Antipsychotics use in children and adolescents: An on-going challenge in clinical practice

Abstract

Antipsychotic medications (APs) are a well-established pharmacological treatment in adults with serious mental health problems. However, many adult mental health disorders have their origins and onset in childhood or adolescence. The understanding that neuropsychiatric conditions of childhood are in part biologically determined, led to an increase in the number of clinical trials supporting evidence on the efficacy of antipsychotic agents as first-line treatment for childhood psychotic disorders and therapeutic augmentation of nonpsychotic conditions. In recent years the use of antipsychotics in children and adolescents for neurodevelopmental, behavioural and psychiatric disorders has significantly increased while the age of prescription has decreased. These trends have not been matched by advances in the understanding of APs' safety profile in this group of patients. It is therefore crucial that current and future practice is informed by up-to-date synthesis of the evidence and clinical guidelines about the use and monitoring of these treatments in paediatric populations, since the effectiveness of early therapeutic interventions in children can affect positively the long-term outcome.

Persistence of racial disparities in prescription of first-generation antipsychotics in the USA

“…Antipsychotics are most often indicated for schizophrenia and the acute manic phase of bipolar disorder, but “off‐label” uses include obsessive‐compulsive and refractory depression, with some SGA approved for major depressive disorder beginning with aripiprazole in late 2007 . Off‐label use of SGA has increased for the treatment of agitation in Alzheimer's disease, Parkinson's disease, and childhood‐onset development disorders . The use of clozapine, the first SGA, may be contraindicated based on low white blood cell counts, requiring routine blood monitoring, a problem more common among Black patients .…”

Metabolic Side Effects and Pharmacogenetics of Second-Generation Antipsychotics in Children

“…HTR2C rs3813929 -759C/T No effect of the T allele on weight, zBMI, or metabolic parameters from initiation of risperidone treatment to current assessment [73] 11.8 ± 2.8 years (mean ± SD) Several studies investigating genetic factors that may predispose an SGA-treated child to develop cardiometabolic side effects have targeted serotonin signaling and focused on the 5-HTR2C because many SGAs are antagonists for this receptor [24], mice deficient in 5-HTR2C develop obesity [97], and a meta-analysis of studies in adults report an association between a variant in the promoter region of 5HTR2C, -759C/T (rs3813929) and SGA-related weight gain [98]. The 5HTR2C gene is X-linked; therefore, males are hemizygous for the C or T allele.…”

Safety and Tolerability of Antipsychotics

“…Most antipsychotic drugs prescribed for children are also "off-label" that include use in aggression and irritability in patients with autism, conduct disorders, and pervasive developmental disorders with an increasing frequency (Schneider et al 2014 ). Antipsychotic use in clinical practice especially in young children as early as Chlorpromazine 3 2 2 3 3 Fluphenazine 4 2 1 2 2 Haloperidol 3 3 0 1 1 Loxapine 3 2 1 2 2 Mesoridazine 3 3 1 3 2 Perphenazine 4 3 0 3 2 Thioridazine 3 3 2 2 3 Second-generation typical antipsychotics Aripiprazole 4 3 0 2 1 Asenapine 3 3 0 2 3 Clozapine 1 4 3 4 2 Iloperidone 3 4 0 2 4 Lurasidone 3 3 0 0 4 Olanzapine 2 3 2 4 1 Paliperidone 3 3 0 3 2 Quetiapine 1 2 0 2 2 Risperidone 3 4 0 3 3 Ziprasidone 3 4 0 2 1 0 = negligible, 1 = low, 2 = moderate, 3 = moderate high, 4 = high, reference compound; EPS extrapyramidal side effects D2 = dopamine receptor subtype, 5Ht2A = serotoninergic receptor subtype 2A, M = muscarinic receptor, H1 = histamine receptor subtype 1, Alpha-1 = alpha adrenergic receptor subtype 1 2 years of age presents on-going challenges to healthcare systems.…”