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Risperidone Treatment of Autistic Disorder: Longer-Term
Benefits and Blinded Discontinuation After 6 Months
Research Units on
Objective: Risperidone is effective for
Results: Part I included 63 children. The
Pediatric Psychopharmacology
per outbursts, and self-injurious behavior Autism Network
behaviors may be chronic, there is a need the Aberrant Behavior Checklist irritability subscale was small and clinically insignifi- longer-term treatment with this agent.
cant. Reasons for discontinuation of part Iincluded loss of efficacy (N=5) and ad- Method: The authors conducted a mul-
an average of 5.1 kg. Part II included 32 patients. The relapse rates were 62.5% for for continued risperidone; this difference 8-week trial. Part I consisted of 4-monthopen-label treatment with risperidone, Conclusions: Risperidone showed per-
starting at the established optimal dose; sistent efficacy and good tolerability for havior Checklist irritability subscale and was associated with a rapid return of dis- (Am J Psychiatry 2005; 162:1361–1369)
Autistic disorder is characterized by impaired social finity of medicines such as risperidone for 5-HT recep- interaction, abnormal language development, and repet- tors, especially those of the 5-HT2A and 5-HT2C classes itive and restricted patterns of behavior (DSM-IV), and it (6). Until 2002, only one placebo-controlled study of ris- affects as many as 20 people per 10,000 (1, 2). Children peridone in adults with autism (7) and a handful of open- with autism display broad differences in abilities and label studies of children with pervasive developmental needs, but accompanying maladaptive behaviors such as disorders (8) had been published. In a prior report, we self-injurious behavior, aggression, and tantrums are described the short-term efficacy of risperidone over pla- common and frequently severe enough to limit educa- cebo in an 8-week controlled trial for 101 children and tional and developmental progress. A variety of treat- adolescents with autistic disorder (4). Risperidone was ments, including medication, are employed in the man- chosen for study given the greatest preliminary evidence agement of these maladaptive behaviors. Controlled for its efficacy in this population (6, 8). Although the ef- trials of medication treatment of autism are limited, but fects of risperidone on aggression, tantrums, and self-in- evidence provides support for both conventional and jurious behavior were substantial in our short-term study, atypical antipsychotic agents (3, 4). Among studies of the the question of whether these improvements would en- conventional antipsychotics, well-controlled trials of ha- loperidol have revealed statistically significant effects, In this study, subjects who showed a positive response but only modest clinical benefits, in children with autism, to risperidone in the short-term trial were enrolled in an and short- and longer-term side effects are of concern (3, 5).
additional 4-month open-label trial (total drug exposure= Atypical antipsychotics appear to be preferred by clinicians 6 months), which was followed by a placebo-controlled because of the perception that atypicals have a more fa- discontinuation protocol lasting up to 8 weeks. The aim of vorable side effect profile than typical neuroleptics, but the study was threefold: first, to determine if the short- few direct comparison data exist. Atypical agents are also term efficacy of risperidone is maintained over time; sec- of interest because of possible serotonin (5-HT) abnor- ond, to determine if the side effect burden of risperidone malities in some individuals with autism and the high af- remains acceptable over an extended treatment period; RISPERIDONE AND AUTISM
TABLE 1. Baseline Characteristics of Children With Autism Who Responded to Risperidone in an 8-Week Trial and Did or
Did Not Participate in a 4-Month Open-Label Extension

Scores on Vineland Adaptive Behavior Scales Scores on Aberrant Behavior Checklist subscales Clinical Global Impression severity score a The sum of the numbers of subjects may not be the same as the total number because data were missing for some variables.
b Nearly significant difference between groups (χ2=6.94, df=3, p<0.08).
c Nearly significant difference between groups (t=1.74, df=99, p<0.09).
d Significant difference between groups (t=2.03, df=99, p<0.05).
and third, to examine the feasibility of risperidone discon- included intelligence testing, the Vineland Adaptive Behavior tinuation after 6 months of treatment.
Scales (12, 13), routine laboratory tests, an electrocardiogram,measurements of height, weight, and vital signs, a medical his-tory, and a physical examination. All subjects were also required to manifest clinically significant problems consisting of aggres-sion, tantrums, and/or self-injury as defined by a score of 18 or Setting and Subjects
higher on the irritability subscale of the Aberrant Behavior This study was an extension of the 8-week double-blind, pla- Checklist—Community version (14, 15) rated by the parent (or cebo-controlled trial with parallel groups and the 8-week open- primary caretaker) and confirmed by clinician review. Scores on label risperidone treatment offered to placebo nonresponders.
this 15-item subscale range from 0 to 45, with higher scores indi- These short-term trials were conducted by the Autism Network cating greater pathology. In addition, the subjects were required of the National Institute of Mental Health (NIMH) Research to receive a score of moderate or higher on the Clinical Global Units on Pediatric Psychopharmacology between June 1999 and Impression (GCI) severity scale (16, pp. 218–222) from the exam- April 2001. The five clinical sites included the University of Cali- fornia at Los Angeles, Ohio State University, Indiana University, Eligible subjects were randomly assigned to receive risperi- Yale University, and Kennedy Krieger Institute ( Johns Hopkins done or placebo for 8 weeks; details are provided elsewhere (4).
University). The protocol was approved by the institutional re- The primary outcome measures were the parent-rated irritability view board at each site and the NIMH Data and Safety Monitor- subscale of the Aberrant Behavior Checklist and the clinician- ing Board, and written informed consent was obtained from a rated CGI improvement scale. Subjects showing a 25% reduction parent or guardian prior to enrollment. Safety and protocol on the irritability subscale and a rating of much improved or very fidelity were monitored through weekly conference calls involv- much improved on the CGI improvement scale by the blinded ing the principal investigators and study coordinators, through clinical evaluator were classified as positive responders and were quarterly reviews by the Data and Safety Monitoring Board, and eligible for the 4-month open-label extension phase. At the end of through annual site visits by the coordinating center ( Yale the 4-month extension, responders were eligible for the random- ized discontinuation phase. In the discontinuation phase, relapse This study enrolled 63 of the 101 subjects in the first protocol, was defined as a 25% increase in the score on the parent-rated Ab- all of whom met criteria for autistic disorder as defined in DSM- errant Behavior Checklist irritability subscale and a CGI improve- IV. Other entry criteria (at the time of enrollment in the initial ment rating of much worse or very much worse, compared to the double-blind phase) included 1) age of 5–17 years, 2) significant prediscontinuation baseline, for at least 2 consecutive weeks, as tantrums, aggression, self-injurious behavior, and/or agitation, 3) absence of significant medical problems and any other psychiat- Secondary parent-rated outcome measures included the four ric disorder requiring drug therapy (e.g., bipolar disorder, psycho- additional subscales of the Aberrant Behavior Checklist: lethargy/ sis), 4) weight of at least 15 kg, and 5) mental age of at least 18 social withdrawal, stereotypic behavior, hyperactivity, and inap- months. No concomitant treatment with psychotropic medica- propriate speech. At baseline, the parents were interviewed to tion was allowed during any phase of the study, except anticon- identify the child’s target symptoms and to rate compulsive be- vulsant treatment for seizure control if the child had been taking haviors on the Children’s Yale-Brown Obsessive Compulsive Scale a stable dose for 4 weeks and had been free of seizures for 6 (see references 4, 13, and 17 for details on study assessment).
months (see reference 9 for a detailed description).
Medication Dosing
Protocol Schedule and Design
The medication schedule in the initial 8-week trial was based At the final visit of the initial 8-week controlled study, or the 8- on the child’s weight and clinical response. The maximum risperi- week open-label risperidone treatment for placebo nonre- done dose was 2.5 mg/day for children between 15 and 45 kg and sponders, subjects deemed responders were offered enrollment 3.5 mg/day for children weighing above 45 kg. Dose reductions to in the extension protocol. Written informed consent for contin- manage side effects were allowed at any time. During the 4- ued participation was obtained from the parents, and for 10 sub- month open phase, clinicians were allowed to adjust the total jects deemed to have the capacity to consent, assent was ob- daily dose according to response and/or adverse events, with the tained. The subjects were then seen every 4 weeks for 4 monthsfor assessment of efficacy, safety, and possible need for dose ad- total daily dose increased up to a maximum of 3.5 mg/day for justments. At the end of these 4 months of open-label treatment, children weighing 15–45 kg and up to 4.5 mg/day for children subjects who continued to show a positive response entered the discontinuation phase. In this phase, the subjects were randomly Safety Monitoring
assigned again, this time either to continued risperidone at thesame dose or to gradual placebo substitution, in a double-blind The routine laboratory tests, electrocardiogram, and physical fashion. The discontinuation reduced the maintenance dose by examination were repeated at entry into the extension phase and 25% per week. Thus, the dose was 75% of the week 16 dose for 1 prior to the discontinuation. Weight and vital signs were as- week, followed by 50% of the week 16 dose for the second week, sessed at each visit. At each visit, the primary clinician asked the 25% of the week 16 dose for the third week, and placebo only by parents about the child’s health complaints, intercurrent illness, the fourth week. All subjects were seen weekly for a total of 8 and concomitant medications, and the clinician administered a 32-item checklist concerning the child’s energy level, musclestiffness, motor restlessness, bowel and bladder habits, sleep, Baseline Assessment and Measurement of Outcome
and appetite. Neurological side effects were further assessed at At screening for participation in the initial 8-week treatment each visit with the Simpson-Angus Rating Scale (18) and the Ab- study, autistic disorder was ascertained through a history and ex- normal Involuntary Movements Scale (AIMS) (16, pp. 534–537).
amination by a research team and was corroborated by the Au- Adverse events indicated by any of these methods were docu- tism Diagnostic Interview—Revised (10), administered by a clini- mented according to severity, duration, attribution, outcome, cian trained to reliability (11). The screening measures also RISPERIDONE AND AUTISM
TABLE 2. Scores on Subscales of the Aberrant Behavior
FIGURE 1. Scores on the Irritability Subscale of the Aber-
Checklist for 63 Children With Autism Who Responded to
rant Behavior Checklist for 63 Children With Autism Who
Risperidone in an 8-Week Trial and Participated in a 4-
Responded to Risperidone in an 8-Week Trial and Partici-
Month Open-Label Extension
pated in a 4-Month Open-Label Extension
ritability Subscale
a Week 0 corresponds to the end of the initial 8 weeks of medication b For patients who discontinued treatment, the last observation was rant Behavior Chec 10
Statistical Analysis
Mean Scor
Open-label trial. The statistical tests were two-tailed with alpha
set at 0.05. To evaluate differences between subjects who partici-
pated in the extension trial and those who did not, we compared
demographic and clinical characteristics by t tests for continuous variables and chi-square tests for categorical variables. All sub- jects who enrolled in the extension trial were included in an in-tent-to-treat analysis. The monthly scores on the parent-rated a Week 0 corresponds to the end of the initial 8 weeks of medication subscales (irritability, lethargy, stereotypy, hyperactivity, and in- appropriate speech) of the Aberrant Behavior Checklist were ana- For patients who discontinued treatment, the last observation wascarried forward.
lyzed with mixed effects linear regression models in which time,site, and site-by-time interaction were the fixed effects (19). Theaverage slope of the regression line (change in irritability score or the efficacy analysis. During the data analysis, three sub- score on other subscale) was calculated for each individual across jects were noted to have entered the extension phase time. In addition, the distribution of CGI improvement scores wascalculated across time.
without fully meeting the response criteria. Inclusion ofthese three subjects did not alter the results, and thus Discontinuation phase. As originally planned in the protocol,
interim analyses were performed for the Data and Safety Moni-
they were included in all analyses. Demographic charac- toring Board after the first 16 and 32 subjects completed this teristics of the entire 63 subjects in the extension study phase of the study (9). These interim analyses were reviewed only are shown in Table 1. When compared to the 38 subjects by the Data and Safety Monitoring Board, independently of the who did not participate in the extension phase, the ex- study investigators. Chi-square analysis with Yates’s correction tension group showed few differences. Of a total of 24 was used to compare the rates of relapse in the two groups. Toevaluate the time to relapse and the probability of relapse, the log comparisons, only one variable, the baseline score on the rank survival analysis of continued drug versus placebo and the Aberrant Behavior Checklist hyperactivity subscale, dif- fered significantly, being slightly higher at baseline in thesubjects continuing in the extension study.
4-Month Open-Label Treatment: Outcomes
Baseline Characteristics
A total of 51 subjects (81.0%) completed the 16-week Of the original 101 subjects (82 boys and 19 girls) en- open-label treatment period. Of the 12 dropouts from the rolled in the short-term trial, 63 subjects (mean age=8.6 extension study, five subjects were withdrawn because of years, SD=2.8) showed a positive response to risperidone loss of efficacy, one was withdrawn because of noncompli- and consented to participate in the extension protocol.
ance with the protocol, one withdrew because of an ad- Of these 63 subjects, 30 were classified as responders verse event (constipation), one withdrew consent (no during the double-blind trial and 30 were so classified in longer interested in medication treatment), and four were the 8-week open-label risperidone trial for placebo non- lost to follow-up. The mixed effects regression model for responders. There were no differences in scores on the ir- all 63 subjects in the intent-to-treat analysis revealed a sig- ritability subscale of the Aberrant Behavior Checklist or nificant time effect for the irritability subscale of the Aber- in the distribution of CGI severity scores at the baseline rant Behavior Checklist (Table 2, Figure 1). However, the of the extension phase between subjects who entered di- mean irritability ratings showed only a minor increase rectly from the double-blind study and those who en- across the 16-week extension phase, from a mean score of tered from the 8-week open-label trial for placebo nonre- 9.5 (SD=6.8) at the start to 10.8 (SD=7.1) at week 16 (Figure sponders. Therefore, the two groups were combined in 1), in contrast to the mean pretreatment irritability score RUPP AUTISM NETWORK
TABLE 3. Clinical Global Impression (CGI) Improvement Ratings for 63 Children With Autism Who Responded to Risperi-
done in an 8-Week Trial and Participated in a 4-Month Open-Label Extension

a Week 0 corresponds to the end of the initial 8 weeks of medication exposure.
of 26.6 (SD=7). This 1-point increase lacks clinical signifi- tion phase and the remainder of the 63 subjects, aside cance. Indeed, after 16 weeks of treatment the mean score from the discontinuation subjects’ again showing higher still showed a 59% reduction from the mean rating at the mean baseline scores on the Aberrant Behavior Checklist initiation of risperidone treatment 6 months before, a per- hyperactivity factor (mean=34.4, SD=8.7, versus mean= cent reduction identical to that seen after the initial 8- 30.6, SD=9.0; t=2.08, df=99, p=0.04). Also, subjects in the week double-blind study and yielding an effect size of discontinuation phase showed higher mean baseline d>1.0. Analysis of the CGI improvement ratings at end- scores on the Aberrant Behavior Checklist irritability factor point showed that 82.5% of the subjects (N=52) continued than the remaining 63 subjects (mean=27.6, SD=6.1, versus to be rated as much improved or very much improved (1 mean 24.8, SD=7.7, t=2.02, df=99, p=0.05). As planned, the or 2 on the CGI improvement scale) (Table 3). By contrast, NIMH Data and Safety Monitoring Board independently only 7.9% were rated as worse or much worse compared to reviewed two interim efficacy analyses, first after the ini- tial 16 subjects completed this phase and again after the The risperidone doses were also examined to determine first 32 subjects finished. The relapse rate after 32 subjects whether a dose increase is required to ensure stability of completed this phase was significantly higher in the pla- treatment effects. The mean risperidone doses were 1.96, cebo-treated group (62.5%, N=10) than in the group re- 1.80, 1.87, 2.10, and 2.08 mg/day for weeks 0, 4, 8, 12, and ceiving continued risperidone (12.5%, N=2) (Yates’s cor- 16, respectively, representing a modest 6% increase over rected χ2=6.53, df=1, p=0.01). The median survival time, i.e., time to relapse, was 34 days for the placebo-treated Secondary outcome measures included the other sub- subjects versus 57 days for those continuing to take ris- scales of the Aberrant Behavior Checklist. Table 2 shows peridone (Figure 2). On the basis of the results of this scores on those subscales and results of the random re- planned interim analysis, the NIMH Data and Safety Monitoring Board ruled that the discontinuation phasebe stopped immediately. The four subjects who were still 4-Month Open-Label Treatment: Adverse Events
in this phase of the protocol exited the study and were Adverse events, especially mild to moderate increased treated clinically. Exploratory post hoc analyses were per- appetite, tiredness, and/or drowsiness, were common (Ta- formed in an effort to identify any clinical predictors of re- ble 4). Only one subject withdrew because of an adverse lapse. Age, initial Aberrant Behavior Checklist irritability event (constipation). Although the parents of six subjects score, and IQ all failed to differ significantly (p>0.30) be- (9.5%) reported “abnormal movements,” no dyskinesias tween the relapsing and nonrelapsing subjects.
were identified on repeated examination with the AIMSand Simpson-Angus scale by a physician. One subject with Discussion
preexisting obesity had galactorrhea according to themother’s report, but this was not observed on examina- Data from this study suggest that risperidone is a well- tion. Compared to their weight at the initiation of risperi- tolerated and effective treatment for up to 6 months for done treatment, the subjects showed a 6-month weight in- children with autism complicated by tantrums, aggres- crease of 5.1 kg (SD=3.6) (paired t=7.46, df=31, p<0.001), sion, and self-injury. As measured by the primary indices which was significantly greater (p<0.001) than the amount of response, the CGI improvement scale and the Aberrant expected on the basis of available developmental norms.
Behavior Checklist irritability subscale, improvements as- This finding has been reviewed in more detail in a separate sociated with risperidone administration were main- tained in over 80% of the subjects, with very good tolera-bility. Furthermore, gradual substitution of placebo for Discontinuation Phase
risperidone was associated with a greater return of aggres- A total of 38 subjects were enrolled in the discontinua- sion, temper outbursts, and self-injurious behavior than tion phase. Few differences in baseline characteristics in the subjects who continued to receive risperidone in were observed between the subjects in the discontinua- the discontinuation phase. Taken together, these data RISPERIDONE AND AUTISM
TABLE 4. Adverse Events in 63 Children With Autism Who Responded to Risperidone in an 8-Week Trial and Participated
in a 4-Month Open-Label Extension

a Mild events are not reported. The most severe event is reported if the child reported the event more than once. One subject reportedly ex- strongly suggest that risperidone is an efficacious treat- In an open-label prospective study of risperidone for 11 ment for short- and intermediate-term management of children with autistic disorder, Zuddas et al. (21) noted serious behavioral problems in children with autism.
that 10 of the 11 showed enduring improvement over the As in our study of short-term risperidone efficacy (4), 12-month observation period. Another open trial (22) of risperidone was also associated with continued mainte- risperidone enrolled 22 subjects with autistic disorder. Of nance of improvements on the Aberrant Behavior Check- these, 15 subjects showed significant improvement at a list subscales for hyperactivity, stereotypic behavior, and mean dose of 1.2 mg/day for up to 7 months of treatment.
Additional published observations include positive re- lethargy/social withdrawal. In addition, the mean reduc- sponses maintained over a 4-month period in responders tion from baseline in the irritability subscale scores of 59% (23) and improvement maintained during a 2-year treat- at the last observation in the extension phase was nearly ment history in two adults with autistic disorder (24). It identical to that observed in the risperidone group at the should be noted that few earlier studies defined specific completion of the 8-week double-blind efficacy trial.
entry criteria for aggression or disruptive behavior, but, These data expand the limited published database on taken together, the available accounts suggest that risperi- extended treatment of autistic disorder with medication.
done’s benefit for aggression, severe tantrums, and self-in- Heretofore, the largest extended study of neuroleptic jury accompanying autistic disorder persisted over these treatment for autistic disorder was the examination of the intermediate treatment periods (6–12 months), although effects of haloperidol over a 6-month period. In that study additional long-term treatment data focusing on manag- (5), 60 children treated with a mean dose of 1.23 mg/day of ing severe and challenging behaviors are clearly needed.
haloperidol were classified as “good responders.” After 6 A key clinical question concerns the length of continued months of treatment, 33 (63%) of 52 subjects were rated as treatment with risperidone for this clinical indication. On “much improved.” Autism factor ratings derived from the one hand, the return of aggression, tantrums, and agita- Children’s Psychiatric Rating Scale obtained on entry and tion was five times as great in the placebo-substitution at 6 months showed an average decline of 23% from base- group as in the subjects who continued to take risperi- line. Upon abrupt withdrawal of haloperidol, only 14% of done. On the other hand, 37.5% (six of 16) of the children the children were rated as much worse and 50% showed at in the placebo-substitution group did not relapse during the 2-month discontinuation period, demonstrating some RUPP AUTISM NETWORK
degree of variability in outcome. It is conceivable that FIGURE 2. Survival Analysis for Children With Autism Who
more gradual drug tapering may have moderated the ob- Responded to Risperidone and Were Then Randomly As-
signed to Placebo or Continued Risperidone for 8 Weeksa

served relapse in the risperidone group or that dose reduc-tion, rather than complete medication discontinuation, may have been sufficient to maintain treatment gains. It is also conceivable that concomitant behavioral treatment reinforcing replacement behaviors could protect againstrelapse following risperidone withdrawal. Nevertheless, the high rate of relapse observed in our study suggestscaution when withdrawal of effective treatment for these target symptoms is considered. At a minimum, cliniciansshould document a clear period of stable functioning be-fore initiating medication taper (25) and ensure that ap- propriate psychosocial supports are in place to minimize maining Stable

relapse risk. No factors predicting relapse were identifi- able given the modest number of subjects in the discon- tinuation phase of this study, but they certainly form an important future research question. Longer-term follow-up information on outcome may help clinicians make de- cisions about maintenance treatment. To this end, we arein the process of obtaining 18-month safety data for ourstudy group.
Although adverse events associated with risperidone exposure were observed to be common in this study, most Days in Randomized Discontinuation Phase
were not deemed clinically significant, and many were not a For the placebo group, the risperidone dose was decreased by 25% attributed to risperidone. It is important that only one per week. Relapse was defined as a 25% increase in the score on theAberrant Behavior Checklist irritability subscale and a CGI improve- subject withdrew from the 4-month open-label treatment ment rating of much worse or very much worse, compared to the because of an adverse event, and no cases of dyskinesia prediscontinuation baseline, for at least 2 consecutive weeks. The were observed during 6 months of treatment or upon difference between groups was significant (test for equality of sur-vival distributions for treatment, log rank=6.89, df=1, p=0.009).
withdrawal. The absence of dyskinesia in this study isnoteworthy given the report by Campbell and colleagues(26) that 30% of 118 subjects showed dyskinesia following doses in several other studies (16, 22, 27, 28). The possibil- withdrawal of haloperidol after a similar duration of treat- ity of solidifying these gains or even extending the benefit ment, although the more gradual taper used in this study of risperidone treatment by combining it with behavior may be responsible for the finding. Weight gain associated therapy was not explored in this investigation but is an im- with treatment was significant and in some, but not all, portant research question for future studies. Finally, the cases posed a concern (20), especially since antipsychotic- safety observations of the study were limited to a maxi- related weight gain has been associated with diabetes and mum of 8 months of risperidone exposure in a relatively other adverse outcomes. Longer-term observations to de- small study group. Thus, our data may be insufficient to termine the clinical significance of weight gain as well as estimate precisely the long-term risks of risperidone in other adverse events are needed to evaluate the risk-bene- fit ratio for risperidone treatment in children with autistic In summary, intermediate-length treatment with ris- peridone appeared to be associated with the maintenance There were several limitations in this investigation.
of reductions in aggression, agitation, self-injury, and irri- First, although the data collection period in this phase of tability from short-term treatment. There was little evi- the study spanned up to a maximum total of 8 months of dence of accommodation to the effects of risperidone, and risperidone exposure, this does not completely mimic the medication appeared to be well tolerated in a group of clinical practice, as many patients receive treatments like children and adolescents with autistic disorder. Additional risperidone for longer time periods. Also, there was no sys- studies on predictors of stable improvement, longer-term tematic effort to reduce or constrain individual daily doses safety, and approaches combining other interventions are over time, leaving some uncertainty about the lowest pos- sible long-term dose. This limitation notwithstanding, therelatively low mean dose (approximately 2.0 mg/day) of Acknowledgments
risperidone used in this study was effective in managing The following are the authors of this report listed by role and the specific target symptoms of aggression, agitation, and study site: Ohio State University, principal investigator Michael G.
self-injury. This mean dose was remarkably similar to the Aman, Ph.D., co-investigators L. Eugene Arnold, M.Ed., M.D., RISPERIDONE AND AUTISM
Ronald Lindsay, M.D., Patricia Nash, M.D., Jill Hollway, B.A.; Uni- 6. McDougle CJ, Scahill L, McCracken JT, Aman MG, Tierney E, Ar- versity of California at Los Angeles, principal investigator James T.
nold LE, Freeman BJ, Martin A, McGough JJ, Cronin P, Posey DJ, McCracken, M.D., co-investigators Bhavik Shah, M.D., James Mc- Riddle MA, Ritz L, Swiezy NB, Vitiello B, Volkmar FR, Votolato Gough, M.D., Pegeen Cronin, Ph.D., Lisa Lee, B.A.; Indiana Uni- NA, Walson P: Research Units on Pediatric Psychopharmacol- versity, principal investigator Christopher J. McDougle, M.D., co- ogy (RUPP) Autism Network: background and rationale for an investigators David Posey, M.D., Naomi Swiezy, Ph.D., Arlene initial controlled study of risperidone. Child Adolesc Psychiatr Kohn, B.A.; Yale University, principal investigator, Lawrence Sca- hill, M.S.N., Ph.D., co-investigators Andres Martin, M.D., Kath- 7. McDougle CJ, Holmes JP, Carlson DC, Pelton GH, Cohen DJ, Price leen Koenig, M.S.N., Fred Volkmar, M.D., Deirdre Carroll, M.S.N., LH: A double-blind, placebo-controlled study of risperidone in Allison Lancor, B.S.; Kennedy Krieger Institute, principal investi- adults with autistic disorder and other pervasive developmen- gator Elaine Tierney, M.D., co-investigators Jaswinder Ghuman, tal disorders. Arch Gen Psychiatry 1998; 55:633–641 M.D., Nilda Gonzalez, M.D., Marco Grados, M.D.; National Insti- 8. Fisman S, Steele M: Use of risperidone in pervasive develop- tute of Mental Health, principal investigator Benedetto Vitiello, mental disorders: a case series. J Child Adolesc Psychopharma- M.D., co-investigator Louise Ritz, M.B.A.; Columbia University, statistician Mark Davies, M.P.H.; Nathan Kline Institute, data 9. Scahill L, McCracken J, McDougle CJ, Aman M, Arnold LE, Tier- management James Robinson, M.Ed., Don McMahon, M.S.
ney E, Cronin P, Davies M, Ghuman J, Gonzalez N, Koenig K,Lindsay R, Martin A, McGough J, Posey DJ, Swiezy N, Volkmar F, Received Oct. 23, 2003; revision received Sept. 22, 2004; accepted Ritz L, Vitiello B: Methodological issues in designing a multisite Oct. 1, 2004. From the Research Units on Pediatric Psychopharma- trial of risperidone in children and adolescents with autism. J cology Autism Network (individual contribuors are listed in Acknowl- Child Adolesc Psychopharmacol 2001; 11:377–388 edgments). Address correspondence and reprint requests to Dr. Mc- 10. Lord C, Rutter M, Le Couteur A: Autism Diagnostic Interview— Cracken, UCLA Neuropsychiatric Institute, 760 Westwood Plaza, Los Revised: a revised version of a diagnostic interview for caregiv- Angeles, CA 90024-1759; (e-mail). ers of individuals with possible pervasive developmental disor- Supported by NIMH contracts N01 MH-70010 (principal investiga- ders. J Autism Dev Disord 1994; 24:659–685 tor: Dr. McCracken), N01 MH-70009 (principal investigator: Dr. Sca- 11. Lord C, Pickles A, McLennan J, Rutter M, Bregman J, Folstein S, hill), N01 MH-70001 (principal investigator: Dr. McDougle), and N01 Fombonne E, Leboyer M, Minshew N: Diagnosing autism: anal- MH-80011 (principal investigator: Dr. Aman); by NIH Division of Re-search Resources General Clinical Research Center grants M01 RR- yses of data from the Autism Diagnostic Interview. J Autism Dev 00750 (to Indiana University), M01 RR-00052 (to Johns Hopkins Uni- versity), M01 RR-00034 (to Ohio State University), and M01 RR-06022 12. Carter AS, Volkmar FR, Sparrow SS, Wang JJ, Lord C, Dawson G, (to Yale University); by NIMH grant MH-01805 (to Dr. McCracken); and Fombonne E, Loveland K, Mesibov G, Schopler E: The Vineland by funding from the Korczak Foundation (to Dr. Scahill). Study medi- Adaptive Behavior Scales: supplementary norms for individu- cations were donated by Janssen Pharmaceutica. als with autism. J Autism Dev Disord 1998; 28:287–302 The authors thank the following members of the Autism Network of 13. Arnold LE, Aman MG, Martin A, Collier-Crespin A, Vitiello B, the NIMH Research Units on Pediatric Psychopharmacology Scientific Tierney E, Asarnow R, Bell-Bradshaw F, Freeman BJ, Gates-Ul- Advisory Board: C.T. Gordon, M.D., Joseph DeVeaugh-Geiss, M.D., Hen- anet P, Klin A, McCracken JT, McDougle CJ, McGough JJ, Posey rietta Leonard, M.D., Richard Shader, M.D., and Susan Swedo, M.D., fortheir contributions; the NIMH Data and Safety Monitoring Board and DJ, Scahill L, Swiezy NB, Ritz L, Volkmar F: Assessment in multi- Phillip Walson, M.D., for their comments and guidance; and Erin site randomized clinical trials of patients with autistic disorder: Kustan and Caifeng Fu for assistance in preparing this report.
the Autism RUPP [Research Units on Pediatric Psychopharma- The content of this publication does not necessarily reflect the cology] Network. J Autism Dev Disord 2000; 30:99–111 views or policies of the Department of Health and Human Services, 14. Aman MG, Singh NN: Aberrant Behavior Checklist—Commu- nor does mention of trade names, commercial products, or organi- nity: Supplementary Manual. East Aurora, NY, Slosson Educa- zations imply endorsement by the U.S. government.
15. Brown EC, Aman MG, Havercamp SM: Factor analysis and norms for parent ratings on the Aberrant Behavior Checklist— References
Community for young people in special education. Res DevDisabil 2002; 23:45–60 1. Chakrabarti S, Fombonne E: Pervasive developmental disor- 16. Guy W (ed): ECDEU Assessment Manual for Psychopharmacol- ders in preschool children. JAMA 2001; 285:3093–3099 ogy: Publication ADM 76–338. Washington, DC, US Depart- 2. Rutter M, Silberg J, O’Connor T, Simonoff E: Genetics and child ment of Health, Education, and Welfare, 1976 psychiatry, II: empirical research findings. J Child Psychiatry 17. Arnold LE, Vitiello B, McDougle C, Scahill L, Shah B, Gonzalez NM, Chuang S, Davies M, Hollway J, Aman MG, Cronin P, Koenig 3. Anderson LT, Campbell M, Adams P, Small AM, Perry R, Shell J: K, Kohn AE, McMahon DJ, Tierney E: Parent-defined target The effects of haloperidol on discrimination learning and be- symptoms respond to risperidone in RUPP Autism Network havioral symptoms in autistic children. J Autism Dev Disord Study: a customer approach to clinical trials. J Am Acad Child 4. McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, 18. Simpson GM, Angus JWS: A rating scale for extrapyramidal side Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, effects. Acta Psychiatr Scand Suppl 1970; 212:11–19 Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Car- 19. Gibbons RD, Hedeker D, Elkin I, Waternaux C, Kraemer HC, roll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Greenhouse JB, Shea MT, Imber SD, Sotsky SM, Watkins JT: Vitiello B, Ritz L, Davies M, Robinson J, McMahon D (Research Some conceptual and statistical issues in analysis of longitudi- Units on Pediatric Psychopharmacology Autism Network): a nal psychiatric data: application to the NIMH Treatment of De- double-blind, placebo-controlled trial of risperidone in chil- pression Collaborative Research Program dataset. Arch Gen dren with autistic disorder. N Engl J Med 2002; 347:314–321 5. Perry R, Campbell M, Adams P, Lynch N, Spencer EK, Curren EL, 20. Martin A, Scahill L, Anderson GM, Aman M, Arnold LE, Mc- Overall JE: Long-term efficacy of haloperidol in autistic chil- Cracken J, McDougle CJ, Tierney E, Chuang S, Vitiello B, Re- dren: continuous versus discontinuous drug administration. J search Units on Pediatric Psychopharmacology Autism Net- Am Acad Child Adolesc Psychiatry 1989; 28:87–92 work: Weight and leptin changes among risperidone-treated RUPP AUTISM NETWORK
youths with autism: 6-month prospective data. Am J Psychiatry 25. Pappadopulos E, Macintyre JC, Crismon ML, Findling RL, Ma- lone RP, Derivan A, Schooler N, Sikich L, Greenhill L, Schur SB, 21. Zuddas A, Di Martino A, Muglia P, Cichetti C: Long-term risperi- Felton CJ, Kranzler H, Rube DM, Sverd J, Finnerty M, Ketner S, done for pervasive developmental disorder: efficacy, tolerabil- Siennick SE, Jensen PS: Treatment recommendations for the ity, and discontinuation. J Child Adolesc Psychopharmacol use of antipsychotics for aggressive youth (TRAAY), part II. J Am Acad Child Adolesc Psychiatry 2003; 42:145–161 22. Malone RP, Maislin G, Choudhury MS, Gifford C, Delaney MA: 26. Campbell M, Armenteros JL, Malone RP, Adams PB, Eisenberg Risperidone treatment in children and adolescents with au- ZW, Overall JE: Neuroleptic-related dyskinesias in autistic chil- tism: short- and long-term safety and effectiveness. J Am Acad dren: a prospective, longitudinal study. J Am Acad Child Ado- Child Adolesc Psychiatry 2002; 41:140–147 23. Masi G, Cosenza A, Mucci M, Brovedani P: Open trial of risperi- 27. Findling RL, Maxwell K, Wiznitzer M: An open clinical trial of ris- done in 24 young children with pervasive developmental dis-orders. J Am Acad Child Adolesc Psychiatry 2001; 40:1206– peridone monotherapy in young children with autistic disor- der. Psychopharmacol Bull 1997; 33:155–159 24. Dartnall NA, Holmes JP, Morgan SN, McDougle CJ: Brief report: 28. Buitelaar JK, van der Gaag RJ, Cohen-Kettenis P, Melman CT: A two-year control of behavioral symptoms with risperidone in randomized controlled trial of risperidone in the treatment of two profoundly retarded adults with autism. J Autism Dev Dis- aggression in hospitalized adolescents with subaverage cogni- tive abilities. J Clin Psychiatry 2001; 62:239–248


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In July of 1968, Pope Paul VI issued a very important letter: "Humanae Vitae"(latin for Human Life). How many Catholics today know, love, live, and teach others it's truths? The New Universal Catechism calls contraception "intrinsically evil"(p.570) Contraception is against life. It goes against the natural design of God for sexuality, changing it into something it was never inten

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