First- and Second- Generation Antipsychotics for Children and Young Adults [Entered Retrospectively]

Project Summary Title and Description

Title
First- and Second- Generation Antipsychotics for Children and Young Adults [Entered Retrospectively]
Description
Methods: Two reviewers conducted study selection and quality assessment independently and resolved discrepancies by consensus. One reviewer extracted data, and a second reviewer verified the data. We conducted a descriptive analysis for all studies and performed metaanalyses when appropriate. Results: Eighty-one studies (64 trials and 17 cohort studies) examined the following conditions: pervasive developmental disorders (12 studies); attention deficit hyperactivity disorder (ADHD) or disruptive behavior disorders (8 studies); bipolar disorder (11 studies); schizophrenia and related psychosis (31 studies); Tourette syndrome (7 studies); behavioral issues (4 studies); and multiple conditions (9 studies). One study reported data on both bipolar disorder and schizophrenia. The majority of the trials had a high risk of bias. The methodological quality of the cohort studies was moderate. Results are presented by outcome below: Symptoms: The strength of evidence for all head-to-head comparisons of FGAs and SGAs was low or insufficient to draw conclusions. SGAs were favored over placebo for behavior symptoms (ADHD and disruptive behavior disorders), the Clinical Global Impressions scale (ADHD and disruptive behavior disorders, bipolar disorder, and schizophrenia), positive and negative symptoms (schizophrenia), and tics (Tourette syndrome) (moderate strength of evidence). Other short- and long-term outcomes: All head-to-head comparisons had low or insufficient strength of evidence. There was no significant difference between SGAs and placebo for suicide related behaviors (moderate strength of evidence). The evidence was rated as insufficient to draw conclusions for health-related quality of life, involvement with the legal system, and other patient-, parent-, or care provider-reported outcomes for all conditions. Adverse events: All outcomes comparing FGAs with SGAs had low or insufficient strength of evidence. Outcomes comparing FGAs versus FGAs and FGAs versus placebo had insufficient evidence. Risperidone was favored over olanzapine for dyslipidemia; olanzapine was favored over risperidone for prolactin-related events; and both quetiapine and risperidone were favored over olanzapine for weight gain (moderate strength of evidence). For nearly all outcomes and comparisons, placebo resulted in significantly fewer adverse events than SGAs. Subpopulations: Thirty-six studies examined the association between various patient subpopulations and outcomes. Most concluded that the results did not differ by subpopulations, or findings were discordant across studies. Conclusion: Evidence comparing FGAs with SGAs, various FGAs, and FGAs with placebo was very limited. Some SGAs appear to have a better side-effect profile than other SGAs. Compared with placebo, SGAs have better symptom improvement but more adverse events. Future high quality research examining head-to-head antipsychotic comparisons is needed.
Attribution
N/A
Authors of Report
N/A
Methodology description
We systematically searched the following bibliographic databases: MEDLINE, Embase, CENTRAL, PsycINFO, International Pharmaceutical Abstracts (IPA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, ProQuest Dissertations International, MedEffect Canada, and TOXLINE. The searches are up to date to February 2011. We limited the searches to studies published from 1987 or later to coincide with the Diagnostic and Statistical Manual of Mental Disorders III–Revised. We restricted the search results to studies published in the English language. We applied filters to restrict the results to children and young adults ≤24 years of age and to trials and cohort studies. We hand searched proceedings of the following scientific meetings that were identified by our clinical experts: American Academy of Child and Adolescent Psychiatry (2007–2008), International College of Neuropsychopharmacology (2007–2009), and International Society for Bipolar Disorders (2007–2009). We searched clinical trial registers for ongoing studies and reference lists of relevant studies to identify additional studies. In addition, we contacted drug manufacturers to request published and unpublished study data. We reviewed FDA documents related to the eligible drugs to identify additional data. Two reviewers independently screened titles and abstracts using broad inclusion criteria. We retrieved the full text of all articles identified as "include" or "unclear." Two reviewers independently assessed each article using a priori inclusion criteria and a standardized form. We resolved disagreements by consensus or third-party adjudication. Randomized controlled trials (RCTs), nonrandomized controlled trials (NRCTs), and cohort studies that examined a condition of interest (pervasive developmental disorders, ADHD and disruptive behavior disorders, bipolar disorder, schizophrenia or schizophrenia-related psychosis, Tourette syndrome, obsessive-compulsive disorder, post-traumatic stress disorder, anorexia nervosa, or behavioral issues) in children or young adults ≤24 years of age were considered for inclusion. Eligible studies compared a FDA-approved FGA or SGA with any other antipsychotic or with placebo. Studies were required to report at least one outcome of interest including symptom improvement, other short- or long-term outcomes, or adverse events. No minimum follow-up duration was specified. One reviewer extracted data using a standardized form, and a second reviewer verified the data for accuracy and completeness. We extracted information on study characteristics, inclusion and exclusion criteria, participant characteristics, interventions, and outcomes. Reviewers resolved discrepancies by consensus or in consultation with a third party.
PROSPERO
N/A
DOI
10.7301/Z05Q4T1R
Notes
The systematic review data of this published project was retrospectively imported into SRDR by the Brown EPC on behalf of the Alberta EPC and the Agency for Healthcare Research and Quality (AHRQ). For access to the full report available on the AHRQ website, follow this link:http://effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=835
Funding Source
The Agency for Healthcare Research and Quality (AHRQ)

Key Questions

1. Key Question 1 - What is the comparative efficacy or effectiveness of FGAs and SGAs for treating disorder or illness-specific and nonspecific symptoms in children, youth, and young adults (≤24 years) for the following disorders or illnesses? ** Pervasive developmental disorders, including autistic disorder, Rett's disorder, childhood disintegrative disorder, Asperger's disorder, and pervasive developmental disorder not otherwise specified. ** ADHD and disruptive behavior disorders, including conduct disorder, oppositional defiant disorder, and disruptive behavior disorder not otherwise specified. ** Pediatric bipolar disorder, including manic or depressive phases, rapid cycling, and mixed states. ** Schizophrenia and schizophrenia-related psychoses, including schizoaffective disorder and drug-induced psychosis. ** Obsessive-compulsive disorder. ** Post-traumatic stress disorder. ** Anorexia nervosa. ** Tourette syndrome. ** Behavioral issues, including aggression, agitation, anxiety, behavioral dyscontrol,
2. Key Question 2 - Do FGAs and SGAs differ in medication-associated adverse events when used in children, youth, and young adults (≤24 years)? This includes: ** Overall adverse events. ** Specific adverse events. ** Withdrawals and time to withdrawal due to adverse events. ** Persistence and reversibility of adverse events.
3. Key Question 3 - Do FGAs and SGAs differ in other short- and long-term outcomes when used in children, youth, and young adults (≤24 years)? Short-term is defined as outcomes occurring within 6 months; long-term is defined as outcomes occurring after 6 months.
4. Key Question 4 - Do the effectiveness and risks of FGAs and SGAs vary in differing subpopulations including: ** Sex ** Age group (<6 years [preschool], 6–12 years [preadolescent], 13–18 years [adolescent], 19–24 years [young adult]) ** Race ** Comorbidities, including substance abuse and ADHD ** Cotreatment versus monotherapy ** First-episode psychosis versus treatment in context of history of prior episodes (related to schizophrenia) ** Duration of illness ** Treatment naïve versus history of previous antipsychotics use

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study.
A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia.
Control of psychomotor agitation and aggressive behavior in patients with autistic disorder: a retrospective chart review.2008
Clozapine and "high-dose" olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison.2008
Risperidone for the treatment of acute mania in children and adolescents with bipolar disorder: a randomized, double-blind, placebo-controlled study.
A double-blind, placebo-controlled pilot study of quetiapine for depressed adolescents with bipolar disorder.2009
Efficacy, safety and tolerability of two dosing regimens in adolescent schizophrenia: double-blind study.2009
Risperidone versus haloperidol in children and adolescents with AD : a randomized, controlled, double-blind trial.2008
Olanzapine compared to quetiapine in adolescents with a first psychotic episode.2009
Orally disintegrating olanzapine induces less weight gain in adolescents than standard oral tablets.2007
Tolerability of oral ziprasidone in children and adolescents with bipolar mania, schizophrenia, or schizoaffective disorder.2008
A comparative pilot study of second-generation antipsychotics in children and adolescents with schizophrenia-spectrum disorders.2008
Randomized controlled pilot study of quetiapine in the treatment of adolescent conduct disorder.
Dosing quetiapine in drug-naive first-episode psychosis: a controlled, double-blind, randomized, single-center study investigating efficacy, tolerability, and safety of 200 mg/day vs. 400 mg/day of quetiapine fumarate in 141 patients aged 15 to 25 years.
Metabolic and hormonal side effects in children and adolescents treated with second-generation antipsychotics.2008
Acute treatment of pediatric bipolar I disorder, manic or mixed episode, with aripiprazole: a randomized, double-blind, placebo-controlled study.2009
Aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder: a pilot randomized clinical trial.
A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia.
Olanzapine versus placebo in adolescents with schizophrenia: a 6-week, randomized, double-blind, placebo-controlled trial.2009
Weight gain associated with atypical and typical antipsychotics during treatment of adolescent schizophrenic psychoses: A retrospective study.2009
Effects of risperidone on cognitive-motor performance and motor movements in chronically medicated children.-- Not Found --
A randomized, double-blind, placebo-controlled study of risperidone maintenance treatment in children and adolescents with disruptive behavior disorders.
Olanzapine versus placebo in the treatment of adolescents with bipolar mania.2007
Childhood-onset schizophrenia: A double-blind, randomized clozapine-olanzapine comparison.
Open-label, 8-week trial of olanzapine and risperidone for the treatment of bipolar disorder in preschool-age children.
A crossover study of risperidone in children, adolescents and adults with mental retardation.
Risperidone in preschool children with autistic spectrum disorders: an investigation of safety and efficacy.
A double-blind placebo-controlled pilot study of olanzapine in childhood/adolescent pervasive developmental disorder.2006
An open-label randomized comparison of olanzapine versus risperidone in the treatment of childhood-onset schizophrenia.2006
Risperidone in children with autism: randomized, placebo-controlled, double-blind study.
Long-term effects of risperidone in children with autism spectrum disorders: a placebo discontinuation study.
Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence.2002
Weight gain associated with increased food intake and low habitual activity levels in male adolescent schizophrenic inpatients treated with olanzapine.
Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study.
Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome.2003
Symptom response and side-effects of olanzapine and risperidone in young adults with recent onset schizophrenia.2003
A double-blind, randomized, placebo-controlled study of quetiapine as adjunctive treatment for adolescent mania.2002
Effects of risperidone on conduct and disruptive behavior disorders in children with subaverage IQs.2002
Tic reduction with risperidone versus pimozide in a randomized, double-blind, crossover trial.2004
A placebo-controlled trial of risperidone in Tourette syndrome.2003
A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a double-blind, randomized, 8-week trial.2004
Risperidone in children with autism and serious behavioral problems.
Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders.
Relative efficacy of haloperidol and pimozide in children and adolescents with Tourette's disorder.1997
Childhood-onset schizophrenia. A double-blind clozapine-haloperidol comparison.1996
Atypical antipsychotic use in treating adolescents and young adults with developmental disabilities.2001
Correlated changes in symptoms and neurotransmitter indices during maintenance treatment with clozapine or conventional neuroleptics in adolescents and young adults with schizophrenia.1996
Risperidone in the treatment of behavioral disturbances in children and adolescents with borderline intellectual functioning: a double-blind, placebo-controlled pilot trial.2001
Risperidone versus pimozide in Tourette&#x27;s disorder: a comparative double-blind parallel-group study.
Risperidone versus pimozide in Tourette&#x27;s disorder: a comparative double-blind parallel-group study.
Childhood-onset schizophrenia: an open-label study of olanzapine in adolescents.
A double-blind pilot study of risperidone in the treatment of conduct disorder.
Ziprasidone treatment of children and adolescents with Tourette&#x27;s syndrome: a pilot study.
Olanzapine versus haloperidol in children with autistic disorder: an open pilot study.2001
Effects of pimozide on cognition in children with Tourette syndrome: interaction with comorbid attention deficit hyperactivity disorder.1994
Long-term efficacy of haloperidol in autistic children: continuous versus discontinuous drug administration.1989
Children with schizophrenia: diagnosis, phenomenology, and pharmacotherapy.1994
A trial of quetiapine compared with risperidone in the treatment of first onset psychosis among 15- to 18-year-old adolescents.2010
Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents.2009
A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder.
A non-randomized, open study with aripiprazole and ziprasidone for the treatment of aggressive behavior in youth in a community clinic.
Use and tolerability of newer antipsychotics and antidepressants: a chart review in a paediatric setting.2008
Clinical drug monitoring in child and adolescent psychiatry: side effects of atypical neuroleptics.2006
Weight gain associated with olanzapine and risperidone in adolescent patients: a comparative prospective study.2002
Elevated prolactin in pediatric patients on typical and atypical antipsychotics.1999
Risperidone augmentation for treatment-resistant aggression in attention-deficit/hyperactivity disorder: a placebo-controlled pilot study.
Atypical antipsychotics.1998
Short-term versus longer term pimozide therapy in Tourette's syndrome: a preliminary study.1999
A naturalistic evaluation of intramuscular ziprasidone versus intramuscular olanzapine for the management of acute agitation and aggression in children and adolescents.2006
Adverse effects of risperidone and haloperidol treatment in schizophrenia.2004
Four week, double-blind, placebo controlled phase III trial evaluating the efficacy, safety and pharmacokinetics of flexible doses of oral ziprasidone in children and adolescents with bipolar I disorder (manic or mixed). PhRMA Web Synopsis 2008.2010
Six week, double-blind, placebo controlled phase III trial evaluating the efficacy, safety and pharmacokinetics of flexible doses of oral ziprasidone in adolescent subjects with schizophrenia. PhRMA Web Synopsis 2010.20032
A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia.2008
A 6-week, international, multicenter, randomized, double-blind, parallel-group, placebo-controlled, phase IIIb study of the efficacy and safety of quetiapine fumarate immediate-release tablets in daily doses of 400 mg and 800 mg compared with placebo in the treatment of adolescents with schizophrenia. Clinical study report synopsis 2008. 2008
A 6-week, randomized, double-blind, placebo-controlled study of the efficacy and safety of risperidone in adolescents with schizophrenia.
Short- and long-term effects on prolactin of risperidone and olanzapine treatments in children and adolescents.2009
A prospective study of hyperprolactinemia in children and adolescents treated with atypical antipsychotic agents.2004
Open-label study to evaluate the safety and pharmacokinetics of single- and multiple-dose extended-release paliperidone in pediatric subjects (10 to 17 years of age) with schizophrenia, schizoaffective disorder, or schizophreniform disorder. Johnson & Johnson Pharmaceutical Research & Development 2007.2007
Open-label, 8-week trial of olanzapine and risperidone for the treatment of bipolar disorder in preschool-age children.2005
Risperidone in the treatment of children and adolescents with autistic disorder: A double-blind, placebo-controlled study of efficacy and safety, followed by an open-label extension study of safety. Clinical study report synopsis 2010.2010
A 3-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled study of the efficacy and safety of quetiapine fumarate immediate release tablets in daily doses of 400 mg and 600 mg compared with placebo in the treatment of children and adolescents with bipolar I mania. Clinical study report synopsis 2006.2008

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