Publisher's Synopsis
The purpose of this future research needs (FRN) report is to develop a list of stakeholders' research needs related to the comparative effectiveness of first- and second-generation antipsychotics (FGAs and SGAs) in pediatric and young adult populations. This FRN report is based on an Agency for Healthcare Research and Quality (AHRQ) comparative effectiveness review (CER) titled "First- and Second-Generation Antipsychotics for Children and Young Adults." We reviewed the CER in draft form. The purpose of the CER was to review and synthesize the evidence regarding the benefits and harms of FGAs and SGAs for the treatment of various psychiatric and behavioral conditions in children and young adults 24 years of age or younger. FGAs and SGAs are commonly categorized into two classes. FGAs, also known as typical antipsychotics, were developed in the 1950s. FGAs are used to treat psychotic symptoms such as auditory and visual hallucinations and delusions through several proposed mechanisms, including through the blockade of dopamine neuro-receptors. FGAs are associated with various adverse effects. These side effects include extra-pyramidal symptoms (EPS). EPS is a group of movement disorders, including acute dystonic reactions (severe spasms of various muscle groups), akathisia (a feeling of motor restlessness), pseudo-parkinsonism (medication-induced motor slowness and rigidity), and tardive dyskinesia (repetitive low amplitude movements, most often of facial muscles, insidious and chronic in nature). The most severe antipsychotic-associated potential side effect is neuroleptic malignant syndrome (NMS), characterized by hyperthermia, rigidity, rhabdomyolysis, renal failure, delirium, cardiovascular instability, and death. SGAs, also known as atypical antipsychotics, emerged in the 1980s. SGAs are generally thought to have a lower risk of EPS. The risk of NMS is rare for both medication classes, and researchers are uncertain about whether there is an intra-class risk difference for NMS. However, SGAs are associated with a higher risk of a range of metabolic side effects, including weight gain; dyslipidemia; insulin resistance; the development of type 2 diabetes; and, rarely, hyperglycemic coma. The review1 was prompted by the observation that the use of antipsychotics, particularly SGAs, for children and adolescents has increased markedly during the past 20 years. Prescribing antipsychotics to the pediatric population is controversial because of a relative lack of high-quality and longitudinal studies on which to base clinical practice recommendations. For the majority of antipsychotic drugs, approved indications in the United States are restricted to the treatment of childhood schizophrenia and bipolar disorders. The U.S. Food and Drug Administration (FDA) approved risperidone in 2006 and aripiprazole in 2009 for the treatment of irritability associated with autism. Off-label prescriptions are given to younger children for a range of indications including behavioral symptoms (e.g., aggression) that are related to diagnosable conditions (e.g., attention deficit hyperactivity disorder [ADHD]). In general, much prescribing of SGAs for children and adolescents does not appear to be guided by evidence of clinical benefit or risk of harms.
