Second-Generation Antipsychotic Medications in Children and Adolescents

Department of Psychiatry, University of Washington School of Medicine, Seattle, WA, USA.
Journal of Child and Adolescent Psychopharmacology (Impact Factor: 2.93). 02/2004; 14(3):372-94. DOI: 10.1089/cap.2004.14.372
Source: PubMed


We reviewed available pediatric literature on second-generation antipsychotic medications to assess current evidence of efficacy and safety.
An English language MEDLINE search (1974-2003) was conducted using key words-atypical antipsychotics, children and adolescents, toxicity, clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole. Additional efficacy and safety data were obtained from drug manufacturers.
We identified 176 reports, including 15 double-blind, controlled trials, 58 openlabel studies, 18 retrospective chart reviews, and 85 case series/reports. The majority of these studies (43%) were of risperidone. Evidence suggests that second-generation antipsychotics are efficacious in the treatment of psychosis, bipolar disorders, pervasive developmental disorders, and Tourette's Disorder, and are potentially useful in mental retardation, conduct disorder, and severe attention deficit hyperactivity disorder (ADHD). The most frequently reported side effects included cardiovascular effects, weight gain, sedation, sialorrhea, extrapyramidal signs, and hyperprolactinemia, although the relative frequencies of these untoward effects vary among medications.
Although the evidence base for pediatric use of second-generation antipsychotics is expanding, the majority of available studies are anecdotal, or short-term, openlabel trials. Reports suggest that these compounds are effective for a variety of psychiatric disorders in children and adolescents, but additional double-blind, controlled studies are required to establish definitive efficacy. Although these medications appear to be well tolerated in short-term studies, long-term follow-up investigations and ongoing clinical monitoring are necessary to confirm their safety in this age group.

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    • "This makes the brain's ontogenetic trajectory especially vulnerable to environmental influences, including psychotropic drug therapy (review in Andersen and Navalta, 2011). AAPDs are moderately well tolerated in adult-and pediatric patients in the short term (Kapetanovic and Simpson, 2006; Shekelle et al., 2007; Zuddas et al., 2011), but the long-term sequelae that follow cessation of APD treatment in pediatric patients are unknown (Cheng-Shannon et al., 2004) and are likely to differ from those of adult treatment, due to the numerous differences between the mature and developing brains. This expectation is supported by the fact that when OLA and other atypical AAPDs are chronically or sub-chronically administered to adult humans, the effects of treatment dissipate when the drugs are withdrawn (Sedvall, 1990). "
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    ABSTRACT: Atypical antipsychotic drugs (AAPDs) are widely used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of AAPD treatment before the brain is fully developed. Indeed, we and others have previously reported that treatment of adolescent rats with olanzapine (OLA; a widely prescribed AAPD) on postnatal days 28-49, under dosing conditions that approximate those employed therapeutically in humans, causes long-term behavioral and neurobiological perturbations. We have begun to study the mechanisms of these effects. Dopamine (DA) and serotonin (5HT) regulate many neurodevelopmental processes. Currently approved AAPDs exert their therapeutic effects principally through their DAergic activities, although in schizophrenia (SZ) and some other diseases for which AAPDs are prescribed, DAergic dysfunction is accompanied by abnormalities of glutamatergic (GLUergic) and γ-aminobutyric acidergic (GABAergic) transmission. Here, we use proton magnetic resonance spectroscopy ((1)H MRS) to investigate the effects of adolescent OLA administration on GABA and GLU levels. We found that the treatment caused long-term reductions in the levels of both GLU and GABA in the nucleus accumbens (NAc) of adult rats treated with OLA during adolescence. The NAc is a key node in the brain's "reward" system, whose function is also disrupted in schizophrenia. Further research into potential, OLA-induced changes in the levels of GLU and GABA in the NAc and other brain areas, and the dynamics and mechanisms of those changes, are an essential step for devising new adjunct therapies for existing AAPDs and for designing new drugs that increase therapeutic effects and reduce long-term abnormalities when administered to pediatric patients. Copyright © 2014 Elsevier B.V. All rights reserved.
    Schizophrenia Research 12/2014; 161(2-3). DOI:10.1016/j.schres.2014.10.034 · 3.92 Impact Factor
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    • "One study investigated the effect of risperidone on CD in preschool children in an open-label case series,[22] two study was retrospective,[2324] six articles were not experimental studies,[25262728] one study was post hoc analysis of data reporting the effect of risperidone on affective symptoms in DBDs,[29] three studies followed the efficacy, safety and tolerability of risperidone in patients of an open label study with DBDs,[303132] and two studies were a pooled analysis of risperidone effects in children with low intelligence.[3334] "
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    ABSTRACT: This study evaluates the evidence-based administration of risperidone and paliperidone for the treating children and adolescents with conduct disorder (CD). A review of the current literature from clinical trials that investigated the efficacy of risperidone and paliperidone on CD considering the inclusion criteria and search strategies was performed by a search of PubMed and Google Scholar databases. Out of 53 titles, 31 were irrelevant. The abstract of 22 potentially related articles were studied. Only six articles reported the results of clinical trial. However, one of them reported the effect of risperidone on conduct behaviors in autistic disorders. One study was a re-analysis of two previous studies, one study reported the effects of maintenance versus withdrawal of risperidone treatment and two studies included children with sub-average intelligence. Headache, somnolence and increased appetite are among the most common reported adverse effects. No study examined the effect of paliperidone on CD was found. Current literature suggests that risperidone could be effective for treating some conduct behaviors in children and adolescents. The effect of risperidone on CD is not a well-researched area. There is no well-controlled evidence based reports about the safety and efficacy of risperidone for the treatment of CD. Further trials should examine the efficacy of these medications on CD rather than conduct behaviors or disruptive behavior disorders.
    Journal of research in medical sciences 11/2013; 18(11):998-1003. · 0.65 Impact Factor
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    • "Patients with psychotic illness often require long-term maintenance therapy, but most pediatric APD treatment is for other, off-label indications [12], [13], for which consensus guidelines [14], [15], [16] recommend trial off-medication after stability is achieved. Although short-term tolerance of APDs is reasonably good in adult and pediatric patients [17], the long-term sequelae that follow cessation of APD treatment in pediatric patients are unknown [9]. In the mature brain, dopaminergic (DAergic) signaling is one of the mechanisms of cognition, learning and memory [18], [19]. "
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    ABSTRACT: Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug treatment. Most antipsychotic drugs are potent antagonists or partial agonists of dopamine D2 receptors; atypical antipsychotic drugs also antagonize type 2A serotonin receptors. Dopamine and serotonin regulate many neurodevelopmental processes. Thus, early life antipsychotic drug treatment can, potentially, perturb these processes, causing long-term behavioral- and neurobiological impairments. Here, we treated adolescent, male rats with olanzapine on post-natal days 28-49. As adults, they exhibited impaired working memory, but normal spatial memory, as compared to vehicle-treated control rats. They also showed a deficit in extinction of fear conditioning. Measures of motor activity and skill, habituation to an open field, and affect were normal. In the orbital- and medial prefrontal cortices, parietal cortex, nucleus accumbens core and dentate gyrus, adolescent olanzapine treatment altered the developmental dynamics and mature values of dendritic spine density in a region-specific manner. Measures of motor activity and skill, habituation to an open field, and affect were normal. In the orbital- and medial prefrontal cortices, D1 binding was reduced and binding of GABA(A) receptors with open Cl(-) channels was increased. In medial prefrontal cortex, D2 binding was also increased. The persistence of these changes underscores the importance of improved understanding of the enduring sequelae of pediatric APD treatment as a basis for weighing the benefits and risks of adolescent antipsychotic drug therapy, especially prophylactic treatment in high risk, asymptomatic patients. The long-term changes in neurotransmitter receptor binding and neural circuitry induced by adolescent APD treatment may also cause enduring changes in behavioral- and neurobiological responses to other therapeutic- or illicit psychotropic drugs.
    PLoS ONE 02/2013; 8(2):e57308. DOI:10.1371/journal.pone.0057308 · 3.23 Impact Factor
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