Psychopharmacological interventions in autism spectrum disorder.

INTRODUCTION: Individuals with autism spectrum disorder (ASD) commonly present for treatment of emotional and behavioral disturbances associated with ASD's "core" symptoms. Psychotropic medications are widely utilized in alleviating associated emotional and behavioral symptoms. AREAS COVERED: Emotional and behavioral disturbances associated with ASD include irritability/severely disruptive behavior, which comprises the heaviest symptom burden; hyperactivity and other Attention-Deficit-Hyperactivity-Disorder (ADHD)-type symptoms; repetitive/stereotyped behaviors; and social withdrawal. Existing evidence for medications for each of these symptom clusters will be examined in this review. EXPERT OPINION: Psychopharmacological treatment of core and associated symptoms in ASD is challenging, in large part because of the heterogeneity in the presentation of ASD. Furthermore, children and adolescents with ASD are more vulnerable to the side effects of psychopharmacological intervention than their age-matched, typically developing counterparts. Currently, risperidone and aripiprazole are the only medications that have been (relatively) reliably shown to help treat certain symptom clusters associated with ASD, namely severely disruptive behavior and hyperactivity. Recent studies have begun to look at medications with mechanisms that are novel in the treatment of ASD and that may address underlying pathophysiology and/or core symptoms such as glutamate-modulating agents. Overall, randomized, placebo-controlled studies of medications for the treatment of ASD are scarce.

Low rates of depressed mood and depression diagnoses in a clinic review of children and adolescents with autistic disorder.

OBJECTIVES: The purpose of this study was to investigate the prevalence of depression diagnoses and related clinical data in an outpatient sample of youth with autistic disorder. METHODS: Records of 123 psychiatrically referred children and adolescents with a Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of autistic disorder were examined. Mood disorder diagnoses and chief complaints along with family mood disorder history were the primary variables analyzed. RESULTS: Four subjects (3%) presented with depressed mood. Irritability complaints were frequent (n=78, 63%). Six subjects (5%) received a mood disorder diagnosis; all with mood disorder, not otherwise specified. No subjects received a depressive disorder diagnosis. Family history of mood disorders was common. CONCLUSIONS: Findings raise questions about the appropriate characterization and potential misdiagnoses of depression in youth with autistic disorder.

Psychopharmacological interventions in autism spectrum disorder.

After participating in this educational activity, the physician should be better able to1. Prescribe the appropriate psychotropic medication to treat symptoms of ASD.2. Identify the side effects of the psychotropic medications used to treat ASD.Autism spectrum disorders (ASDs) are characterized by core deficits in social communication and language, and restrictive and repetitive behaviors that cause significant functional impairment and distress for affected individuals and their caregivers. The increasing prevalence of ASD, most recently estimated as 1 in 88 children, presents an ever-increasing burden on families, schools, medical systems, and society at large. Individuals with ASD commonly present for treatment of associated emotional and behavioral disturbances that include anxiety, symptoms of ADHD, compulsions and other repetitive behaviors, mood lability, irritability, aggression, and sleep disturbance. Psychotropic medications are widely utilized in alleviating these symptoms, though rigorous clinical trials in ASD are lacking for most areas of impairment. Strong evidence from randomized, placebo-controlled trials supports the use of atypical antipsychotics, particularly risperidone and aripiprazole, for managing severe irritability and aggression in ASD. Serotonin reuptake inhibitors are commonly used to treat anxiety and compulsions, though reports of efficacy in the literature are mixed, and behavioral side effects in children are common. Minimal evidence supports the utility of anticonvulsants and traditional mood stabilizers in managing mood lability and aggression. Stimulant and nonstimulant ADHD medications can be effective for reducing hyperactivity, inattention, and impulsivity, though to a lesser degree than in ADHD populations without ASD and with greater risk of adverse effects. Psychopharmacological interventions in development for core symptoms of autism include those that target the glutamatergic and GABAergic neurotransmitter systems and the neuropeptide oxytocin. Further research is needed to establish evidence-based interventions in ASD populations.

Retrial of selective serotonin reuptake inhibitors in children with pervasive developmental disorders: a retrospective chart review.

BACKGROUND: Youths with pervasive developmental disorders (PDDs) often have symptoms that fail to respond to selective serotonin reuptake inhibitor (SSRI) treatment. These children may be given a subsequent trial of another SSRI. This study reports on the outcome of PDD youths who received a second SSRI trial after an initial treatment failure. METHODS: Clinic charts were reviewed for 22 outpatient youths with a DSM-IV diagnosis of a PDD who were treated with an SSRI after an initial failure with a previous SSRI. Response for the second SSRI trial was determined using the Clinical Global Impressions-Improvement Scale (CGI-I). Treatment indications, symptom severity, demographic data, and side effects were recorded. RESULTS: For the second SSRI trial, 31.8% of the subjects were rated as much improved on the CGI-I scale and determined to be responders, with 68.2% of the subjects demonstrating activation side effects. 90% of subjects demonstrated activation side effects when data from both SSRI trials were combined. There were no statistically significant associations between outcome of the second SSRI trial and clinical/demographic variables. CONCLUSIONS: A second trial of an SSRI after an initial SSRI treatment failure was often unsuccessful in children and adolescents with PDDs. Activation side effects were common. Because alternative treatments in this population are limited, a second trial of an SSRI may still be considered. The study was limited by its retrospective design and by its small sample size.

Limit setting and projective identification in work with a provocative child and his parents: a revisiting of Winnicott's "Hate in the Countertransference.

Dealing with children who have disruptive behavior disorders can evoke feelings of frustration and anger in their therapists. D.W. Winnicott discussed the complexities in the treatment of enraging patients in his article "Hate in the Countertransference" (1949). In the following paper, I will depict the relationship between limit setting, projective identification dynamics, and enraging behavior in the treatment of a provocative latency-aged boy. I will argue that poor limit setting caused by powerful projective identification dynamics were central to the pathology of the boy and his family. These dynamics partially repeated in the boy's treatment--an outcome of which Winnicott had warned. The repetition contributed to the boy becoming physically out of control in my office and led to a disruption in his treatment. The establishment of solid limits by addressing projective identification forces was necessary for the improvement in the disruptive behavior of the child.

Treatment outcome and outcome associations in children with pervasive developmental disorders treated with selective serotonin reuptake inhibitors: a chart review.

PURPOSE: The aim of this study was to determine the outcome and predictors of outcome with selective serotonin reuptake inhibitors (SSRIs) in outpatient children and adolescents with pervasive developmental disorders (PDDs). METHOD: Clinic charts were reviewed for 89 outpatient youths with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of a PDD who were treated with SSRIs. Response was determined using the Clinical Global Impressions (CGI) scale. Side-effect and demographic data, including family history, were recorded. RESULTS: Forty-four point nine percent (44.9%) were determined to be much improved and considered responders. Fifty-four percent (54%) of the subjects demonstrated activation side effects. In 35.4% of these subjects, the activation side effects led to drug discontinuation. Pearson chi-squared and regression analysis demonstrated an association between SSRI response and a family history of PDD. There were no significant associations between clinical variables and activation side effects. CONCLUSIONS: SSRI treatment led to modest response rate in this group of youths with PDDs. Activation side effects were frequent, often leading to treatment dropouts. Potential outcome associations include a family history of PDDs.

Long-term outcome with divalproex in children and adolescents with bipolar disorder.

OBJECTIVE: To assess the outcome and safety of divalproex treatment in children and adolescents with bipolar disorder. METHODS: We conducted a chart review of children and adolescents who were treated with divalproex and who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for bipolar disorder (dose 966 +/- 501 mg/day, level 79.4 +/- 23.1 micro g/mL, duration 1.4 +/- 1.5 years). Responders were defined as those showing moderate to marked response on the Clinical Global Impression-Improvement (CGI-I) scale. RESULTS: Eight of 15 (53%) patients responded to divalproex treatment for mixed episode (n = 6), disruptive behavior (n = 4), pure mania (n = 3), or depression (n = 2). Six of 15 (40%) discontinued divalproex, most due to side effects (n = 5). The most common side effect was weight gain (4/15, 27%). CONCLUSION: In children aged 4-18 years, divalproex treatment was related to improved outcome in the long-term treatment of bipolar disorder. One third of the patients discontinued treatment secondary to side effects, including a case of reversible liver enzyme elevation.