Please select the eligibility criteria that correspond to the clinical trial below.
Title: Placebo-Controlled Study of Risperidone for the Treatment of Children and Adolescents With Autism and Negative Behavioral Symptoms
Brief Summary: This study is designed to determine the effectiveness of risperidone, a drug treatment for the interfering symptoms of Autistic Disorder in children and adolescents between the ages of 5 and 17. Between 100 and 120 patients will be participating in this research study at five academic medical centers in the United States. The primary aim of the treatment is to reduce impairing behavioral symptoms such as aggression, explosive outbursts, or self-injurious behavior, without significant side effects. A secondary aim is to evaluate possible improvement in the level of social relatedness, attention, motor coordination, and short-term memory.

This study is a placebo-controlled, double-blind study (neither the investigators nor patients know if the treatment being given is risperidone or an inactive substance, placebo). Patients will be asked to participate for 6 to 8 months. For the first 8 weeks, patients will receive either risperidone or placebo, randomly chosen. At the end of the 8 weeks, those patients who have improved and were on risperidone will be asked to continue on this medication for another 4 months. The last two months of the study are again double-blind (neither patients nor investigators know treatment). Patients will either continue risperidone treatment or be gradually tapered from risperidone (placebo-substitution). This blinded discontinuation phase will last 2 months during which patients will be closely monitored for recurrence or worsening of symptoms. Patients who have been treated with placebo in the first 8 weeks of the study and have not improved will be treated with risperidone. Weekly visits are required for the first 8 weeks of the study, monthly visits for the following 4 months, and weekly visits during the last 2 months of the study.


Options:
A: Inclusion Criteria:

1. Completed at least 12 weeks of exposure to study drug in lead-in study MEM-MD-91 (NCT01592786)
2. Met responder criterion at two consecutive visits separated by at least two weeks in lead-in study MEM-MD-91
3. Provide written informed assent, when developmentally appropriate, to participate in the study before conduct of any study-specific procedures. The parent/guardian/LAR must provide written informed consent before the patient's participation in the study. A separate written informed consent for the caregiver must also be obtained before the conduct of any study specific procedures
4. Have a knowledgeable caregiver who is capable of providing reliable information about the patient's condition, attending all clinic visits with the patient, and overseeing the administration of study drug. Every effort should be made to maintain the same caregiver as used in the lead-in study throughout this study
5. Have normal results from the physical examination, laboratory tests, ECG, and vital signs at Visit 1 of this study (last visit of Study MEM-MD-91). Any abnormal findings must be deemed not clinically significant by the Investigator and documented
6. Be able to speak and understand English sufficiently (or their native language if this can be accommodated by the site), as well as have a caregiver and parent/guardian/LAR who is able to speak and understand English sufficiently (or their native language if this can be accommodated by the site), to comprehend the nature of the study and to allow for the completion of all study assessments
7. Have a family that is sufficiently organized and stable to guarantee adequate safety monitoring and continuous attendance to clinic visits for the duration of the study
8. Females who are 9 years and older or who have had onset of menses must have a negative urine pregnancy test at Visit 1
9. Age of 6 years to 12 years at the time of entry into lead in study MEM-MD-91

Exclusion Criteria:

1. Patients with a concurrent medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger the patient's well being
2. Significant risk of suicidality based on the Investigator's judgment, the Aberrant Behavior Checklist-Irritability subscale (ABC-I), or if appropriate, as indicated by a response of "yes" to questions 4 or 5 in the suicidal ideation section of the Children's C-SSRS (Columbia-Suicide Severity Rating Scale) or any suicidal behavior.
3. Patients with evidence or history of malignancy (other than excised basal cell carcinoma) or any significant hematologic, endocrine, cardiovascular (including any rhythm disorder), neurologic, respiratory, renal, hepatic, or gastrointestinal disease
4. Female patients of child-bearing potential who are not using or not willing to use a conventional method of contraception approved by the PI. Abstinence is an acceptable method of contraception
5. Patients requiring treatment with prohibited concomitant medications
6. Patients who, in the opinion of the Investigator, might not be suitable for the study
7. Employee or immediate relative of an employee of Forest Laboratories, Inc., any of its affiliates or partners, or the study center
B: Inclusion Criteria:

* Meets DSM-IV, ADI-R criteria for autistic disorder.
* Age 5-17 years.
* Outpatients
* Parent or legal guardian willing to sign informed consent.

Exclusion Criteria:

* Subject has been diagnosed with a psychotic disorder (such as schizophrenia) or a mood disorder, including depression or bipolar disorder (manic depression).
* Subject has caused visible harm to him/herself.
* Subject has an active seizure disorder or epilepsy (seizures within the past year).
* Subject has an unstable medical illness, including heart disease.
* Subject has experienced brain injury.
* Subject has a history of diabetes.
* Subject reports significant improvement of autism symptoms and behaviors to current medication or other therapies.
* Subject has a history of prior treatment with Aripiprazole of 5 mg/day or higher for 6 weeks.
* Subject lives in a far away area and/or does not have regular access to transportation to the clinical facility.
* Subject is a pregnant female or unwilling to use acceptable contraception if sexually active.
C: Inclusion Criteria

1. Male or female outpatients 6 to 12 years of age
2. Verbal; Module 2 or 3 on Autism Diagnostic Observation Schedule (ADOS)
3. Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) for Autism Spectrum Disorder. The diagnosis will be confirmed with Autism Diagnostic Interview-Revised (ADI-R) and ADOS Module 2 or 3.
4. Parents report difficulties with motor skills
5. Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Screening and Baseline
6. If already receiving stable nonpharmacologic educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening and will not electively initiate new or modify ongoing interventions for the duration of the study
7. Participants can be on up to 2 concomitant psychotropic medications before entering the study, provided that they have been on a stable dose for 30 days and have no plans to adjust the dose for the duration of study
8. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigators
9. Prior to the conduct of any study-specific procedures, the patient must provide assent to participate in the study (if developmentally appropriate), and the parent or legal guardian must provide written informed consent
10. The patient and the patient's parent or legal guardian must be able to speak and understand English sufficiently to understand the nature of the study and to allow for the completion of all study assessments
11. The parent or legal guardian must be capable of providing reliable information about the patient's condition, agree to oversee the administration of study drug, and accompany the patient to all clinic visits

Exclusion Criteria:

1. Patients born prior to 35 weeks gestational age
2. Patients with any primary psychiatric diagnosis other than autism at Screening: a history of Attention Deficit Hyperactivity Disorder (ADHD), bipolar disorder, psychosis, post-traumatic stress disorder, schizophrenia, or major depressive disorder
3. Patients with a medical history of neurological disease, including, but not limited to, epilepsy/seizure disorder (except simple febrile seizures), movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes, or known abnormal MRI/structural lesion of the brain
4. Patients with a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease.
5. Patients who plan to initiate or change pharmacological or nonpharmacologic interventions during the course of the study
6. Patients on d-cycloserine or riluzole as they both target the glutamate system
7. Patients on agents that alkalinize the urine (acetazolamide, potassium citrate, and sodium bicarbonate), as they decrease the elimination of memantine
8. Patients who have received treatment with memantine in the past with no response
9. Patients with a history of hypersensitivity reaction to dextromethorphan, amantadine, or any other NMDA receptor antagonists
10. Patients unable to tolerate venipuncture procedures for blood sampling
11. Patients who, in the Investigator's opinion, might not be suitable for the study
12. Children weighing under 20 kg (to meet FDA approvals)
13. Patients with a positive pregnancy test
D: Inclusion Criteria:

* Males and females between the ages of 5 and 17 years 2 months.
* Weight of 15 kg or greater.
* DSM-IV diagnosis of Autistic Disorder.
* Inpatient or outpatient.
* Medication free for at least 2 weeks for all psychotropic medications (4 weeks for fluoxetine or depot neuroleptics).
* Anticonvulsants used for treatment of seizure disorder permitted if the dosage has been stable for 4 weeks and patient seizure free for at least 6 months.
* Clinical Global Impression Severity score of at least 4 and a)18 or greater on the Irritability Scale of the Aberrant Behavior Checklist or b) .5 total score on the Ritvo-Freeman scale.
* Mental age of at least 18 months.
* Negative pregnancy test

Exclusion Criteria:

* IQ below 18 months.
* Females with a positive pregnancy test. - Evidence of a prior adequate trial with risperidone.
* Evidence of hypersensitivity to risperidone.
* Past history of neuroleptic malignant syndrome.
* DSM-IV diagnosis of Pervasive Developmental Disorder other than Autistic Disorder.
* Significant medical condition such as heart disease, hypertension, liver or renal failure, pulmonary disease, or unstable seizure disorder.
* Weight less than 15 kg.

Answer: D