NADD Bulletin Volume XI Number 2 Article 1

Complete listing

The Mostly “Off Label” Use Of Psychoactive Drugs In Children And Adolescents With Autistic Spectrum Disorders And /Or Intellectual Disability

Howard Demb, M.D; Tammy Fried, LMSW


There have been a variety of reports about the use of psychotropic medications with individuals with mental retardation (intellectual disability), and other developmental disabilities. These have included:  general reviews (Aman, Lam, & Van Bourgondien, 2005; Antochi & Stavrakaki, 2004; Hanft & Hendren, 2004; Madrid, State, & King, 2000) reports of the use of specific medications (Arnold, Aman, Cook, Witwer, Hall, Thompson, & Ramadan, 2006; Pandina, Aman, & Findling, 2006); statewide surveys (Spreat, Conroy, & Fullerton, 2004); reports of the use of psychotropic medications in preschool children (Rappley, 2006); the use of psychotropic medications in children with an autistic spectrum diusorder with co-occurring symptoms of hyperactivity, impulsivity or inattention, (Melmed & Reynolds, 2007); journal (Zito, 2007) and newspaper reports questioning the use of these medications (Harris, 2006); and, the devotion of an entire issue of the American Journal of Mental Retardation to this topic (Rush & Frances, 2000). With the exception of Zito (2007), and Zito, Safer, Valluri, Gardner, Korelitz & Mattison, (2007), these reports have not focused on the “off-label” use of these medications.  “Off-label” (Steels, 2002), refers to the use of these medications with children who are younger than the approved minimum age and/or for a diagnosis for which approval has not yet been granted by the Food and Drug Administration (FDA).

The “off-label” use of psychotropic medications is not uncommon (Zito, Safer, Valluri, Gardner, Korelitz & Mattison, 2007) and can be as high as 12% of preschool children with an Axis I (DSM-IV-TR, APA, 2000) disorder (Luby, Stalets, & Belden, 2007). There is, therefore, a need for short and long term outcome research on the use of psychotropic medication in what is currently an “off-label” fashion, so that indications for an approved use of theses medications can be formulated. This has recently happened with risperidone, a second generation antipsychotic often used “off-label” in the past for treating aggression in persons with autism. Risperidone recently has been approved by the FDA for treating symptoms of irritability, temper tantrums, self-injurious behaviors, and aggression in persons with an autistic disorder. The approval took place after the data from this study was collected, so that the use of risperidone to treat behavior problems in children with an autistic disorder was considered “off-label” in this study.

As a step in the direction of trying to get other medications approved, we present data on the use of psychotropic medications, in what is often an “off-label” fashion, to treat behavioral and/or emotional symptoms in a population of individuals with an autistic spectrum disorder (ASD) and/or an intellectual disability (ID).


This is a chart review study to present a summary of the use of psychotropic medications in an urban, university affiliated diagnostic and treatment center serving children, and adolescents with developmental disabilities. This study is a review of how medications are used at our Center, either singly or in combination, and often in a “off-label” fashion, with children and adolescents, with autistic spectrum disorders and/or with intellectual disability.  We present data on all of the children and adolescents with an ASD and/or ID receiving pharmacotherapy for behavioral or emotional problems. The target symptoms are usually hyperactivity, temper tantrums, impulsiveness, aggression, or sleep disorders. The patients are treated with a wide variety of psychotropic medications. The parents of all the patients in the study agreed to the use of these medications in an “off label” fashion.

The charts of all of the children and adolescents with a diagnoses of an ASD (autistic disorder, Asperger syndrome, or pervasive developmental disorder NOS) and/or an ID who were treated with pharmacotherapy for emotional and/or behavioral disorders were reviewed.  The chart reviews covered an 8-year period, ending in the winter of 2006-2007.  In all, 233 charts were reviewed.  These included all (N=88) children/adolescents with an ASD and all (N=145) children/adolescents with ID treated at the clinic over the past 8 years.  There were 69 children with both an ASD and ID in this population. The clinic treats children and youth ranging in age from approximately 2½ to 21 years.


The following information was obtained from the charts: age, sex, diagnosis, chief complaint, target symptoms, medication(s) used, and, whether or not use was “off-label”.  For the purpose of this study the term “off-label” will mean the use of any anticonvulsant to treat a condition other than a seizure disorder; the use of any antidepressant to treat a condition other than a depression or an anxiety disorder; the use of any stimulant to treat a target symptom (e.g. hyperactivity), which is not associated with a diagnosis of an Attention-Deficit/Hyperactivity Disorder; the use of methylphenidate to treat any child less than 6 years of age; and/or the use of any antipsychotic medication to treat any target symptom of a child or adolescent under the age of 16.  During the study period, the antipsychotic risperidone was used to treat symptoms of aggression, temper tantrums, self-injurious behaviors or quickly changing moods in persons with an ASD in an “off-label” fashion.  As of this moment, such use is no longer “off-label” when used with children and adolescents with an autistic disorder between the ages of 5-16 years. The authors reviewed the charts to decide which medications reported on in the study are used “off-label.”



In all, 9 different classes of medication have been used (Table 1).  The 233 children received a total of 300 medications or medication combinations.  Sixty-six children were treated with more than 1 class of drugs.  In 224 cases (75%) the medications were “off-label,” while in 76 cases (25%)  the medications were used in an approved fashion (Table 1). If one were to consider the use of risperidone to treat symptoms of aggression, temper tantrums, self injurious behavior or mood instability in children and adolescents with an autistic spectrum disorder as an approved indication (as is currently the case), then the number of “off-label” uses drops to 174 (58%) and the number of approved uses rises to 126 (42%).

During the study period, all of the uses of antipsychotics with 111 children were “off-label.”  All but 2 of the children were treated with atypical antipsychotics (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone).  The most frequently used antipsychotic was risperidone, which accounted for 58% of the cases in which an antipsychotic was used. Antipsychotics were used with 70% of the children with autism (AD) and (ID), in 48% of children with AD, in 38% of the children with ID, and in 28%of the children with Asperger’s disorder (AS) or pervasive developmental disorder NOS (PDD NOS).  Stimulants or atomoxitine were used in an approved fashion in 62% of the children with ID.  This was the only approved use of stimulants.  Stimulants were used in an “off-label” fashion in 60% of the children with AS/PDDNOS, in 37 % of the children with an AD and in 30% of the children with AD+ID (Table 2). Alpha-blockers, (clonidine, guanfacine), approved to treat hypertension, and the antidepressant trazodone, were used to treat sleep disorders in an “off-label” fashion in 40 children. Clonidine was the most frequently used medication for this indication and was used in 14% of this population.

For children with ID, antipsychotics were combined with up to 3 other classes of medication (stimulants, anticonvulsants, alpha blockers).  Seventy-four children (32%) were treated with more than 1 class of medication.  A child with AD+ID who was treated with an antipsychotic could have one or more of 4 different classes of medication added to the treatment regimen.  A child with AD+ID who was treated with an alpha blocker could have one or more of 5 different classes of medications in his/her treatment regimen.  The most frequent combination for a child with an ID was an antipsychotic (risperidone) and an alpha blocker (clonidine). 


Medications are often used to treat symptoms of aggression, self abuse, hyperactivity, and sleep disorders in children and adolescents with an ASD and/or ID. Until recently there were no medications which were approved to treat individuals with an ASD and/or ID who did not have a diagnosable comorbid emotional and/or behavior disorder.  This study involved children and adolescents who were treated before the atypical antipsychotic resperidone was approved for the treatment of aggression, mood instability and self-abuse in children and adolescents with an AD.  The use of medications to treat children and adolescents at our Center involved the mostly “off-label” use of atypical antipsychotics, and stimulants, which together were used with 74% of the children, to treat hyperactivity, aggression, self-injury, and temper tantrums.  The next most commonly used class of medication was alpha blockers which were used in treating sleep onset disorders in 14% of the children.  This distribution was similar to that reported by Bildt, Mulden, Sheens, Minderoa, & Tobi, (2006) and Staller (2007) and by Langworthy-Lam, Aman, & Van Bourgondien, (2002) in their compilation of data from the state of North Carolina, except for the more limited use of antidepressants in our setting.  Since the “off-label” use of psychoactive medications are common when treating behavior and emotional problems in children and adolescents with ID and/or ASD’s, there is clearly a need for well controlled randomized studies with these medications for these indications in this population. The goal in the “off-label” use of these medications is to improve social and educational functioning and to try to avoid school suspensions or psychiatric hospitalizations. Future research should, therefore, be designed to determine whether the “off-label” use of these medications are safe, effective, and tolerable in community based populations. If the results are promising, as in the Research Units in Pediatric Psychopharmacology  (RUPP) studies on methylphenidate (Ritalin and others, 2005) or on risperidone (2002), the FDA might be able to approve the use of these medications, as it has done with risperidone.




Classes of Medications Used and Number of Cases in Each Class




CLASS:“Off Label”Approved               TOTAL 


Antipsychotics a111  0111

Antipsychotics  b 6150111

Stimulants 5742  99

Alpha blockers 39  0  39

Anticonvulsants   922  31

Antidepressants   410  14

(with trazodone)

Anxiolytics   1  1    2

Beta blockers   2  0    2

Opiod antagonists 1  0                               1


Total (a)22476300

Total (b)174        126300



a  With the use of risperidone during the study period

b  Risperidone considered approved in some cases







Approved and “Off Label” uses of the Three Most Frequently Used Classes of Medication-Percentage of Children






   Approved 0 0 0 0




   Approved 0 062  0

   “Off-label”3760 030


Alpha Blockers

   Approved 0  0  0 0

   “Off-label”13  7  925



“Off-Label” use – for all medications

AD > ID (p = 0.001)

AD + ID > AD (p = 0.05)




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