Concomitant Psychotropic Medication for Youths

Safer, Daniel J.; Zito, Julie Magno; dosReis, Susan

doi:10.1176/appi.ajp.160.3.438

Cited by 140 publications

(116 citation statements)

References 124 publications

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“…50 There also is little systematic evidence for the use of psychotropic medications in combination. 51 These issues speak to the importance of scientific studies' keeping pace with practice. Although traditional randomized trials may not be feasible or ethical, careful naturalistic studies of the risks, benefits, and costs of psychotropic medication use in children with ASDs are warranted.…”

Section: Discussionmentioning

confidence: 99%

Psychotropic Medication Use Among Medicaid-Enrolled Children With Autism Spectrum Disorders

et al. 2008

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OBJECTIVE-The objective of this study was to provide national estimates of psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders and to examine child and health system characteristics associated with psychotropic medication use.METHODS-This cross-sectional study used Medicaid claims for calendar year 2001 from all 50 states and Washington, DC, to examine 60 641 children with an autism spectrum disorder diagnosis. Logistic regression with random effects was used to examine the child, county, and state factors associated with psychotropic medication use.RESULTS-Of the sample, 56% used at least 1 psychotropic medication, 20% of whom were prescribed ≥3 medications concurrently. Use was common even in children aged 0 to 2 years (18%) and 3 to 5 years (32%). Neuroleptic drugs were the most common psychotropic class (31%), followed by antidepressants (25%) and stimulants (22%). In adjusted analyses, male, older, and white children; those who were in foster care or in the Medicaid disability category; those who received additional psychiatric diagnoses; and those who used more autism spectrum disorder services were more likely to have used psychotropic drugs. Children who had a diagnosis of autistic disorder or who lived in counties with a lower percentage of white residents or greater urban density were less likely to use such medications.CONCLUSIONS-Psychotropic medication use is common among even very young children with autism spectrum disorders. Factors unrelated to clinical presentation seem highly associated with prescribing practices. Given the limited evidence base, there is an urgent need to assess the risks, There is ongoing debate regarding the role of psychotropic agents in ASD management. 2,3 Although no medications are known to address the core symptoms of ASDs, they often are prescribed as adjunctive therapy to address symptoms such as aggression, self-injurious behaviors, stereotypies, and hyperactivity. [4][5][6] Many medications have been tested with varying levels of scientific rigor, 7 but only risperidone, an atypical neuroleptic that reduces aggression and irritability, has received Food and Drug Administration approval for the treatment of these symptoms in individuals with ASDs. 8Medication use is common among children with ASDs and seems to be increasing. A 1995 survey found that 30% of children with ASDs were using some psychotropic medication 9 ; follow-up studies 6 years later found 46% using them. 10,11 Neuroleptic agents were most common in 2 of 3 studies, 9,11 with antidepressants the most common in the third. 10 In 2001, 21% were using >1 drug, compared with 8% in 1995. A 2005 international Internet survey found that 52% of parents reported that their children were using psychotropic drugs. 12 These studies provided important information regarding psychotropic medication use in children with ASDs, but all relied on parent report, the validity of which is unknown. With 1 exception, 12 they sampled relatively small geographic areas, and all exc...

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Section: Discussionmentioning

confidence: 99%

Psychotropic Medication Use Among Medicaid-Enrolled Children With Autism Spectrum Disorders

et al. 2008

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“…These situations often lead to the use of various drugs in combination. A growing trend towards combination pharmacotherapy in all of child, adolescent and adult psychiatric practice has been well documented over the past decade (Connor et al, 1997;Safer et al, 2003;Wilens et al, 1995). Thus, potential P-glycoprotein mediated drug interactions occurring with combined pharmacotherapy on an acute or chronic basis could have therapeutic implications for patients receiving medications for ADHD (Markowitz and Patrick, 2001).…”

Section: Discussionmentioning

confidence: 99%

Interactions of attention-deficit/hyperactivity disorder therapeutic agents with the efflux transporter P-glycoprotein

Zhu

Wang

Donovan

et al. 2008

European Journal of Pharmacology

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The objective of this study was to assess the potential interactions of the drug transporter Pglycoprotein with attention-deficit/hyperactivity disorder (ADHD) therapeutic agents atomoxetine -and the individual isomers of methylphenidate, amphetamine, and modafinil utilizing established in vitro assay. An initial ATPase assay indicated that both d-and l-methylphenidate have weak affinity for P-glycoprotein. The intracellular accumulation of P-glycoprotein substrates doxorubicin and rhodamine123 in the P-glycoprotein overexpressing cell line LLC-PK1/MDR1 was determined to evaluate potential inhibitory effects on P-glycoprotein. The results demonstrated that all compounds, except both modafinil isomers, significantly increased doxorubicin and rhodamine123 accumulation in LLC-PK1/MDR1 cells at higher concentrations. To investigate the P-glycoprotein substrate properties, the intracellular concentrations of the tested compounds in LLC-PK1/MDR1 and P-glycoprotein negative LLC-PK1 cells were measured in the presence and absence of the Pglycoprotein inhibitor PSC833. The results indicate that the accumulation of d-methylphenidate in LLC-PK1 cells was 32.0% higher than in LLC-PK1/MDR1 cells. Additionally, coadministration of PSC833 leads to 52.9% and 45.6% increases in d-modafinil and l-modafinil accumulation, respectively, in LLC-PK1/MDR1 cells. Further studies demonstrated that l-modafinil transport across LLC-PK1/MDR1 cell monolayers in the basolateral-to-apical (B-A) direction was significantly higher than in the apical-to-basolateral (A-B) direction. PSC833 treatment significantly decreased the transport of l-modafinil in B-A direction. In conclusion, our results suggest that all tested agents with the exception of modafinil isomers are relatively weak P-glycoprotein inhibitors. Furthermore, P-glycoprotein may play a minor role in the transport of d-methylphenidate, dmodafinil, and l-modafinil.

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“…The practice of using medications in combination is increasingly widespread. Safer et al (2003) recently reviewed clinical research and practice literature from 1996-2002 to assess frequency of concomitant psychotropics for youths. They reported that during 1997-1998 almost 25% of the representative physician office visits for youths in which a stimulant prescription was written were also associated with use of concomitant psychotropic medication.…”

Section: Risks Of Combining Stimulants With Atxmentioning

confidence: 99%

Atomoxetine and Stimulants in Combination for Treatment of Attention Deficit Hyperactivity Disorder: Four Case Reports

Brown

2004

Journal of Child and Adolescent Psychopharmacology

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Atomoxetine and stimulants have both been demonstrated effective as single agents for treatment of attention deficit hyperactivity disorder in children, adolescents, and adults. However, attention deficit hyperactivity disorder symptoms in some patients do not respond adequately to single-agent treatment with these medications, each of which is presumed to impact dopaminergic and noradrenergic networks by alternative mechanisms in different ratios. Four cases are presented to illustrate how atomoxetine and stimulants can be utilized effectively in combination to extend duration of symptom relief without intolerable side effects or to alleviate a wider range of impairing symptoms than either agent alone. This combined pharmacotherapy appears effective for some patients who do not respond adequately to monotherapy, but because there is virtually no research to establish safety and effectiveness of such strategies, careful monitoring is needed.

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Concomitant Psychotropic Medication for Youths

Abstract: Substantive systematic evidence is needed to clarify this increasingly common, inadequately researched child psychopharmacologic practice.

Cited by 140 publications

References 124 publications

Psychotropic Medication Use Among Medicaid-Enrolled Children With Autism Spectrum Disorders

Psychotropic Medication Use Among Medicaid-Enrolled Children With Autism Spectrum Disorders

Interactions of attention-deficit/hyperactivity disorder therapeutic agents with the efflux transporter P-glycoprotein

Atomoxetine and Stimulants in Combination for Treatment of Attention Deficit Hyperactivity Disorder: Four Case Reports

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