Overdoses and ingestions of second-generation antipsychotics in children and adolescents.

OBJECTIVE: We reviewed the available published data on intentional or unintentional secondgeneration antipsychotic overdoses in children and adolescents. The prescribing of secondgeneration antipsychotics has continued to increase over the past decade for children, adolescents, and adults. The authors reviewed the existing literature to determine the circumstances, presenting problems, treatment, and outcomes of youths who were exposed to nontherapeutic doses of these medications. METHODS: A systematic English-language Medline search of all reports (1989-2005) and a review of the bibliographies of all articles obtained was done to identify papers reporting an overdose or ingestion of a second-generation antipsychotic. Data were reviewed on clozapine, risperidone, olanzapine, ziprasidone, quetiapine, and aripiprazole. The annual reports of the American Association of Poison Control Centers National Data Collection System were reviewed from 1990 to 2003, the most recent report currently available. All fatalities in children and youths under 18 years of age were included. RESULTS: The literature review identified 40 reports that included 63 patients, ranging in age from 1 day to 17 years of age. The clinical presentations included drowsiness, lethargy, agitation, irritability, combativeness, and tachycardia. There were 11 fatalities in the cases reviewed, 1 from clozapine overdose, 3 from risperidone overdose, 2 from olanzapine overdose, and 5 from quetiapine overdose. All other cases reported no significant sequelae and resolved without any reported clinical consequences. Duration of overdose symptoms ranged from 24 hours to 7 days. One case of clozapine intoxication showed resolution of symptoms in 6 hours and, in another case of olanzapine overdose, symptoms resolved in 13 days. The most frequently employed treatments included intubation, gastric lavage, activated charcoal, intravenous fluids, artificial respiration, and restraints or sedatives. CONCLUSIONS: There is a need for future case reports to include serum medication level, weight of patient, coingestants, the health of the patient at baseline, relevant laboratory and toxicology studies and a standardized scale to rate the level of consciousness, such as the Glasgow Coma Scale. The existing pharmacovigilance data reports indicate these medications are relatively safe when taken in overdose, particularly when coingestants are not involved.

The social anxiety spectrum.

Social anxiety disorder is well suited to the spectrum concept because it has trait-like qualities of early onset, chronicity, and no empirically derived threshold that demarcates normal from clinically significant trait social anxiety. Social anxiety disorder has been shown to respond to relatively specific pharmacologic and cognitive-behavioral therapies, which makes identification of other conditions that may lie on the social anxiety disorder spectrum important because of possible treatment implications. Biologic markers associated with social anxiety disorder also may be shared by similar but nonidentical traits, such as behavioral inhibition and detachment. Clarification of the trait spectrums associated with specific biologic systems offers an opportunity for improving the understanding of the origin of these conditions. Strong evidence exists that at least some forms of shyness, avoidant personality disorder, and selective mutism lie on a social anxiety disorder spectrum. For several other disorders that share a prominent focus on social comparison, significant subgroups of patients seem to have features of social anxiety disorder. These disorders include major depression (especially the atypical subtype), body dysmorphic disorder, and eating disorders. Several other disorders marked by social dysfunction or inhibition, including substance use disorders (especially alcoholism), paranoid disorder, bipolar disorder, autism, and Asperger's disorder, also may show some overlap with social anxiety disorder features (e.g., social anxiety as a cause or complication of substance abuse, social avoidance in paranoid disorder, social disinhibiton in bipolar disorder, and social communication deficits in autism and Asperger's disorder). Social anxiety disorder also is associated with other anxiety disorders in general and other phobias in particular. In respect to traits, a growing body of evidence links behavioral inhibition to the unfamiliar to a social anxiety disorder spectrum with some specificity. Biologic measures of dopamine system hypoactivity have been linked to social anxiety disorder, trait detachment, and general deficits in reward and incentive function. It remains to be clarified, however, whether this brain system function is best characterized by a social anxiety disorder spectrum or some variant that incorporates social reward deficits or social avoidance behavior. Social anxiety disorder, shyness, and behavioral inhibition all seem to have a genetic component, but more research is needed to attempt to identify a more specifically heritable temperament associated with these conditions. Finally, the emergent concept of a social anxiety spectrum needs maturation. Although the notion of a single social anxiety disorder spectrum currently has some clinical use, the authors believe that exclusive focus on the notion of a single continuum with two extremes--from social disinhibition in mania to the most severe form of social anxiety, avoidant personality disorder--is premature and limiting in respect to etiologic research. An alternative approach is to conceptualize multiple, probably overlapping spectra in this area of social psychopathology. Individual dimensions might be based on various core phenomenologic, cognitive, or biologic characteristics. A bottom-up biologic approach holds promise for identifying spectra with a common etiology that might respond to specific treatments. Taking a pluralistic view of the concept of spectrum at this stage may help accelerate our understanding of social anxiety and related disorders.

Pharmacotherapy of social anxiety disorder.

Over the last few years, a number of medications have demonstrated their efficacy in the acute treatment of social anxiety disorder. At present, selective serotonin reuptake inhibitors probably constitute the first line treatment, based on their safety, tolerability, and efficacy in the treatment of social anxiety disorder and common comorbid conditions. Data from single trials suggest that clonazepam, bromazepam, and gabapentin may have efficacy similar to the serotonin reuptake inhibitors, but further studies are needed to confirm these findings. The monoamine oxidase inhibitor phenelzine appears to be at least as efficacious as these other agents, but should be reserved for cases that fail to respond to these safer medications. Among the reversible inhibitors of monoamine oxidase A, brofaromine may also be an effective drug, while moclobemide appears to be less potent. Future research directions should include delineating ways to achieve remission (as opposed to response); developing strategies for augmenting partial responders and treating nonresponders to first line approaches; studying the long-term response to medication and prevention of relapse when medication is discontinued; clarifying ways to integrate psychosocial and pharmacological treatment approaches; developing predictors of which patients do best with which treatments; and the treatment of social anxiety disorder in children and adolescents.