Paliperidone for irritability in adolescents and young adults with autistic disorder
ABSTRACT Individuals with autistic disorder (autism) frequently exhibit significant irritability marked by severe tantrums, aggression, and self-injury. Despite advances in the treatment of this symptom domain in autism, there remains an ongoing need for more effective and better tolerated pharmacotherapies.
The aim of this study is to determine the effectiveness and tolerability of paliperidone for irritability in autism.
This is a prospective, 8-week open-label study of paliperidone in 25 adolescents and young adults with autism. Primary outcome measures included the Clinical Global Impressions-Improvement (CGI-I) Scale and the Irritability subscale of the Aberrant Behavior Checklist (ABC-I). Concomitant medications (except antipsychotics) were permitted if dosages were stable for ≥2 months.
Twenty-one (84 %) of 25 subjects ages 12-21 years (mean 15.3 years) responded to paliperidone, based on a CGI-I Scale score of 1 or 2 (very much or much improved) and ≥25 % improvement on the ABC-I. The mean final dosage of paliperidone was 7.1 mg/day (range 3-12 mg/day). Two subjects discontinued paliperidone prior to study completion (moderate sedation, n = 1; nonresponse, n = 1). Mild-to-moderate extrapyramidal symptoms were recorded in four subjects. A mean weight gain of 2.2 ± 2.6 kg (range -3.6 to +7.9 kg) was recorded. Mean age- and sex-normed body mass index increased from 23.6 to 24.2 (p ≤ 0.001). Mean serum prolactin increased from 5.3 to 41.4 ng/mL (p ≤ 0.0001).
Paliperidone treatment was associated with significant improvement in irritability and was generally well tolerated. Larger scale, placebo-controlled studies are needed to elucidate the efficacy and tolerability of paliperidone in this population.
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ABSTRACT: Objective To evaluate the effect of antipsychotics on the corrected QT (QTc) interval in youth. Method We searched PubMed (http://www.ncbi.nlm.nih.gov/pubmed) for randomized or open clinical trials of antipsychotics in youth <18 years with QTc data, meta-analyzing the results. Meta-regression analyses evaluated the effect of age, sex, dose, and study duration on QTc. Incidence of study-defined QTc prolongation (>440-470 milliseconds), QTc >500 milliseconds and QTc change >60 milliseconds were also evaluated. Results 55 studies were meta-analyzed, evaluating 108 treatment arms covering 9 antipsychotics and including 5,423 patients with QTc data (age=12.8±3.6 years, female=32.1%). Treatments included aripiprazole: studies=14; n=814; haloperidol: studies=1; n=15; molindone: studies=3; n=125; olanzapine: studies=5; n=212; paliperidone: studies=3; n=177; pimozide: studies=1; n=25; quetiapine: studies=5; n=336; risperidone: studies=23; n=2,234; ziprasidone: studies=10, n=523; and placebo: studies=19, n=962. Within group, from baseline to endpoint, aripiprazole significantly decreased the QTc interval (-1.44 milliseconds, CI: -2.63 to -0.26, p=.017), while risperidone (+1.68, CI: +0.67 to +2.70, p=.001) and especially ziprasidone (+8.74, CI: +5.19 to +12.30, p<.001) significantly increased QTc. Compared to pooled placebo arms, aripiprazole decreased QTc (p=.007), while ziprasidone increased QTc (p<.001). Compared to placebo, none of the investigated antipsychotics caused a significant increase in the incidence of the 3 studied QTc prolongation measures, but there was significant reporting bias. Conclusion Based on these data, the risk of pathological QTc prolongation seems low during treatment with the 9 studied antipsychotics in otherwise healthy youth. Nevertheless, since individual risk factors interact with medication-related QTc effects, both medication and patient factors need to be considered when making antipsychotic choices.Journal of the American Academy of Child & Adolescent Psychiatry 01/2015; 54(1):25-36. DOI:10.1016/j.jaac.2014.10.002 · 6.35 Impact Factor
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ABSTRACT: Although there is no known efficacious pharmacotherapy for core symptoms of autism spectrum disorder (ASD), psychotropic medications are commonly prescribed for behavioral/emotional symptoms associated with ASD. We reviewed current evidence-based pharmacotherapy options and updates from recent noteworthy studies. Atypical antipsychotics, particularly risperidone and aripiprazole, are effective in reducing irritability, stereotypy and hyperactivity. Metabolic adverse events, including weight gain and dyslipidemia, are common. Methylphenidate is effective in reducing attention-deficit hyperactivity disorder (ADHD) symptoms. Atomoxetine and alpha-2 agonists appear effective in reducing ADHD symptoms. Selective serotonin reuptake inhibitors are not effective in improving repetitive behaviors in children with ASD, and frequently cause activating adverse events. Efficacy of antiepileptic drugs is inconclusive. Overall, efficacy and tolerability of pharmacotherapy in children with ASD are less favorable than data seen in typically developing children with similar symptoms. Newer agents, including glutamatergic agents and oxytocin, appear promising albeit with mixed results. Current evidence-based pharmacotherapy options in children with ASD are very limited, and many have substantial adverse events. Clinicians should use pharmacotherapy as a part of comprehensive treatment, and judiciously weigh risks and benefits. New pharmacotherapy options for core symptoms as well as co-occurring symptoms of ASD are in urgent need.
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ABSTRACT: The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse effects. Pregnenolone yielded a statistically significant improvement in the primary measure, Aberrant Behavior Checklist (ABC)-Irritability [from 17.4 ± 7.4 at baseline to 11.2 ± 7.0 at 12 weeks (p = 0.028)]. Secondary measures were not statistically significant with the exception of ABC-lethargy (p = 0.046) and total Short Sensory Profile score (p = 0.009). No significant vital sign changes occurred during this study. Pregnenolone was not associated with any severe side effects. Single episodes of tiredness, diarrhea and depressive affect that could be related to pregnenolone were reported. Overall, pregnenolone was modestly effective and well-tolerated in individuals with ASD.Journal of Autism and Developmental Disorders 05/2014; 44(11). DOI:10.1007/s10803-014-2144-4 · 3.34 Impact Factor