Antipsychotics for Children and Young Adults: A Comparative Effectiveness Review

Alberta Research Centre for Health Evidence, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.
PEDIATRICS (Impact Factor: 5.47). 03/2012; 129(3):e771-84. DOI: 10.1542/peds.2011-2158
Source: PubMed


Despite increasing on-label and off-label use of antipsychotics, prescribing antipsychotics to children remains controversial due to uncertainty of their relative benefits and safety. We systematically reviewed the effectiveness and safety of first- (FGA) and second-generation antipsychotics (SGA) for patients aged ≤24 years with psychiatric and behavioral conditions.
We searched 10 databases from January 1987 to February 2011, gray literature, trial registries, and reference lists. Two reviewers independently selected studies, assessed methodologic quality, and graded the evidence. One reviewer extracted, and a second verified, data. We summarized findings qualitatively and conducted meta-analyses when appropriate.
Sixty-four trials and 17 cohort studies were included. Most trials had a high risk of bias; cohort studies had moderate quality. All comparisons of FGAs versus SGAs, FGAs versus FGAs, and FGAs versus placebo had low or insufficient strength of evidence. There was moderate strength of evidence for the following comparisons. Olanzapine caused more dyslipidemia and weight gain, but fewer prolactin-related events, than risperidone. Olanzapine caused more weight gain than quetiapine. Compared with placebo, SGAs improved clinical global impressions (schizophrenia, bipolar and disruptive behavior disorders) and diminished positive and negative symptoms (schizophrenia), behavior symptoms (disruptive behavior disorders), and tics (Tourette syndrome).
This is the first comprehensive review comparing the effectiveness and safety across the range of antipsychotics for children and young adults. The evidence on the comparative benefits and harms of antipsychotics is limited. Some SGAs have a better side effect profile than other SGAs. Additional studies using head-to-head comparisons are needed.

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    • "The highest rates of cardiovascular effects have been reported for clozapine (40%) and quetiapine (13%) (U.S. Food and Drug Administration, 2000). Recent literature review by the Agency for Healthcare Research and Quality (AHRQ) had found limited evidence for the effectiveness of second-generation antipsychotics in the treatment of ADHD (Seida et al., 2012). AAP are increasingly used in children and adolescent with ADHD to control behavioral symptoms of ADHD and for the management of comorbid psychiatric conditions like bipolar disorders and other non-approved indications. "
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    ABSTRACT: Objective: This study examined cardiovascular safety of concomitant use of long-acting stimulants (LAS) and atypical antipsychotics (AAP) in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Method: The study used 2004-2007 IMS LifeLinkā„¢ claims data involving 6- to 16-year-old children with ADHD and at least one LAS prescription from July 2004 to December 2006. Time-dependent Cox regression analysis was performed to evaluate the risk of cardiovascular disease (CVD) events due to concomitant use of LAS and AAP. Results: The analytical cohort consisted of 37,903 children: 538 (1.9%) used LAS and AAP concurrently and the rest used LAS monotherapy. Time-dependent Cox regression analysis revealed no difference in CVD risk among concomitant users of LAS and AAP (hazard ratio = 1.19; 95% confidence interval = [0.60, 2.53]) when compared with users of LAS monotherapy. Conclusion: Concomitant use of LAS and AAP was not associated with risk of CVD events in ADHD patients when compared with LAS monotherapy.
    Journal of Attention Disorders 10/2015; DOI:10.1177/1087054715608443 · 3.78 Impact Factor
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    • "A ntipsychotics are a mainstay of treatment for people with serious mental illness including psychotic disorders (e.g., early psychosis, schizophrenia). Prescription of second generation antipsychotics to people under 25 years of age continues to increase (Alessi-Severini, Biscontri , Collins, Sareen, & Enns, 2012; Cooper et al., 2006; Harrison-Woolrych, Garcia-Quiroga, Ashton, & Herbison, 2007; Murphy et al., 2013; Olfson, Blanco, Liu, Wang, & Correll, 2012; Pringsheim, Lam, & Patten, 2011; Rani, Murray, Byrne, & Wong, 2008; Vitiello et al., 2009; Zito et al., 2008) despite controversy regarding effectiveness and safety data (Canadian Adverse Reaction Newsletter, 2012; Panagiotopoulos, Ronsley, Elbe, Davidson, & Smith, 2010; Pringsheim, Lam, Ching, & Patten, 2011; Seida et al., 2012). Young people's experiences of psychotropics, especially antipsychotics, have not been substantively explored . "
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    ABSTRACT: To explore the lived experience of youth who are prescribed antipsychotics. We conducted an interpretive phenomenology study of young people with recent experience of taking antipsychotics. Youth were interviewed and a staged approach was used for data analysis of transcriptions. We collected approximately 13 hours of audio from 18 youth aged 13 to 26 years between January and August of 2010. Ambivalence was significant and antipsychotic adverse effects frequently tempered benefits. Both illness and antipsychotics had significant impacts on physical and mental wellbeing with adverse effects on relationships and functioning in various contexts (e.g., school). Stigma related to both antipsychotics and illness was also prominent. Participants' limited knowledge about their antipsychotics and pressure to conform within their youth culture and context affected decisions on starting, adhering to, and persisting with treatment. The lived experience of youth taking antipsychotics is complex and the benefits (e.g., symptom improvement) and consequences (e.g., adverse effects) associated with antipsychotics affect all facets of life. More research is needed to better understand youth priorities in treatment decisions and whether youth who demonstrate substantive gaps in their knowledge about antipsychotics are truly given the opportunity to be informed and engage in management decisions including whether to initiate, persist with, and discontinue treatments.
    Journal of the Canadian Academy of Child and Adolescent Psychiatry = Journal de l'Academie canadienne de psychiatrie de l'enfant et de l'adolescent 09/2015; 24(1):61-9.
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    • "The authors of the study cautioned, however, that SGAs have a greater side-effect burden than mood stabilizers. The use of SGAs for bipolar depression is unclear, as some studies have demonstrated no difference in depressive symptoms when comparing SGAs to placebo.3 "
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    ABSTRACT: Objective To review the metabolic consequences of second-generation antipsychotics in youth and current monitoring and intervention guidelines for optimal treatment. Background Second-generation antipsychotics have largely replaced the use of first-generation antipsychotics in treating psychotic disorders in youth. In addition, there has been a dramatic increase in using these medications to treat a variety of nonpsychotic disorders. These medications have significant metabolic side effects, including weight gain. This raises concern, given the problem of pediatric obesity. Materials and methods A review of current literature looking at prescribing practices and possible reasons for the increased use of second-generation antipsychotics in children and adolescents was conducted. Review of the mechanisms for why youth may be particularly vulnerable to the metabolic consequences (particularly weight gain) was similarly completed. In addition, data supporting the efficacy, rationale, and unique side-effect profile of each individual second-generation drug were evaluated to help inform providers on when and what to prescribe, along with current monitoring practices. The current evidence base for possible interventions regarding the management of antipsychotic-induced weight gain was also evaluated. Results and conclusion On the basis of the literature review, there are several speculated reasons for the increase in prescriptions of second-generation antipsychotics. The choice of antipsychotic for youth should be based upon the disorder being treated along with the unique side-effect profile for the most commonly used second-generation antipsychotics. Monitoring strategies are also individualized to each antipsychotic. The current interventions recommended for antipsychotic-induced weight gain include lifestyle management, switching medication to a drug with a lower propensity for weight gain, and pharmacologic (particularly metformin) treatment.
    Adolescent Health, Medicine and Therapeutics 09/2014; 5:171-82. DOI:10.2147/AHMT.S49807
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