Risperidone in autism- Dr Kalpana Shekawat


Published on

To determine the efficacy and safety of risperidone for people with autism spectrum disorder& to
study benefits of low dosage Risperidone in Autism

Published in: Health & Medicine
1 Like
  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Risperidone in autism- Dr Kalpana Shekawat

  1. 1. Risperidone inAutismPaper by Dr Kalpana Shekhawat 10/5/2011Ruptech Educational IndiaTo determine the efficacy and safety of risperidone for people with autism spectrum disorder&to study benefits of low dosage Risperidone in Autism.
  2. 2. ObjectivesTo determine the efficacy and safety and tolerability of risperidone for people with autismspectrum disorder& to study benefits of low dosage Risperidone in Autism.Risperidone is a drug used in Psychiatric Medicine to treat cases of Schizophrenia, a form ofinsanity. It acts on certain specific receptors on the brain that help to modify the behavior ofpersons so afflicted.Exact cause of Autism is not known but is believed to be multi factorial, with a strong geneticinfluence.There is a 60-90% concordance rate for monozygotic twins and a 0% concordance rate for dizygotic twins. The genetic component of Autism is heterogeneous attributed to as many as100 genes and genetic abnormalities in Autism have been identified in mitochondrial genesand in all chromosomes except 14 and 20. It is believed that multiple genes interact withvaried environmental causes to produce the disorders, and that the causative genes may varyfrom one population to another. Because of the complex heterogeneity and the variablebehavioral phenotype of Autism, linkage studies have not identified specific chromosomalregions that are universally believed to harbor the genes causing it is initiated by at least 6 to7 major genes and about 3 to 4 times that number of minor genes, causing a wide variety ofmedical pathologies. One of those genes that may have something to do with the presence ofthe HOXA1 gene coupled with the presence of mercury in the body. The metal getsincorporated into the neural proteins to cause their dysfunction. This causes thecharacteristic abnormal dissociated behavior patterns seen in children with Autism Spectrumdisorder.Limitations:Limited resources were available therefore a very small control group.Exclusion criteria: Children with known allergy to Risperidone Liver & Kidney disorder Juvenile diabetesInclusion Criteria: Age 5-16 years Only diagnosed autistics by a Pediatric Neurologist.Material Required: Syp Risinia (prescribed by their pediatrician)
  3. 3. Sample Size:Planned 60 children, reduced to 4 children (2girls and 2boys) due to limited resources available.ABSTRACTBackground:Autistic children presents with psychiatric symptoms, pharmacotherapy is sometimes used toameliorate target behaviors. The behaviors include hyper activity, tantrums, and physicalaggression, self-injurious behavior, stereotypies, and anxiety symptoms, especially obsessive-compulsive behaviors. The older neuroleptics were limited in their usefulness because oftheir tendency to produce extrapyramidal symptoms and tardive dyskinesia. Open-label trialsof atypical neuroleptics (risperidone, olanzapine) have shown effectiveness in treating thesebehaviors, and in some instances, have also improved social relatedness.Naltrexone, an opiate antagonist was also originally touted as useful, especially for self-injurious behavior, but its utility has not yet been proven. Clomipramine, a tricyclicantidepressant that inhibits serotonin reuptake, has demonstrated usefulness in reducingcompulsions and stereotypies in autistic children. However, it does lower the seizurethreshold, can cause agranulocytosis, and has cardio toxic and behavior toxicity effects. Othermedications used to treat psychiatric symptoms in autistic children include stimulants,selective serotonin reuptake inhibitors (SSRIs), and clonidine. The SSRIs, in particular, appearto be somewhat effective in diminishing hyperactive, agitated, and obsessive-compulsivebehaviors although there have not yet been sufficient, controlled studies regarding theirutility.Autistic spectrum disorder encompasses a wide variety of behavioral and communicativeproblems. Both the core features and non-core features of autism have been targeted in avariety of therapies. Atypical antipsychotic medications, including risperidone, have been usedfor symptom and behavior improvement and have shown beneficial outcomes, particularly incertain aspects of the disorder. However, given the nature of the condition presenting in youngpatients, the risks of these potentially long term therapies must be weighed against thebenefits.Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors,have advantages over traditional antipsychotic medications in the treatment of adults withschizophrenia and may be beneficial in children with autistic disorder who have seriousbehavioral disturbances. However, data on the safety and efficacy of atypical antipsychoticagents in children are limited.Risperidone:
  4. 4. DRUG CLASS AND MECHANISM:Risperidone is an atypical antipsychotic drug that is used for treating schizophrenia, bipolarmania and autism. Other atypical antipsychotic drugs include Olanzapine (Zyprexa), Quetiapine(Seroquel), Ziprasidone (Geodon), Aripiprazole (Abilify) and paliperidone (Invega). Atypicalantipsychotics differ from typical antipsychotics due to the lesser degree of extrapyramidal(movement) side effects and constipation.The mechanism of action of risperidone is like other anti-psychotics, risperidone affects the waythe brain works by interfering with communication among the brains nerves. Nervescommunicate with each other by making and releasing chemicals called neurotransmitters. Theneurotransmitters travel to other nearby nerves where they attach to receptors on the nerves.The attachment of the neurotransmitters either stimulates or inhibits the function of thenearby nerves. Risperidone blocks several of the receptors on nerves including dopamine type2, serotonin type 2, and alpha 2 adrenergic receptors. It is believed that many psychoticillnesses are caused by abnormal communication among nerves in the brain and that by alteringcommunication through neurotransmitters, risperidone can alter the psychotic state.Risperidone was approved by the FDA in December, 1993.PRESCRIPTION: YesPREPARATIONS: Tablets: 1, 2, 3, and 4 mg. Suspension: 1 mg/ml. Orally disintegrating tablets:1, 2, 3, and 4 mg.STORAGE: Tablets should be kept at room temperature, 15-25 C (59-77 F).PRESCRIBED FOR:Risperidone is used to treat schizophrenia, bipolar mania [as a sole therapy or combinationtherapy with lithium (Eskalith, Lithobid) or valproate (Depakene, Depacon) Clinical studiesinvolving small numbers of patients have shown some benefit in using risperidone for stutteringand Tourette syndrome (non FDA-approved uses). Another non-FDA approved use ofrisperidone is for obsessive-compulsive disorders.DOSING:
  5. 5. Risperidone can be prescribed once or twice daily. Initial dosing is generally 2 mg/day. Doseincreases can occur in increments of 1-2 mg/day, as tolerated, to a recommended dose of 4-8mg/day. In children, risperidone should be initiated at 0.5 mg once daily, and can be increasedin increments of 0.5 or 1 mg/day, as tolerated, to a recommended dose of 2.5 mg/day.Risperidone can be given with or without meals. The recommended dose of Risperdal Consta is25 mg injected into the deltoid or gluteal muscle every two weeks. Patients who have neverreceived risperidone are started on oral risperidone in order to evaluate tolerability. Patientsthen may be transitioned to Risperdal Consta if oral risperidone is toleratedDRUG INTERACTIONS: Risperidone may interfere with elimination by the kidneys of clozapine(Clozaril), a different type of antipsychotic medication, causing increased levels of clozapine inthe blood. This could increase the risk of side effects with clozapine.Serotonin reuptake inhibitors such as paroxetine(Paxil), Sertraline (Zoloft), and fluoxetine(Prozac) when taken with risperidone causes the metabolism (breakdown) of risperidone by theliver to be inhibited, which in turn causes elevated blood levels of risperidone, and mayincrease the risk of adverse reactions.Antifungal drugs such as fluconazole (Diflucan), itraconazole (Sporanox), and ketoconazole(Nizoral) when taken with risperidone cause the metabolism (breakdown) of risperidone by theliver to be inhibited, which in turn causes elevated blood levels and may increase the risk ofadverse reactions.PREGNANCY: There are no adequate studies of risperidone in pregnant women. Someunwanted effects have been reported in animal studies. Risperidone can be used in pregnancyif the physician feels that the benefits outweigh the potential but unknown risks.NURSING MOTHERS: Risperidone is excreted in human breast milk. Women receivingrisperidone should not breastfeed.ADVERSE EFFECTS: The most commonly adverse effects associated with risperidone are extrapyramidal effects (sudden, often jerky, involuntary motions of the head, neck, arms, body, oreyes), dizziness, hyperactivity, tiredness, abdominal pain, fatigue, fever and nausea.Risperidone may cause a condition called orthostatic hypotension during the early phase oftreatment (the first week or two). Patients who develop orthostatic hypotension have a drop intheir blood pressure when they rise from a lying position and may become dizzy or even loseconsciousness.Studies involving risperidone suggest an increased risk of hyperglycemia-related adversereactions as seen in diabetes. Although there is no clear link between risperidone and diabetes,patients should be tested during treatment for elevated blood sugars. Additionally, personswith risk factors for diabetes, including obesity or a family history of diabetes, should have theirfasting levels of blood sugar tested before starting treatment and periodically throughout
  6. 6. treatment to detect the onset of diabetes. Any patient developing symptoms that suggestdiabetes during treatment should be tested for diabetes.USES: Risperidone is used to treat certain mental/mood disorders (such as schizophrenia, manicphase of bipolar disorder, occasionally irritability associated with autistic disorder). Thismedication can help us to think clearly and function in daily life. This is a psychiatric medication(antipsychotic-type) that works by helping to restore the balance of certain natural substancesin the brain (neurotransmitters).This medication may also be used in combination with othermedication to treat depression.Autism the problem and EpidemiologyThe autism spectrum, also called autism spectrum disorders (ASD) or autism spectrumconditions (ASC), with the adjective autistic sometimes replacing the noun autism, is aspectrum of psychological conditions characterized by widespread abnormalities of socialinteractions and communication, as well as restricted interests and repetitive behavior.Autism forms the core of the autism spectrum disorders. Asperger syndrome is closest toautism. People with Asperger syndrome have no significant delay in language developmentPDD-NOS is diagnosed when the criteria are not met for a more specific disorder. Some sourcesalso include Rett syndrome and childhood disintegrative disorder which share several signs withautism but may have unrelated causes; other sources combine ASD with these two conditionsinto the pervasive developmental disorders.Autism characteristicsThe defining characteristics of autism spectrum disorders are qualitative impairments of socialcommunication and interaction, along with restricted and repetitive activities and interests.Individual symptoms occur in the general population and appear not to associate highly,without a sharp line separating pathological severity from common traits other aspects of ASD,such as atypical eating, are also common but are not essential for diagnosis; they can affect theindividual or the family.An estimated 0.5% to 10% of individuals with ASD show unusual abilities, ranging from splinterskills such as the memorization of trivia to the extraordinarily rare talents of prodigious autisticsavantsMaking and maintaining friendships often proves to be difficult for children with autism. Forthem, the quality of friendships, not the number of friends, predicts how lonely they are,
  7. 7. despite the common belief that they prefer to be alone. Being on the autism spectrum does notkeep children from understanding race and gender stereotypes in a society; like normalchildren they can learn aspects of stereotypical behavior by observing their parents actions.Autism therapiesThe main goals of treatment are to lessen associated deficits and family distress, and toincrease quality of life and functional independence. No single treatment is best and treatmentis typically modified to the childs needs. rigorous, sustained special education programs andbehavior therapy early in life can help children acquire self-care, social, and job skills. Availableapproaches include applied behavior analysis (ABA), developmental models, structuredteaching, speech and language therapy, social skills therapy, and occupational therapy ABAtherapy has a strong research base but it maybe limited by diagnostic severity and IQ.In a recent study by Russo et al., researchers at Albert Einstein College of Medicine of YeshivaUniversity have provided new evidence that, children with autism spectrum disorders (ASD)process sensory information including sound, touch and vision differently to typicallydeveloping children. This research provides support for decades of clinical and anecdotalobservations by occupational therapists practicing sensory integration therapy that individualswith ASD have difficulty coping with multiple sources of sensory information. These findingsoffer an opportunity for occupational therapists to develop objective measures to facilitatemore empirical evaluation and understanding of sensory processing disorders and sensoryintegration therapyEpidemiology of autismThe prevalence rate of all pervasive developmental disorders appears to be 58.7 per 10000children. This prevalence rate includes Autism (22/10000), Asperger syndrome (11/10000),Pervasive developmental disorder not otherwise specified (24.8/10000) and child disintegrativedisorder (0.9/10000).this is consistent with previous research that identified all pervasivedevelopment disorders as (60/10000).this incidence of diagnosis of autism may have increased.there is evidence that increased in the number of children identified with autism is likelyrelated to changes in the definition of and diagnostic criteria for autism, as well asimprovements in the recognition of autism at younger ages. An increase in the availability ofdiagnostic services, treatment facilities, professionals trained in childhood developmentaldisorders has greatly increased the capacity of the healthcare system to identify and treatchildren with autistic spectrum disorder at younger age.Methods:
  8. 8. Random trail of risperidone in 4 children diagnosed with ASD as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior in children 5 to 16 years old. The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement (CGI-I) scale at eight weeks, data were recorded. Dosage: Risinia syrup 1mg bi daily Procedure: In this study 4 children were identified, who were already on risperidone in dosage (1mg bidaily) prescribed by their pediatricians. Each child was assessed for severe tantrum, aggression, self injurious behavior etc, primary outcome measures were the scores on the irritability subscale of the Aberrant behavior checklist and the rating on the Clinical Global Impression-Improvement(CGI-I) scale at 8 weeks. Report Study result of effect of Risperidone in children with Autism Time period – 8 weeks, 10th Dec 10 to 4th Feb 11 Dose of medicine-1mg/BID as prescribed by their pediatricians. Age groups-5-8yrs Total no. of Age group Boys Girls Risperidone Placebo children given given 4 5-8yrs 2 2 2 2 Outcome of Therapy Out come Scale earlier Scale with Scale with measures Risperidone Placebo Irritability score 4 2 4 Clinical Global 4 3 4 ImpressionImprovement scale Weight gain 0 4 1Increased Appetite 0 3 0 Fatigue 1 4 1.5-2
  9. 9. Drowsiness 0 3 1 Dizziness 0 2 0 Drooling 0 0 0*Criteria’s measured at a scale of 1-5Adverse events in 2 children with Autism who responded to Risperidone in an 8 weekstrial. Number of children Adverse Event moderate or severe event Moderate Severe Nasal congestion 2 0 Appetite increase 2 0 Coughing 0 0 Anxiety 0 0 Difficulty falling asleep 0 0 Fever 0 0 Skin irritation 0 0 Vomiting 0 0 Accidental injury 0 0 Constipation 0 0 Drowsiness/sedation 2 0 Enuresis 0 0 Headache 0 0 Hyper salivation 0 0 Sore throat 0 0 Depression 0 0 Diarrhea 0 0 Difficulty urinating 0 0
  10. 10. Dyskinesia 0 0 Earache 0 0 Restlessness/agitation 0 0 Sinus condition 0 0 Stomach /abdominal discomfort 0 0 Tiredness/fatigue 2 0 Tremor 0 0 Weight gain 2 0 Muscle rigidity 0 0 Other 0 0Clinical Global Impression (CGI) Improvement Ratings for 2 children with Autism, whoresponded to Risperidone in 8 weeks trial: Rating Week 0 Week 4 Week 8 Very much improved 0 0 1 Much improved 0 0 1 Minimally improved 0 2 0 No change 2 0 0 Worse 0 0 0 (much worse) 0 0 0 Total 2 2 2Discussion
  11. 11. Risperidone may be well-tolerated and effective treatment for up to 6 months for children withautism complicated by tantrums, aggression, and self-injury. As measured by the primaryindices of response, the CGI improvement scale and the Aberrant Behavior Checklist irritabilitysubscale, improvements associated with risperidone administration were maintained with verygood tolerability. Furthermore, gradual substitution of placebo for risperidone was associatedwith a greater return of aggression, temper outbursts, and self-injurious behavior than in thesubjects who continued to receive risperidone in the discontinuation phase. Risperidone maybe an efficacious treatment for short- and intermediate-term management of seriousbehavioral problems in children with autism.As in our study of short-term risperidone efficacy risperidone was also associated withcontinued maintenance of improvements on the Aberrant Behavior Checklist subscales forhyperactivity, stereotypic behavior, and lethargy/social withdrawal.The largest extended study of neuroleptic treatment for autistic disorder was the examinationof the effects of haloperidol over a 6-month period. In that study 60 children treated with amean dose of 1.23 mg/day of haloperidol were classified as "good responders." After 6 monthsof treatment, 33 (63%) of 52 subjects were rated as "much improved." Autism factor ratingsderived from the Children’s Psychiatric Rating Scale obtained on entry and at 6 months showedan average decline of 23% from baseline. Upon abrupt withdrawal of haloperidol, only 14% ofthe children were rated as much worse and 50% showed at least mild deterioration.In an open-label prospective study of risperidone for 11 children with autistic disorder, Zuddaset al. noted that 10 of the 11 showed enduring improvement over the 12-month observationperiod. Another open trial of risperidone enrolled 22 subjects with autistic disorder. Of these,15 subjects showed significant improvement at a mean dose of 1.2 mg/day for up to 7 monthsof treatment. Additional published observations include positive responses maintained over a4-month period in responders and improvement maintained during a 2-year treatment historyin two adults with autistic disorder It should be noted that few earlier studies defined specificentry criteria for aggression or disruptive behavior, but, taken together, the available accountssuggest that risperidone’s benefit for aggression, severe tantrums, and self-injuryaccompanying autistic disorder persisted over these intermediate treatment periods (6–12months), although additional long-term treatment data focusing on managing severe andchallenging behaviors are clearly needed.A key clinical question concerns the length of continued treatment with risperidone for thisclinical indication. The return of aggression, tantrums, and agitation was there in the placebogroup as in the subjects who continued to take risperidone. 1 of 2 children in the placebo groupdid not relapse during the 2-month discontinuation period, demonstrating some degree ofvariability in outcome. It is conceivable that more gradual drug tapering may have moderatedthe observed relapse in the risperidone group or that dose reduction, rather than completemedication discontinuation, may have been sufficient to maintain treatment gains. It is alsoconceivable that concomitant behavioral treatment reinforcing replacement behaviors couldprotect against relapse following risperidone withdrawal. Nevertheless, the high rate of relapse
  12. 12. observed in our study suggests caution when withdrawal of effective treatment for these targetsymptoms is considered. At a minimum, clinicians should document a clear period of stablefunctioning before initiating medication taper and ensure that appropriate psychosocialsupports are in place to minimize relapse risk. No factors predicting relapse were identifiablegiven the modest number of subjects in the discontinuation phase of this study, but theycertainly form an important future research question. Longer-term follow-up information onoutcome may help make decisions about maintenance treatment.Although adverse events associated with risperidone exposure were observed to be common inthis study, most were not deemed clinically significant, and many were not attributed torisperidone. No cases of dyskinesia were observed during treatment or upon withdrawal. Theabsence of dyskinesia in this study may be noteworthy given the report by Campbell andcolleagues that 30% of 118 subjects showed dyskinesia following withdrawal of haloperidolafter a similar duration of treatment, although the more gradual taper used in this study may beresponsible for the finding. Weight gain associated with treatment was significant and some,especially since antipsychotic-related weight gain has been associated with diabetes and otheradverse outcomes. Longer-term observations to determine the clinical significance of weightgain as well as other adverse events are needed to evaluate the risk-benefit ratio for risperidonetreatment in children with autistic disorder.There were several limitations in this investigation. First, although the data collection period inthis phase of the study spanned up to a maximum total of 8 weeks of risperidone exposure, thisdoes not completely mimic clinical practice, as many patients receive treatments likerisperidone for longer time periods. Also, there was no systematic effort to reduce or constrainindividual daily doses over time, leaving some uncertainty about the lowest possible long-termdose. This limitation notwithstanding, the relatively low mean dose (approximately 2.0 mg/day)of risperidone used in this study was effective in managing the specific target symptoms ofaggression, agitation, and self-injury. This mean dose was remarkably similar to the doses inseveral other studies .The possibility of solidifying these gains or even extending the benefit ofrisperidone treatment by combining it with behavior therapy was not explored in thisinvestigation but is an important research question for future studies. Finally, the safetyobservations of the study were limited to a maximum of 8 weeks of risperidone exposure in arelatively very small study group. Thus, our data may be insufficient to estimate precisely thelong-term risks of risperidone in children.In summary, intermediate-length treatment with risperidone appeared to be associated withthe maintenance of reductions in aggression, agitation, self-injury, and irritability from short-term treatment. There was little evidence of accommodation to the effects of risperidone, andthe medication appeared to be well tolerated in a group of children and adolescents withautistic disorder. Additional studies on predictors of stable improvement, longer-term safety,and approaches combining other interventions are of interest.Conclusion:
  13. 13. Risperidone may be well-tolerated and may be effective at treating behavioral symptomsassociated with pervasive developmental disorders (PDD) and autism, according to the resultsof a trial conducted on 4 children with confirmed diagnosis of PDD.Risperidone can be beneficial in some features of autism. However there are limited dataavailable from our study with small sample size, limited inferences. In addition, long-termfollow-up is also lacking. Further research is necessary to determine the efficacy of risperidonein clinical practice.The main limitation of this study is the less number of children in control group and shortduration of follow up.However it is concluded that the drug Risperidone is a beneficial drug for children in the Autismspectrum disorder and more research on a large span of patients will produce more concreteresults towards reaching more effective handling of ASD.References: 1. Chakrabarti S, Fombonne E: Pervasive developmental disorders in preschool children. JAMA 2001; 285:3093–3099[Abstract/Free Full Text] 2. Rutter M, Silberg J, O’Connor T, Simonoff E: Genetics and child psychiatry, II: empirical research findings. J Child Psychiatry 1999; 40:19–55 3. Anderson LT, Campbell M, Adams P, Small AM, Perry R, Shell J: The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children. J Autism Dev Disord 1989; 19:227–239[CrossRef][Medline] 4. McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Carroll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Vitiello B, Ritz L, Davies M, Robinson J, McMahon D (Research Units on Pediatric Psychopharmacology Autism Network): a double-blind, placebo-controlled trial of risperidone in children with autistic disorder. N Engl J Med 2002; 347:314– 321[CrossRef][Medline] 5. Perry R, Campbell M, Adams P, Lynch N, Spencer EK, Curren EL, Overall JE: Long-term efficacy of haloperidol in autistic children: continuous versus discontinuous drug administration. J Am Acad Child Adolesc Psychiatry 1989; 28:87–92[Medline]
  14. 14. 6. McDougle CJ, Scahill L, McCracken JT, Aman MG, Tierney E, Arnold LE, Freeman BJ, Martin A, McGough JJ, Cronin P, Posey DJ, Riddle MA, Ritz L, Swiezy NB, Vitiello B, Volkmar FR, Votolato NA, Walson P: Research Units on Pediatric Psychopharmacology (RUPP) Autism Network: background and rationale for an initial controlled study of risperidone. Child Adolesc Psychiatr Clin N Am 2000; 9:201–224[Medline]7. McDougle CJ, Holmes JP, Carlson DC, Pelton GH, Cohen DJ, Price LH: A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders. Arch Gen Psychiatry 1998; 55:633– 641[Abstract/Free Full Text]8. Fisman S, Steele M: Use of risperidone in pervasive developmental disorders: a case series. J Child Adolesc Psychopharmacol 1996; 6:177–190[Medline]9. Scahill L, McCracken J, McDougle CJ, Aman M, Arnold LE, Tierney E, Cronin P, Davies M, Ghuman J, Gonzalez N, Koenig K, Lindsay R, Martin A, McGough J, Posey DJ, Swiezy N, Volkmar F, Ritz L, Vitiello B: Methodological issues in designing a multisite trial of risperidone in children and adolescents with autism. J Child Adolesc Psychopharmacol 2001; 11:377–388[CrossRef][Medline]10. Lord C, Rutter M, Le Couteur A: Autism Diagnostic Interview—Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 1994; 24:659–685[CrossRef] Medline11. Lord C, Pickles A, McLennan J, Rutter M, Bregman J, Folstein S, Fombonne E, Leboyer M, Minshew N: Diagnosing autism: analyses of data from the Autism Diagnostic Interview. J Autism Dev Disord 1997; 27:501–517[CrossRef][Medline]12. Carter AS, Volkmar FR, Sparrow SS, Wang JJ, Lord C, Dawson G, Fombonne E, Loveland K, Mesibov G, Schopler E: The Vineland Adaptive Behavior Scales: supplementary norms for individuals with autism. J Autism Dev Disord 1998; 28:287–302[CrossRef][Medline]13. Arnold LE, Aman MG, Martin A, Collier-Crespin A, Vitiello B, Tierney E, Asarnow R, Bell- Bradshaw F, Freeman BJ, Gates-Ulanet P, Klin A, McCracken JT, McDougle CJ, McGough JJ, Posey DJ, Scahill L, Swiezy NB, Ritz L, Volkmar F: Assessment in multisite randomized clinical trials of patients with autistic disorder: the Autism RUPP [Research Units on Pediatric Psychopharmacology] Network. J Autism Dev Disord 2000; 30:99–11114. Aman MG, Singh NN: Aberrant Behavior Checklist—Community: Supplementary Manual. East Aurora, NY, Slosson Educational Publications, 199415. Brown EC, Aman MG, Havercamp SM: Factor analysis and norms for parent ratings on the Aberrant Behavior Checklist—Community for young people in special education. Res Dev Disabil 2002; 23:45–60[CrossRef][Medline]
  15. 15. 16. Guy W (ed): ECDEU Assessment Manual for Psychopharmacology: Publication ADM 76– 338. Washington, DC, US Department of Health, Education, and Welfare, 197617. Arnold LE, Vitiello B, McDougle C, Scahill L, Shah B, Gonzalez NM, Chuang S, Davies M, Hollway J, Aman MG, Cronin P, Koenig K, Kohn AE, McMahon DJ, Tierney E: Parent- defined target symptoms respond to risperidone in RUPP Autism Network Study: a customer approach to clinical trials. J Am Acad Child Adolesc Psychiatry 2003; 42:1443– 1450[CrossRef][Medline]18. Simpson GM, Angus JWS: A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 1970; 212:11–19[Medline]19. Gibbons RD, Hedeker D, Elkin I, Waternaux C, Kraemer HC, Greenhouse JB, Shea MT, Imber SD, Sotsky SM, Watkins JT: Some conceptual and statistical issues in analysis of longitudinal psychiatric data: application to the NIMH Treatment of Depression Collaborative Research Program dataset. Arch Gen Psychiatry 1993; 50:739– 750[Abstract/Free Full Text]20. Martin A, Scahill L, Anderson GM, Aman M, Arnold LE, McCracken J, McDougle CJ, Tierney E, Chuang S, Vitiello B, Research Units on Pediatric Psychopharmacology Autism Network: Weight and leptin changes among risperidone-treated youths with autism: 6- month prospective data. Am J Psychiatry 2004; 161:1125–1127[Abstract/Free Full Text]21. Zuddas A, Di Martino A, Muglia P, Cichetti C: Long-term risperidone for pervasive developmental disorder: efficacy, tolerability, and discontinuation. J Child Adolesc Psychopharmacol 2000; 10:79–90[Medline]22. Malone RP, Maislin G, Choudhury MS, Gifford C, Delaney MA: Risperidone treatment in children and adolescents with autism: short- and long-term safety and effectiveness. J Am Acad Child Adolesc Psychiatry 2002; 41:140–147[CrossRef][Medline]23. Masi G, Cosenza A, Mucci M, Brovedani P: Open trial of risperidone in 24 young children with pervasive developmental disorders. J Am Acad Child Adolesc Psychiatry 2001; 40:1206–1214[CrossRef][Medline]24. Dartnall NA, Holmes JP, Morgan SN, McDougle CJ: Brief report: two-year control of behavioral symptoms with risperidone in two profoundly retarded adults with autism. J Autism Dev Disord 1999; 29:87–91[CrossRef]Medline25. Pappadopulos E, Macintyre JC, Crismon ML, Findling RL, Malone RP, Derivan A, Schooler N, Sikich L, Greenhill L, Schur SB, Felton CJ, Kranzler H, Rube DM, Sverd J, Finnerty M, Ketner S, Siennick SE, Jensen PS: Treatment recommendations for the use of antipsychotics for aggressive youth (TRAAY), part II. J Am Acad Child Adolesc Psychiatry 2003; 42:145–161[CrossRef][Medline]
  16. 16. 26. Campbell M, Armenteros JL, Malone RP, Adams PB, Eisenberg ZW, Overall JE: Neuroleptic-related dyskinesias in autistic children: a prospective, longitudinal study. J Am Acad Child Adolesc Psychiatry 1997; 36:835–843[CrossRef][Medline]27. Findling RL, Maxwell K, Wiznitzer M: An open clinical trial of risperidone monotherapy in young children with autistic disorder. Psychopharmacol Bull 1997; 33:155–159[Medline]28. Buitelaar JK, van der Gaag RJ, Cohen-Kettenis P, Melman CT: A randomized controlled trial of risperidone in the treatment of aggression in hospitalized adolescents with subaverage cognitive abilities. J Clin Psychiatry 2001; 62:239–248[Medline]