Please select the eligibility criteria that correspond to the clinical trial below.
Title: Risperidone in the Treatment of Children and Adolescents With Autistic Disorder: A Double-Blind, Placebo-Controlled Study of Efficacy and Safety, Followed by an Open-Label Extension Study of Safety
Brief Summary: The purpose of this study is to evaluate the effectiveness (change in level of irritability and related behaviors) and safety and tolerability of the administration of 2 different fixed dose levels of risperidone (an atypical antipsychotic drug) compared with placebo in children or adolescents who have autism, and to evaluate the safety and tolerability of the drug for additional 26 weeks after the initial 6-week study period.


Options:
A: Inclusion Criteria:

* Male \& female subjects ages 8-18 years (inclusive).
* Diagnostic Statistical Manual (DSM)-5 Autism Spectrum Disorder (ASD) diagnostic criteria as established by clinical diagnostic interview
* At least moderate severity of social impairment as measured by a total raw score of ≥85 on the parent/guardian-completed Social Responsiveness Scale-Second Edition (SRS-2)14 and a score of ≥4 on the clinician-administered Clinical Global Impression-Severity scale (CGI-S)17.

Exclusion Criteria:

* IQ ≤70 based on the Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Vocabulary and Matrix Reasoning subtests
* Impaired communicative speech
* Subjects currently treated with the following medications (known to impact glutamate levels): Lamotrigine, Amantadine, N-acetylcysteine, D-cycloserine
* Subjects treated with a psychotropic medication not listed above on a dose that has not been stable for at least 4 weeks prior to study baseline.
* Co-administration of drugs that compete with memantine for renal elimination using the same renal cationic system, including hydrochlorothiazide, triamterene, metformin, cimetidine, ranitidine, quinidine, and nicotine
* Initiation of a new psychosocial intervention within 30 days prior to randomization.
* Subjects who are pregnant and/or nursing.
* Subjects with a history of non-febrile seizures without a clear and resolved etiology.
* Subjects with a history of or a current liver or kidney disease.
* Clinically unstable psychiatric conditions or judged to be at serious suicidal risk.
* Subjects who meet on the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-E) for alcohol or drug dependence or abuse. If the subject has a recent history of substance abuse, there will be a two-week washout period before initiating the trial as an added precaution. There are no known safety issues relating to memantine and recent history of substance abuse.
* Serious, stable or unstable systemic illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
* Subjects with severe hepatic impairment (LFTs \> 3 times ULN).
* Subjects with genitourinary conditions that raise urine pH (e.g., renal tubular acidosis, severe infection of the urinary tract).
* Known hypersensitivity to memantine.
* Severe allergies or multiple adverse drug reactions.
* A history of intolerance or adequate exposure to memantine, as determined by the clinician.
* Investigator and his/her immediate family defined as the investigator's spouse, parent, child, grandparent, or grandchild.
B: PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Meets diagnostic criteria for autism

--Prior/Concurrent Therapy--

Other:

* At least 3 months since prior electroconvulsive therapy
* At least 1 month since prior investigational drugs or treatment with any drug known to cause major organ toxicity
* At least 2 weeks since prior monoamine oxidase inhibitors
* At least 6 weeks since prior long acting phenothiazines
* At least 1 week since prior other psychotropic drugs
* No prior fluoxetine of 20 mg/day for 6 weeks
* At least 6 weeks since prior fluoxetine
* No concurrent use of terfenadine (Seldane) or astemizole (Hismanal)
* No concurrent electroconvulsive therapy or other psychotropic drugs (unless otherwise permitted)
* Prior participation in another serotonin reuptake inhibitor trial allowed

--Patient Characteristics--

Hematopoietic: No significant hematopoietic disease

Hepatic: No prior or concurrent liver disease

Renal: No prior or concurrent kidney disease

Cardiovascular:

* No significant cardiovascular disease
* No abnormal EKG

Neurological:

* No prior seizure disorder or high risk development of seizures
* No prior cerebrovascular disease
* No prior brain trauma

Other:

* Not pregnant or nursing
* Negative pregnancy test
* No unstable major medical illness or systemic disease
* No moderate or severe mental retardation and motor deficits (IQ less than 50)
* No family history of bipolar disorder
* No prior or concurrent other mental disorders (e.g., schizophrenia, schizoaffective, organic, or bipolar disorders)
* No significant autoaggressive behavior or serious suicidal risk
* No prior or concurrent gastrointestinal conditions
* No unstable endocrine disease (e.g., hypo or hyperthyroidism)
* No prior or concurrent malignancy
* Must be able to tolerate tapering of psychoactive medication
* No history of hypersensitivity or severe side effects to fluoxetine or other serotonin reuptake inhibitors
* No history of severe personality disorder or noncompliance
C: Inclusion Criteria:

* DSM-IV diagnosis of Autistic Disorder (299.00)
* ABC-I Subscale score of greater than or equal to 18
* CGI-S of greater than or equal to 4
* mental age \>18 months, body weight of at least 20 kg, seizure-free for at least 6 consecutive months and if on anticonvulsants must be on a dosage that has been stable for at least 4 weeks
* Medication free for 1 week before the start of the study for all psychotropic drugs, except 4 weeks for fluoxetine and at least 8 weeks for injectable medications
* Female patients must be premenarchal or sexually abstinent or, if heterosexually active, must practice an effective method of birth control.

Exclusion Criteria:

* History of prior or current DSM-IV psychotic disorder (e.g., schizophrenia, bipolar disorder, other psychosis), Pervasive Developmental Disorder not otherwise specified (PDD NOS), Asperger's, or Rett's
* Any history of hypersensitivity to risperidone, or its excipients in formulation, or other known drug allergy
* Patients who received risperidone within 3 months before screening (except p.r.n. use)
* Patients who did not demonstrate sufficient clinical response to an adequate trial of risperidone treatment in the past (an adequate trial is defined as a period of at least 4 weeks at an adequate dose)
* Neurologic disorder (e.g., Neuroleptic Malignant Syndrome, seizure disorders that are unstable, seizure activity within the past 6 months)
* History of alcohol or substance dependence within 3 months of screening
* Female subject who is pregnant (positive beta-HCG) or breast feeding
* Patients with existing moderate or severe EPS or history of tardive dyskinesia
* Patients who have received an experimental drug or used an experimental medical device within 3 months before the planned start of treatment.
D: Inclusion Criteria:

* Clinical diagnosis of Autism Spectrum Disorder, Asperger Syndrome or Autism
* Male
* Age between 18 and 40 years old

Exclusion Criteria:

* Associated neuro(psycho)logical disorder (i.e. epilepsy, concussion, stroke)
* Eye sight worse than + or - 7
* Genetic syndrome
* Color blindness
* Any contraindication to neuroimaging research as assessed with the MRI screening list:

MRI contraindications:

pacemaker, implanted defibrillator, ear implant / a cochlear implant, insulin or implanted pump, a neurostimulator or VP shunt, any metallic object in the eyes (metallic fragments)

Answer: C