Use of psychotropic medication in children and adolescents with autism spectrum disorders.

OBJECTIVES: The goal of this study was to examine rates of psychotropic medication use and identify associated child and family characteristics among children and adolescents with autism spectrum disorder (ASD) enrolled in an autism registry maintained by the Autism Treatment Network (ATN). METHODS: The sample, derived from the ATN registry, consists of 2853 children aged 2 to 17 years with diagnoses of ASD supported by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the Autism Diagnostic Observation Schedule with available data on medication use. As part of initial enrollment in the registry, parents completed questionnaires on current psychotropic medication use, psychiatric and medical conditions, and demographics. RESULTS: Of the 2853 children, 763 (27%) were taking ≥ 1 psychotropic medication; 15% were prescribed 1 medication, 7.4% received 2 medications, and 4.5% received ≥ 3. Among children aged 3 to 5 years, 11% were taking ≥ 1 psychotropic medication; among 6- to 11-year-old children, 46%; and 66% of adolescents aged 12 to 17 years were taking at ≥ 1 psychotropic medication. A parent report of comorbid diagnosis of attention-deficit/hyperactivity disorder, bipolar disorder, obsessive-compulsive disorder, depression, or anxiety was associated with a high rate of use, with 80% receiving ≥ 1 psychotropic medication. Only 15% of children with no comorbid psychiatric disorder were taking psychotropic medication. Psychotropic medication use was also related to sleep and gastrointestinal problems. CONCLUSIONS: The prescription of psychotropic medications in this registry sample is highly related to comorbid psychiatric disorder. Other factors associated with use include medical comorbidities, race, ethnicity, and older age.

Validation of a care and comfort hypertonicity questionnaire.

The lack of evidence regarding functional and quality of life benefits resulting from tone reduction with intrathecal baclofen (ITB) infusion treatment relates to the lack of validated and responsive measures. We integrated our scale/questionnaire, developed from chart review, with the non-validated Caregiver Questionnaire (CQ) to yield a final document, the Care and Comfort Hypertonicity Questionnaire (CCHQ). Convergent validity was achieved by administering the CCHQ to 47 patients with spastic/dystonic cerebral palsy (CP) who were being evaluated for tone management. The population studied included 18 females and 29 males (mean age 10y [SD 4y 10mo]; range 3y 1mo-21y 1mo). Twenty-five patients were subsequently referred for botulinum toxin (BTX-A) injections (mean Gross Motor Function Classification System [GMFCS] 3.2); 11 patients were referred for ITB (mean GMFCS 4.4); four were referred for orthopedic surgery (mean GMFCS 3.3); 3 were referred for selective dorsal rhizotomy (mean GMFCS 2.7); one was recommended for oral baclofen (GMFCS 5); and three were recommended for no treatment (mean GMFCS 3.7). Blinded to the score, those with the highest scores (severe hypertonicity) were recommended for ITB; those with the lowest scores were recommended for BTX-A injections. Responsiveness of the CCHQ was established by administering the questionnaire to patients who already had an implanted ITB pump. The children with the largest dose increase demonstrated a statistically significant improvement in the CCHQ score. This scale can be used to document the efficacy of treating severe hypertonicity both in clinical and research protocols.

Rapid dose escalation with quetiapine: a pilot study.

The original dosing recommendations for quetiapine in the treatment of schizophrenia suggested escalation to 400 mg/d using the following schedule, administered twice daily in divided doses: Day 1, 50 mg; Day 2, 100 mg; Day 3, 200 mg; Day 4, 300 mg; Day 5, 400 mg. In practice, however, clinicians often exceed these recommendations because of the need to obtain a therapeutic response in patients with psychosis as quickly as possible. This study was designed to determine a faster tolerable dosage-escalation schedule for quetiapine in acutely ill, hospitalized patients with schizophrenia. In this multicenter, placebo-controlled, double-blind pilot study, adult patients were randomly assigned to escalation schedules that would achieve a target dosage of 400 mg/d in either 5, 3, or 2 days. Safety and tolerability were assessed by interviews, physical examinations and vital signs, laboratory tests, and electrocardiograms. The enrolled population consisted of 69 patients who were randomized to 1 of the 3 dose-escalation schedules. Treatment-related adverse events were few among the 67 evaluable patients, with most rated as mild in intensity. Among 69 enrolled patients, only 3 withdrew because of an adverse event (agitation). Objective assessments and adverse events were similar between the 3 groups. In this study of patients with acute schizophrenia, quetiapine dosage was increased to 400 mg/d in 5, 3, and 2 days with similar safety and tolerability, suggesting that escalation to therapeutically effective dosages can be accomplished in less than 5 days.

A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression.

OBJECTIVE: There is a major unmet need for effective options in the treatment of bipolar depression. METHOD: Five hundred forty-two outpatients with bipolar I (N=360) or II (N=182) disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 8 weeks of quetiapine (600 or 300 mg/day) or placebo. The primary efficacy measure was mean change from baseline to week 8 in the Montgomery-Asberg Depression Rating Scale total score. Additional efficacy assessments included the Hamilton Depression Rating Scale, Clinical Global Impression of severity and improvement, Hamilton Anxiety Rating Scale, Pittsburgh Sleep Quality Index, and Quality of Life Enjoyment and Satisfaction Questionnaire. RESULTS: Quetiapine at either dose demonstrated statistically significant improvement in Montgomery-Asberg Depression Rating Scale total scores compared with placebo from week 1 onward. The proportions of patients meeting response criteria (> or =50% Montgomery-Asberg Depression Rating Scale score improvement) at the final assessment in the groups taking 600 and 300 mg/day of quetiapine were 58.2% and 57.6%, respectively, versus 36.1% for placebo. The proportions of patients meeting remission criteria (Montgomery-Asberg Depression Rating Scale < or =12) were 52.9% in the groups taking 600 and 300 mg/day of quetiapine versus 28.4% for placebo. Quetiapine at 600 and 300 mg/day significantly improved 9 of 10 and 8 of 10 Montgomery-Asberg Depression Rating Scale items, respectively, compared to placebo, including the core symptoms of depression. Treatment-emergent mania rates were low and similar for the quetiapine and placebo groups (3.2% and 3.9%, respectively). CONCLUSIONS: Quetiapine monotherapy is efficacious and well tolerated for the treatment of bipolar depression.