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More importantly, many pharmacologic treatments are being prescribed off-label to autistic children with little research to support such use and, when studied, most of the research includes only a small number of subjects. For example, in a 2001 survey in North Carolina (Langworthy-Lam, Aman, & Van Bourgondien, 2002), 26% of respondents reported using buspirone despite a lack of supportive placebo-controlled studies. In some facilities, guanfacine is considered a first-line drug treatment for Attention Deficit/Hyperactivity Disorder (ADHD) symptoms in autistic children (McDougle, 2004), even though only one placebo-controlled study exists. In addition, drugs such as clomipramine have failed to show efficacy in the autistic population yet have been prescribed to autistic children (Aman, Van Bourgondien, Wolford, & Sarphare, 1995). With the exception of risperidone, the FDA has not approved any pharmacologic drug for the treatment of autism in children. However, caretakers may seek help in identifying pharmacotherapy as an adjunct to current behavioral and educational management even if it is prescribed off-label. Unfortunately, without knowing pharmacotherapy options and possible behavioral effects, the search for appropriate pharmacotherapy may prove long, arduous, and frustrating for the practitioner, caretaker, and patient. The purpose of this article is to examine the evidence for specific pharmacological treatments for the core deficits and associated symptoms of autism in children. With the exception of risperidone, the FDA has not approved any pharmacologic drug for the treatment of autism in children. Methods Pub-Med and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched for peer-reviewed, English-language studies using the key terms autism, pervasive developmental disorder, pharmacotherapy, antipsychotics, antidepressants, stimulants, anticonvulsants, opiate antagonists, alpha-2-noradrenergic agonists, N-methyl-D-aspirate (NMDA) receptor antagonists, acetylcholinesterase inhibitors, and specific drug names. Studies were selected with emphasis given to meta-analyses, and prospective experimental and quasi-experimental studies in autistic children ages 5 to 18 years conducted in the U.S. Searches returned 12 randomized clinical trials and nine other prospective studies. Study authors, research design, sample size, dosing schedules, and adverse effects are summarized in Table 2.
ResultsResults are presented by class of compounds, according to the strength of overall evidence for the efficacy of that class. The research reviewed shows moderate success in treating the associated behaviors of autism and minimal success in treating core deficits. Criteria for judging efficacy of therapy varied according to study design, sample size, and measurement instruments; the investigators' interpretations were accepted for this review. Assessment instruments used to quantify behavioral responses to treatment included the Aberrant Behavior Checklist-Community Version (ABC-CV), Clinical Global Impressions Scale (CGI), Vineland Adaptive Behavior Scale (VABS), Ritvo-Freeman Real Life Rating Scale, Self Injurious Behavior Questionnaire (SIBQ), Child Autism Rating Scale (CARS), Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Screen for Child Anxiety Related Emotional Disorders (SCARED), Swanson, Nolan and Pelham Questionnaire-IV (SNAP-IV) for the DSM-IV criteria for ADHD, and the Child Psychiatric Rating Scale. Treatment effect was most often measured by assessing behavioral changes using the ABC and the CGI subscales of illness severity (CGI-S) and global improvement (CGI-I). Unless otherwise specified, “responder” is defined as an improvement on the CGI of very much improved or much improved. Antipsychotic AgentsTypical and atypical antipsychotic agents have shown some efficacy in the treatment of autism. Conventional neuroleptic agents such as haloperidol have been used to treat the more aggressive and violent behaviors associated with autism, but their neurologic adverse effects are often unacceptable. Some success in treating the more disruptive behaviors of autism is attributed to haloperidol, but it has been used sparingly because of the high risks of extra pyramidal symptoms (EPS), tardive dyskinesia, and withdrawal dyskinesia (Campbell et al., 1997, Malone et al., 2002, Research Units on Pediatric Psychopharmacology Autism Network, 2002. Long term-use of haloperidol increases the risk of withdrawal dyskinesia and, without medication holidays, may result in irreversible tardive dyskinesia (Campbell et al.). As a result, only one study comparing haloperidol with olanzapine has been conducted during the past 10 years, and the results support the findings of earlier studies (Malone, Cater, Sheikh, Choudhury & Delaney, 2001). Several atypical antipsychotic agents may be helpful in the treatment of disruptive and maladaptive behaviors associated with autism. Currently, the atypical antipsychotic agents risperidone and olanzapine have demonstrated more favorable results than have other similar atypical antipsychotics. RisperidoneRisperidone is the most widely researched drug for behavior modification in children with autism. In October 2006, the FDA approved risperidone for the treatment of irritable, aggressive, and self-injurious behaviors in children with autism, and currently it is the only drug approved for the treatment of autism (FDA, 2006). Risperidone is a dopamine and serotonin receptor antagonist that has a high affinity for serotonin receptors (Taketomo, Hodding, & Kraus, 2003). Several studies of risperidone in autistic children use similar doses and schedules and show similar results (Table 2). All of the studies find risperidone to be safe and effective for a variety of symptoms associated with autism (See West & Waldrop, 2006, for a review). Overall improvement from baseline on the CGI-I scale (P < 00.1, Perry et al., 1997, Findling et al., 1997) and compared with placebo (P < .001, RUPPAN, 2002) and with the CARS (P < .005, Findling, Maxwell, & Wiznitzer, 1997). Responder rates of 66% to 82.5% (CGI) also were noted (McDougle et al., 1997, Research Units on Pediatric Psychopharmacology Autism Network, 2005b). Significant decreases from baseline were found for compulsive behavior (CY-BOCS) (P < .0001, McDougle et al., 1997; P = .005, McDougle et al., 2005). Using the irritability and stereotypy (P = .02) subscale of the VABS, significant improvement was noted from baseline (RUPPAN, 2005b). Irritability also was improved compared with placebo (P < .001) (RUPPAN, 2002). The Ritvo Freeman Real Life Rating Scale showed overall improvement from baseline (P < .009, McDougle et al., 1997; P < .001, McDougle et al., 2005). Subscales on affectual reactions (P < .008, P < .008), sensory response (P < .005, P = .004) (McDougle et al., 1997, McDougle et al., 2005, respectively) and sensory motor behaviors (P = .002, McDougle et al., 2005) improved as well. Improvement from baseline also was significant in the maladaptive behavior component of the VABS (P < .001) (McDougle et al., 2005) and in the aggression component (SIBQ) (P < .0001, McDougle et al., 1997). In addition, 68% of the responders maintained a positive response during a 4-month drug maintenance phase (Research Units on Pediatric Psychopharmacology Autism Network, 2005a, McDougle et al., 2005); however, no further improvements were seen in any of the measurements. Adverse effects included weight gain in 67% to 83% of subjects, sedation in 33% to 66% of subjects, and increased serum prolactin levels by as much as 57% (Table 2). OlanzapineLike risperidone, olanzapine is a dopamine and serotonin receptor antagonist with high affinity binding for dopamine receptors as well as muscarinic, histamine, and adrenergic receptors (Eli Lilly, 2006). Two small studies (Table 2) demonstrated significant improvement over time (P < .05) for all items in the autism factor of the Child Psychiatric Rating Scale except underproductive speech (Malone et al., 2001) and a 50% to 83% responder rate (GCI) (Hollander et al., 2006, Malone et al., 2001). However, no statistically significant changes in GCI were observed. No reports of abnormal movements, EPS, or dyskinesias are described, but weight gain and sedation were again notable adverse effects (Malone et al., 2001, Hollander et al., 2006) (Table 3).
QuetiapineQuetiapine is a dopamine and serotonin receptor antagonist as well as a histamine and adrenergic receptor antagonist (Lacy, Armstrong, Goldman, & Lance, 2006). Because similar antipsychotic agents have demonstrated efficacy in the treatment of disruptive behaviors of autism, quetiapine was anticipated to yield similar results. However, studies (Table 2) showed no significant improvements, and adverse effects caused many subjects to drop out of the studies (Martin et al., 1999, Findling et al., 2004). Although no medication-related EPS were reported by either study, researchers concluded that quetiapine is not effective or well tolerated for the treatment of autism symptoms. AntidepressantsThe similarity of autism symptoms to serotonin-related disorders such as obsessive compulsive disorder has led researchers to investigate the efficacy of serotonin reuptake inhibitors and selective serotonin reuptake inhibitors (SSRIs) in the treatment of autism. SSRIs inhibit serotonin reuptake (Posey, Erickson, Stigler, & McDougle, 2006) but have little effect on the reuptake of other neurotransmitters such as dopamine and noradrenalin, which limits the adverse affects of SSRIs. Unfortunately, there are few prospective or replicated placebo-controlled, double-blind studies supporting their use in the pediatric autistic population. FluvoxamineAn open-label study of fluvoxamine in autistic children ages 7 to 18 years showed no significant improvement in global functioning (GCI), repetitive behaviors (CY-BOCS) or anxiety symptoms (SCARED) from baseline. Responder rate (as measured by either a 25% decrease in either CY-BOCS, SCARED, or improvement on the GCI) was 100% for female subjects (four of four) compared with 29 for male subjects (four of 14) (Table 2). Unfortunately, adverse effects of agitation, behavior activation, and insomnia in 50% of the subjects were noted (Martin, Koenig, Anderson, & Scahill, 2003) (Table 2). FluoxetineIn the only placebo-controlled crossover trial, fluoxetine was superior to placebo (P = .004, effect size 0.76) in reducing repetitive behaviors (CY-BOCS). Although there was a 56% improvement (GCI), it was not statistically significant compared with placebo (Hollander, Phillips, et al., 2005) (Table 2). No significant adverse effects, including suicidal ideation, were noted when compared with placebo. The few adverse effects noted, even though not significant, were sedation, agitation, and anorexia. EscitalopramUse of escitalopram showed significant overall improvement compared with placebo (CGI, P < .001). Significant improvement from baseline also was demonstrated by the ABC in irritability, lethargy, stereotypy, hyperactivity, and inappropriate speech (P < .001). Unfortunately, escitalopram showed adverse effects of irritability and hyperactivity with increasing dose. A variable dose range for tolerability also was reported (Table 2, Table 3) (Owley et al., 2005). SSRIs are helpful in treating the core deficits of communication and socialization as well as repetitive, irritable, and anxiety symptoms of autism. SSRIs are helpful in treating the core deficits of communication and socialization as well as repetitive, irritable, and anxiety symptoms of autism. Autistic children show moderate responses to the SSRIs fluvoxamine and fluoxetine, while escitalopram decreases hyperactivity, irritability, anxiety, and repetitive behaviors in autistic children. Of particular interest is fluvoxamine, because female autistic subjects show a selective response to this drug. Although only one study asked about suicidal ideation (Hollander, Phillips, et al., 2005), the sample was small and the probability still exists and should be monitored for all children taking SSRIs. Unfortunately, many drugs in the antidepressant class are often plagued by intolerable adverse effects. Medications Used for Attention Deficit Hyperactivity Disorder SymptomsSymptoms of ADHD are not unusual in the course of autism and frequently are targeted by pharmacologic interventions (Handen, Johnson, & Lubetsky, 2000). ADHD symptoms are the most common associated symptoms of autism; more than 50% of autistic children have moderate to severe difficulties with distractibility, concentration, finishing tasks, hyperactivity, excitability, fidgetiness, and decreased attention span (Lecavalier, 2006). Unfortunately, stimulants are not as effective in the autistic population and have increased adverse effects when compared with their effects on typically developing peers. For example, methylphenidate has a success rate of 70% (Greenhill et al., 2001) to 90% (Elia, Borcherding, Rapoport, & Keysor, 1991) in controlling ADHD symptoms in typically developing children, with adverse effects as low as 1.4% (Greenhill et al., 2001). MethylphenidateMethylphenidate stimulates the brain stem and cerebral cortex by blocking the reuptake of norepinephrine and dopamine to increase the availability of these neurotransmitters (Taketomo, Hodding, & Kraus, 2006). Methylphenidate demonstrated a significant effect on the hyperactivity subscale of the ABC (P < .009 teacher; P < .001 parent) and a significant improvement over placebo in the stereotypy (P = .05) and inappropriate speech (P = .02) subscales (RUPPAN, 2005b). In a study by Handen et al. (2000), almost 62% of children demonstrated a response as defined by a 50% decrease in the Teacher Connors Hyperactivity Index (P < .0086). The hyperactivity (P < .003), stereotypy (P < .008) and inappropriate speech (P < .001) subscales of the ABC were also significantly better than placebo. However, a different global assessment tool (CARS) found no change in global autism symptoms or improvement in core deficit behaviors (Table 2). Adverse effects of irritability, lethargy, sadness, dullness, and social withdrawal increase with higher methylphenidate doses (Handen et al., 2000, Research Units on Pediatric Psychopharmacology Autism Network, 2005b). Because a high rate of adverse effects was also noted in the placebo group (Handen et al.), it is difficult to identify and attribute significant adverse effects to methylphenidate (Table 2). AtomoxetineAtomoxetine is a selective norepinephrine reuptake inhibitor with a 43% response rate, defined as 25% improvement on the ABC-Hyperactivity Subscale and GCI (Arnold et al., 2006) and a 75% response rate (CGI) in children with autism (Posey, Wiegand, et al., 2006). In addition, the GCI showed significant improvement from baseline (P = .0007) (Posey, Wiegand, et al.). Significant improvements also were demonstrated from baseline in inattention (SNAP-IV subscale, parent P < 0.0001, teacher P = .005), hyperactivity/impulsivity (SNAP-IV subscale, parent and teacher P < .0001; ABC, teacher P = .004, parent P < .0001) and oppositional behavior (SNAP-IV subscale, teacher P = .002), social withdrawal (ABC subscale, parent P = .003), stereotypy (ABC subscale, parent P = .0001), and maladaptive behaviors (part 1, P = .0003, part 2, P = .003) (Posey, Wiegand et al., 2006). Arnold et al. (2006) also demonstrated significant improvements compared with placebo in hyperactivity/impulsivity (ABC subscale P = .04, DSM-IV symptoms P = .005) (Table 2). Adverse effects were minimal with the exception of a 4% increase in heart rate in 25% of subjects and a significant decrease in weight (P = .006) (Arnold et al, 2006). Methylphenidate and atomoxetine demonstrate notable decreases in hyperactivity, impulsivity, stereotypy, and inappropriate speech in autistic children. Although the response rate with methylphenidate is lower in autistic children than in typically developing children, methylphenidate is somewhat efficacious in treating the hyperactivity cluster of autism. Unlike some of the other pharmacotherapeutics reviewed, methylphenidate does not exhibit greater efficacy in higher-functioning autistic children (Handen et al., 2000, Research Units on Pediatric Psychopharmacology Autism Network, 2005b). Anticonvulsant AgentsAnticonvulsant agents typically treat seizure disorders but also are used to treat psychiatric disorders with compulsive, impulsive, mood lability, irritability, and aggressive features and to increase the efficacy of SSRIs (Hellings et al., 2005, Hollander et al., 2005). Although the mechanism of action for anticonvulsant agents in autism is not clear, they may affect neurologic pathways already suspected in the pathophysiology of autism. Divalproex sodiumIn the only double-blind trial of divalproex, scores on the CY-BOCS were significantly improved from baseline (P = .05, effect size 1.53). Time spent engaging in compulsive, repetitive behaviors was significantly correlated with total improvement (r = .762, P = 0.002) (Hollander, Soorya et al., 2005) (Table 2). Unlike many other medications, adverse effects reported in the study were minimal. LevetiracetamThe only study using levetiracetam in autistic children finds no significant improvement in core deficits or associated symptoms of autism from baseline or compared with placebo (CGI, ABC) (Table 2). Fewer than 20% of subjects experienced adverse effects, with aggression being the most common (Wasserman et al., 2006). Although divalproex shows some hope for treatment of compulsions and repetitive behavior, placebo, double-blind research is needed. Similarly, few studies address the use of levetiracetam in the treatment of autism, but both of these anticonvulsant agents may have possibilities for autism therapy. Alpha-2 Adrenergic AgonistsAlpha-2 adrenergic agonists traditionally are used for hypertension. However, clonidine and guanfacine often are prescribed to treat inattention, hyperactivity, impulsivity, and aggression associated with autism (Langworthy-Lam et al., 2002). No placebo-controlled studies using clonidine have been conducted, and only one study has been conducted using guanfacine in autistic children. GuanfacineIn the only prospective study of guanfacine in autistic children, guanfacine demonstrated a 48% responder rate (CGI). A significant improvement from baseline also was shown in the ABC subscales of hyperactivity (parent P < .0001, teacher P < .01), irritability (parent P = .01), social withdrawal (parent P < .01) and stereotype (parent P < .01) and SNAP-IV scores (parent P < .0001, teacher P = .01) (Table 2). The study noted minimal effects on blood pressure and heart rate, but irritability, sedation, and sleep disturbances required manipulation of dose or scheduling (Scahill et al., 2006) (Table 2). N-methyl-D-aspirate Receptor AntagonistsAmantadineGlutamate, a neurotransmitter linked to the pathophysiology of autism, is an excitatory amino acid that can cause continual activation of the NMDA receptors (Owley et al., 2006). Amantadine, an antiviral and antiparkinson NMDA receptor antagonist, showed significant improvement from baseline in the hyperactivity (P = .046) and inappropriate speech (P = .008) subscales of the ABC (King et al., 2001). The responder rate of 47% (defined as a 25% improvement in ABC subscales of irritability and/or hyperactivity) was not significantly different from the placebo responder rate of 37%. Adverse effects of amantadine include insomnia and somnolence. Unfortunately, with 74% of the amantadine group reporting adverse effects compared with 70% of the placebo group and a high responder rate from the placebo group, the utility of this study is somewhat limited. DiscussionEven though these studies have small numbers of participants and there is no study that has lasted longer than 8 months, the research reviewed shows moderate success in treating the associated behaviors of autism and minimal success in treating core deficits. With small numbers of participants there is always the risk of a Type II error; there really may be significant differences in treatment efficacy compared with baseline or placebo that are not shown because the study is underpowered. Table 3 identifies possible pharmacologic treatments for target symptoms as a guide for health care providers. Atypical antipsychotic agents are helpful in the treatment of disruptive, aggressive, and maladaptive behaviors associated with autism as well as ADHD symptoms. SSRIs are helpful in treating the core deficits of communication and socialization as well as repetitive, irritable, and anxiety symptoms of autism. Stimulants are helpful in decreasing ADHD symptoms as well as the core deficits of communication and restricted behaviors. Repetitive behavior and compulsions as well as mood lability, irritability, and aggression may be decreased with anticonvulsant agents, while hyperactivity and inappropriate speech may be helped with the NMDA receptor antagonist amantadine. Although no one drug successfully eliminates all of the core deficits or associated symptoms, each drug class has modest ability to decrease the severity of some autism symptoms. More research in all drug classes is absolutely needed to support and validate their use in the pediatric autistic population. The current state of pharmacological research for the treatment of autism has several implications. First, many questions remain unanswered. For example, why do certain drugs improve behaviors and functioning for part of the autistic population and not for others? Why do autistic children with the same target symptoms respond differently to similar drug therapies? Some autistic children respond to 5-HT serotonin antagonists, while others respond best to the inhibition or blocking of dopamine or norepinephrine reuptake. The conceptualization of autism as a spectrum of related disorders may help explain why a “cure” for autism is so elusive. Continued research on the neurophysiology associated with functional behaviors is needed. Specific constellations of presenting symptoms may define a physiologic etiology and lead to pharmacotherapy better tailored for the individual child. Second, because the etiology of autism is not known, choosing medications to treat symptoms must be done cautiously and judiciously. Random prescribing of medications because they work well in normally developing children is haphazard and not in the best interest of the patient or the family. Providers and caretakers must openly discuss target symptoms and how to best manage these symptoms with educational and behavioral therapies while using pharmacotherapy as a way to increase the effectiveness of these therapies. More research is needed not only to explore the new drug choices available but also to explore the efficacy of drug combinations and long-term use. Third, this review reveals a wide range of dosing with varying adverse effects (Table 2) often not correlated with dose, which can make prescribing a challenge for any provider. In general, autistic children have increased sensitivity and intensity of adverse effects to minimal doses of medication when compared with normally developing peers. As a result, the majority of studies began with low doses and titrated upward based on response and tolerance. In the clinical situation, especially when adverse effects are concerning, this cautious approach to advancing treatment would be most prudent. In addition, many of the drugs used are not approved for use in children; pharmacologic management must be cautious for patient safety. Also, many of these drugs are not available in child-friendly formulations. If a child refuses to take a medication because it is only available in table form or tastes bad, then it definitely will not be effective. Compounding pharmacists can make any medication more palatable and easy to take. The International Association of Compounding Pharmacists Web site has a locator service for finding a nearby compounding pharmacist (www.iacprx.org). Research is still needed to determine the most appropriate dose ranges for the autistic population for many of the drugs reviewed here. Fourth, because adverse effects are more likely to occur in the autistic population, discussion of medications with families should include adverse effects as well as how to monitor, decrease, or ameliorate these adverse effects. For example, risperidone has an adverse effect of weight gain, which raises concerns for all the health risks related to obesity. However, risperidone but may be the best pharmacological choice for the patient and should not be disregarded if adverse effects can be controlled through changes in dose, scheduling, and environmental factors. Other medications may cause more serious threats, and caretakers must be educated as to how to monitor for these adverse effects. In nonverbal children or children with communication difficulties, adverse effects can be challenging to recognize, monitor, and treat, and as a result, caregiver education is paramount. …because adverse effects are more likely to occur in the autistic population, discussion of medications with families should include adverse effects as well as how to monitor, decrease, or ameliorate these adverse effects. Finally, several pharmacological therapies have been evaluated in lower quality studies and therefore provide researchers with an abundance of possible future research avenues. The atypical antipsychotic agents clozapine, ziprasidone, and aripiprazole, the antidepressants sertraline, paroxetine, citalopram, venlafaxine, and mirtazapine, the anti-seizure medication topiramate, the NMDA receptor antagonist Memantine, the NMDA receptor agonist D-cycloserine, and acetylcholinesterase inhibitors rivastigmine and galantamine, the anxiolytic/hypnotic buspirone, and the opioid antagonist naltrexone warrant further research in the treatment of autism symptoms in children. SummaryTo provide the best pharmacological treatment for children with autism, providers must identify target behaviors and weigh the benefits against the adverse effects in collaboration with caretakers and the patient. Children with autism present with an array of multidimensional symptoms and characteristics and will respond differently to various pharmacological therapies. As children with autism differ from child to child, so will successful interventions. The practitioner must weave his or her way through the symptoms, the goals of the caretakers, child responses, and educational, behavioral, and pharmacological interventions in order to provide successful treatment and optimize outcome. Research for drug efficacy in the autistic population has increased dramatically during the past 5 years, and researchers are on the cusp of finding many possible choices for the symptomatic treatment of autism. Unfortunately, core deficits and associated symptoms of autism are difficult to treat because the neuropathology of autism is not yet clear and the wide range of possible etiologies, symptoms, and presentations leads to speculation and somewhat untargeted interventions. Appropriate drug therapy can make a difference in the life of autistic children, but more research is desperately needed. In addition, appropriate pharmacotherapy treatments can help children with autism grow, adapt, and develop skills that will change their social, developmental, and cognitive outcome. Autistic children have the ability to move beyond society's low expectation of function and adaptation and can do so with the right help. ReferencesAman et al., 1995. 1.. Psychotropic and anticonvulsant drugs in subjects with autism: Prevalence and patterns of use. Journal of the American Academy of Child and Adolescent Psychiatry. 1995;34:1672–1681. Abstract | Full-Text PDF (977 KB) | CrossRef American Psychiatric Association, 1994. 2.. Diagnostic and statistical manual of mental disorders. 4th ed.. Washington, DC: American Psychiatric Association; 1994;. Arnold et al., 2006. 3. Atomoxetine for hyperactivity in autism spectrum disorders: Placebo-controlled crossover pilot trial. Journal of the American Academy of Child and Adolescent Psychiatry. 2006;45:1196–1205. Abstract | Full Text | Full-Text PDF (196 KB) | CrossRef Campbell et al., 1997. 4.. Neuroleptic-related dyskinesias in autistic children: A prospective, longitudinal study. Journal of the American Academy of Child and Adolescent Psychiatry. 1997;26:835–843. Centers for Disease Control and Prevention, 2007. 5.. CDC releases new data on autism spectrum disorders from multiple communities in the United States (CDC Media Relations). Retrieved March 21, 2007. from http://www.cdc.gov/od/oc/media/pressrel/2007/r070208.htm2007;. Eli Lilly, 2006. 6.. Zyprexa (package insert). Indianapolis, IN: Eli Lilly and Company; 2006;. Elia et al., 1991. 7.. Methylphenidate and dextroamphetamine treatments of hyperactivity: Are there true nonresponders?. Psychiatry Research. 1991;36:141–155. MEDLINE | CrossRef Food and Drug Administration, 2006. 8.. FDA approves the first drug to treat irritability associated with autism, Risperdal. FDA News. 2006;Retrieved December 30, 2006, from http://www.fda.gov/bbs/topics/NEWS/2006/NEW01485.html. Findling et al., 1997. 9.. An open clinical trial of risperidone monotherapy in young children with autistic disorder. Psychopharmacology Bulletin. 1997;33:155–159. MEDLINE Findling et al., 2004. 10. Quetiapine in nine youths with autistic disorder. Journal of Child and Adolescent Psychopharmacology. 2004;14:287–294. MEDLINE Fombonne, 2003. 11.. Epidemiological surveys of autism and other pervasive developmental disorders: An update. Journal of Autism and Developmental Disorders. 2003;33:365–382. MEDLINE | CrossRef Greenhill et al., 2001. 12. Impairment and deportment responses to different methylphenidate doses in children with ADHD: The MTA titration trial. Journal of the American Academy of Child and Adolescent Psychiatry. 2001;40:180–187. Abstract | Full Text | Full-Text PDF (126 KB) | CrossRef Gringras, 2000. 13.. Practical paediatric psychopharmacological prescribing in autism: The potential and the pitfalls. Autism. 2000;4:229–247. CrossRef Handen et al., 2000. 14.. Efficacy of methylphenidate among children with autism and symptoms of attention-deficit hyperactivity disorder. Journal of Autism and Developmental Disorders. 2000;30:245–255. MEDLINE | CrossRef Hellings et al., 2005. 15. A double-blind, placebo-controlled study of valproate for aggression in youth with pervasive developmental disorders. Journal of Child and Adolescent Psychopharmacology. 2005;15:682–692. MEDLINE | CrossRef Hollander et al., 2005. 16. A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism. Neuropsychopharmacology. 2005;30:582–589. CrossRef Hollander et al., 2005. 17.. Divalproex sodium vs. placebo in the treatment of repetitive behaviors in autism spectrum disorder. International Journal of Neuropsychopharmacology. 2005;9:209–213. MEDLINE | CrossRef Hollander et al., 2006. 18. A double-blind placebo-controlled pilot study of olanzapine in childhood/adolescent pervasive developmental disorder. Journal of Child and Adolescent Psychopharmacology. 2006;16:541–548. MEDLINE | CrossRef King et al., 2001. 19. Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder. Journal of the American Academy of Child and Adolescent Psychiatry. 2001;40:658–665. Abstract | Full Text | Full-Text PDF (155 KB) | CrossRef Lacy et al., 2006. 20.. Drug information handbook: A comprehensive resource for all clinicians and health care professionals. 14th ed.. Hudson, OH: Lexi-Comp, Inc; 2006;. Langworthy-Lam et al., 2002. 21.. Prevalence and patterns of use of psychoactive medicines in individuals with autism in the Autism Society of North Carolina. Journal of Child and Adolescent Psychopharmacology. 2002;12:311–321. MEDLINE Lecavalier, 2006. 22.. Behavioral and emotional problems in young people with pervasive developmental disorders: Relative prevalence, effects of subject characteristics, and empirical classification. Journal of Autism and Developmental Disorders. 2006;36:1101–1114. MEDLINE | CrossRef Malone et al., 2001. 23.. Olanzapine versus haloperidol in children with autistic disorder: An open pilot study. Journal of the American of Child and Adolescent Psychiatry. 2001;40:887–894. Malone et al., 2002. 24.. Risperidone treatment in children and adolescents with autism: Short- and long-term safety and effectiveness. Journal of the American Academy of Child and Adolescent Psychiatry. 2002;41:140–147. Abstract | Full Text | Full-Text PDF (171 KB) | CrossRef Martin et al., 2003. 25.. Low-dose Fluvoxamine treatment of children and adolescents with pervasive developmental disorders: A prospective, open-label study. Journal of Autism and Developmental Disorders. 2003;33:77–85. MEDLINE | CrossRef Martin et al., 1999. 26.. Open-label quetiapine in the treatment of children and adolescents with autistic disorder. Journal of Child and Adolescent Psychopharmacology. 1999;9:99–107. MEDLINE | CrossRef McDougle et al., 1997. 27. Risperidone treatment of children and adolescents with pervasive developmental disorders: A prospective, open-label study. Child and Adolescent Psychiatry. 1997;26:685–693. McDougle, 2004. 28.. Ask the Editor. Journal of Autism and Developmental Disorders. 2004;34:593–594. MEDLINE | CrossRef McDougle et al., 2005. 29. Risperidone for the core symptom domains of autism: Results from the study by the Autism Network of the Research Units on Pediatric Psychopharmacology. American Journal of Psychiatry. 2005;162:1142–1148. CrossRef Owley et al., 2006. 30. A prospective, open-label trial of memantine in the treatment of cognitive, behavioral, and memory dysfunction in pervasive developmental disorders. Journal of Child and Adolescent Psychopharmacology. 2006;16:517–524. MEDLINE | CrossRef Owley et al., 2005. 31. An open-label trial of escitalopram in pervasive developmental disorders. Journal of the American Academy of Child and Adolescent Psychiatry. 2005;44:343–348. Abstract | Full Text | Full-Text PDF (100 KB) | CrossRef Perry et al., 1997. 32.. Risperidone in children and adolescents with pervasive developmental disorder: Pilot trial and follow-up. Journal of Child and Adolescent Psychopharmacology. 1997;7:167–179. MEDLINE | CrossRef Posey et al., 2006. 33.. The use of serotonin reuptake inhibitors in autism and related disorders. Journal of Child and Adolescent Psychopharmacology. 2006;16:181–186. MEDLINE | CrossRef Posey et al., 2006. 34.. Open-label atomoxetine for attention-deficit/hyperactivity disorder symptoms associated with higher-functioning pervasive developmental disorders. Journal of Child and Adolescent Psychopharmacology. 2006;16:599–610. MEDLINE | CrossRef Research Units on Pediatric Psychopharmacology Autism Network, 2002. 35.. Risperidone in children with autism and serious behavioral problem. New England Journal of Medicine. 2002;347:314–321. CrossRef Research Units on Pediatric Psychopharmacology Autism Network, 2005a. 36.. Risperidone treatment of autistic disorder: Longer-term benefits and blinded discontinuation after 6 months. American Journal of Psychiatry. 2005;162:1361–1369. CrossRef Research Units on Pediatric Psychopharmacology Autism Network, 2005b. 37.. Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Archives of General Psychiatry. 2005;62:1266–1274. CrossRef Scahill et al., 2006. 38. A prospective open trial of guanfacine in children with pervasive developmental disorders. Journal of Child and Adolescent Psychopharmacology. 2006;16:589–598. MEDLINE | CrossRef Scahill et al., 2001. 39. A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention-deficit hyperactivity disorder. American Journal of Psychiatry. 2001;158:1067–1074. CrossRef Taketomo et al., 2006. 40.. Lexi-Comp's pediatric dosage handbook. 13th ed.. Hudson, OH: Lexi-Comp Inc; 2006;. Wasserman et al., 2006. 41. Levetiracetam versus placebo in childhood and adolescent autism: A double-blind placebo-controlled study. International Clinical Psychopharmacology. 2006;21:363–367. MEDLINE | CrossRef West and Waldrop, 2006. 42.. Risperidone use in the treatment of behavioral symptoms in children with autism. Pediatric Nursing. 2006;32:545–549. MEDLINE Lis West, Pediatric Nurse Practitioner, Carolina Pediatric Group, Fayetteville, NC. Julee Waldrop, Clinical Associate Professor, University of North Carolina, Chapel Hill, NC. Susan Brunssen, Assistant Professor, University of North Carolina, Chapel Hill, NC.
PII: S0891-5245(08)00394-5 doi:10.1016/j.pedhc.2008.12.001 © 2009 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.
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Pharmacologic Treatment for the Core Deficits and Associated Symptoms of Autism in Children
