medication combinations.40 Psychotropic medication combinations are commonly used to address complex comorbid presentations,41–43 to enhance outcome for treatment-refractory or partially responsive patients,43,44 to manage side effects of an effective agent (e.g., anticholinergic medication for extrapyramidal symptoms), or to address symptoms hypothesized to be associated with multiple underlying neurotransmitter abnormalities (e.g., dopamine agonists for hyperactivity and serotonin agonists for anxiety45). Although the design of studies of a single medication is relatively straightforward (e.g., randomized controlled trials), studies of medication combinations, combining medication and psychotherapy,18,32,46 and studies to address the sequence of treatment for complex presentations require more complex study designs47 and are more costly to implement (e.g., Sequenced Treatment Alternative to Relieve Depression). The cost and complexity of these studies may partially explain the lack of such studies in children and adolescents.

See also, Principle 12

[7] Burcu, et al supra, at 440; Jule Magno Zito, Danile J. Safer, et al, Psychotropic Medication Patterns Among Youth in Foster Care, 121 Pediatrics e157 (2008); Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado, Psychotropic Medication Use in Colorado Medicaid Children and Adolescents; A Focus on Foster Care Children

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