Alpha-2 Agonists. Antipsychotics

Transcription

1 Table 5: Randomized Controlled Trials of Psychotropic Medications in Children and Adolescents with ASD Agent Study Target Symptoms Dose Demographics Significant Side Clonidine Guanfacine Jaselskis et al., Hyperactivity,, , Stereotypy Alpha-2 Agonists mg divided TID Handen, Hyperactivity, Inattention 1-3 mg et al., divided TID 8 children 5-13 yo 7 children with ASD, 5-9 yo Hypotension, drowsiness Drowsiness, irritability Statistically and clinically relevant decrease in ABC subscale. 45% with a >50% decrease in ABC Hyperactivity subscale Antipsychotics Aripiprazole Haloperidol ** Marcus, et al.,, Hyperactivity, ** Owen, et al.,, Hyperactivity, Anderson, et al., Multiple behavioral symptoms, Global functioning Anderson, et al., Multiple behavioral symptoms, Global functioning 5, 10 or 15 mg per, fixed dose 5-15 mg per, flexibly dosed mg per mg per 218 children 98 children 2 7 yo 45 children 2-7 yo Somnolence, weight gain, drooling, tremor, fatigue, vomiting Somnolence, weight gain, drooling, tremor, fatigue, vomiting Sedation, irritability, extrapyramidal symptoms (>25%) Sedation, extrapyramidal symptoms 56% positive response* for 5 mg aripiprazole vs. 35% on placebo Significant improvement in, Hyperactivity and Stereotypy subscales. 52% positive response* for aripiprazole vs. 14% on placebo. Significant improvement in, Hyperactivity & Stereotypy subscales. Behavioral symptoms improved with significant decrease in 8 of 14 items of the CPRS (Children s Psychiatric Rating Scale). Behavioral symptoms improved with significant decrease in 7 of 14 items of the CPRS. Olanzapine ** Hollander, et al., Global functioning, Aggression,Compulsions, mg per 11 children 6-14 yo Weight gain, sedation 50% of those on olanzapine much or very much improved in global functioning vs. 20% on placebo Risperidone RUPP, , Hyperactivity, mg per 101 children Weight gain, increased appetite, fatigue, 69% had a positive response* on risperidone vs. 12% positive 36

2 , drowsiness, drooling, dizziness Risperidone vs. Haloperidol Valproic Acid Lamotrigine Levitiracetam ** Shea, et al.,, Hyperactivity, McDougle, et al., Social and communication impairment, Repetitive behavior & Stereotypy ** Miral, et al., Behavior, Social, Sensory, Language mg/kg/ mg per mg/kg/ Mood Stabilizers Hellings, et al., 20 mg/kg/ avg level ** Hollander, et Repetitive Behavior mg al., per Hollander, et al., Global irritability Dosed to a mean level of 89.8 mcg per ml ** Belsito, et al.,, Social behavior ** Wasserman, et al., Global functioning 5 mg per kg per mg per kg/ 79 children 5-12 yo 101 children 30 children 8-18 yo 30 subjects 6-20 yo 12 children, and 1 adult, 40 yo 27 children 28 children 3-11 yo 20 children Norepinephrine Reuptake Inhibitors Weight gain, somnolence, Weight gain, increased appetite, fatigue, drowsiness, drooling, dizziness EPS, weight gain. gynecomastia Increased appetite, skin rash, aggression Skin rash, irritability Insomnia, Aggression response* on placebo. Significant positive findings for and stereotypy 64% improvement in ABC on risperidone vs. 31% improvement on placebo. Significant positive finding for Significant response*** for repetitive behavior and stereotypy on risperidone Risperidone reported superior to haloperidol only on ABC Total score, no sub-scales reported. No significant difference for ABC sub-scale Statistically significant decrease in repetitive behavior on C- YBOCS 62.5% positive response for irritability on the CGI on divalproex vs. 9.09% on placebo. irritability or social behavior on multiple instruments. global functioning or irritability 37

3 Atomoxetine HCI **Harfterkamp, M, Hyperactivity 1.2 mg/kg/ 97 children Nausea, anorexia et al., Inattention Fatigue, early wakening Citalopram Fluoxetine Clomipramine Methylphenidate ** Arnold, et al., Hyperactivity Inattention mg divided bid mean 44mg/ 16 children 5-15 yo Serotonin Reuptake Inhibitors King, et al., Repetitive behavior mg per (mean 16 mg /) Hollander, et al., Repetitive behavior mg/ (mean 9.9 mg/) Gordon, et.al., Stereotypy, Repetitive behavior, Compulsions Remington et al., Stereotypy,, Hyperactivity mg / (mean 152) mg per (mean mg/) Stimulants RUPP, Hyperactivity mg per , divided tid Pearson, et al., Hyperactivity Inattention mg qam, methylphenidate extended release Handen, et al., Hyperactivity mg/kg/dose, bid-tid 149 children 39 children 12 children 6-18 yo 31 subjects less than 20 yo 58 children 5-14 yo 24 children 7-12 yo 13 children 5-11 yo Upper G.I. symptoms, fatigue, racing heart Hyperactivity, insomnia, inattention, impulsivity, diarrhea, stereotypy None significant Insomnia, constipation, twitching, tremors Lethargy, tremors, tachycardia, insomnia, diaphoresis, nausea Decreased appetite, insomnia, irritability,emotionality Decreased appetite, insomnia Social, irritability Significant difference in the ADHD-RS for active treatment group. No difference in CGI-I 57% positive response* for parent-rated ABC Hyperactivity subscale vs. 25% on placebo. repetitive behavior on CGI-I and CY-BOCS PDD Statistically significant decrease in repetitive behavior on CY- BOCS compulsions scale Decrease in repetitive behavior on CPRS stereotypy, irritability, or for clomipramine on the ABC. 49% positive responders* for vs. 15.5% on placebo Significant decrease in & inattention on multiple teacher & parent measures 8 of 13 children with a >50% decrease in on the Teacher Conners Hyperactivity 38

4 Quintana, et al., Hyperactivity mg bid 10 children, anorexia, yo insomnia Decrease in ABC Hyperactivity subscale by 8 points > placebo Miscellaneous Amantadine Cyproheptadine (in combination with haloperidol) Donepezil Naltrexone ** King, et al., Hyperactivity, mg per kg per Akhondzadeh, et al., ABC Total Score CARS Chez, et al., Autistic Behavior Expressive-Receptive Communication Willemsen- Swinkels, et al., Social Behavior ** Kolmen, et al., Hyperactivity Communication initiation Titrated up to 0.2 mg/kg per mg per Single 40 mg dose 1 mg per/kg per 39 children 5-19 yo 3-11 yo 43 children 2-10 yo 20 children 3-7 yo 13 children Insomnia None significant, trend toward increased appetite Diarrhea, stomach cramping, irritability Sedation, Increased stereotypy Transient sedation No statistical difference in parent ABC Hyperactivity or sub scales, statistical improvement in clinician Hyperactivity and Inappropriate Speech subscales. Statistically significant difference in ABC Total score and CARS diagnostic screening tool, with unknown clinical significance. Autistic behavior statistically, improved on CARS diagnostic screening tool with unknown clinical significance. No effect on social behavior Significant reduction in ABC compared to placebo. communication initiation ** Feldman, et al., Communication 1 mg/kg per 24 children, Campbell, et al., CGI CPRS Discriminant learning Hyperactivity Campbell, et al., Hyperactivity Discriminant learning Self-injurious behavior mg/kg per mg/kg per 18 children 41 children Transient sedation Increased aggression and stereotypy None significant multiple communication measures. the CGI or CPRS or discriminant learning. Positive trend for Significantly reduced ; no effect on discriminant learning. Positive 39

5 Pentoxifylline (in combination with risperidone) Akhondzadeh, et al., , Hyperactivity, mg per 4-12 yo Sedation, GI effects, increased appetite trend for self-injurious behavior Significant improvement on the ABC and Social Withdrawal subscales * A positive response in this study was defined as a >25% reduction in the ABC subscale and a Much Improved or Very Much Improved rating on the CGI-I. ** Study identified as funded by pharmaceutical industry. *** A positive response in this study was defined as a >25% reduction in the C-YBOCS compulsions score and a Much Improved or Very Much Improved rating on the CGI-I. 40