Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study

Abstract

Aims The risk of antipsychotic-associated cardiovascular and metabolic events may differ among countries, and limited real-world evidence has been available comparing the corresponding risks among children and young adults. We, therefore, evaluated the risks of cardiovascular and metabolic events in children and young adults receiving antipsychotics. Methods We conducted a multinational self-controlled case series (SCCS) study and included patients aged 6–30 years old who had both exposure to antipsychotics and study outcomes from four nationwide databases of Taiwan (2004–2012), Korea (2010–2016), Hong Kong (2001–2014) and the UK (1997–2016) that covers a total of approximately 100 million individuals. We investigated three antipsychotics exposure windows (i.e., 90 days pre-exposure, 1–30 days, 30–90 days and 90 + days of exposure). The outcomes were cardiovascular events (stroke, ischaemic heart disease and acute myocardial infarction), or metabolic events (hypertension, type 2 diabetes mellitus and dyslipidaemia). Results We included a total of 48 515 individuals in the SCCS analysis. We found an increased risk of metabolic events only in the risk window with more than 90-day exposure, with a pooled IRR of 1.29 (95% CI 1.20–1.38). The pooled IRR was 0.98 (0.90–1.06) for 1–30 days and 0.88 (0.76–1.02) for 31–90 days. We found no association in any exposure window for cardiovascular events. The pooled IRR was 1.86 (0.74–4.64) for 1–30 days, 1.35 (0.74–2.47) for 31–90 days and 1.29 (0.98–1.70) for 90 + days. Conclusions Long-term exposure to antipsychotics was associated with an increased risk of metabolic events but did not trigger cardiovascular events in children and young adults.

Antipsychotics in the Management of Disruptive Behavior Disorders in Children and Adolescents: An Update and Critical Review

“…The observation that around one quarter of trial participants gained over 5% of their baseline body weight over a longer treatment period is a cause for greater concern, though this figure was based on a single trial and requires replication [ 49 ]. Likewise, the elevations in serum cholesterol and prolactin represent a significant adverse effect, as they could contribute to subsequent medical conditions, such as metabolic syndrome [ 68 ] or osteoporosis [ 69 ], if antipsychotic therapy is administered for a prolonged period. A severe adverse effect of particular concern identified in recent study data was neutropenia, which was specifically associated with clozapine but was also reported in association with a child receiving risperidone therapy [ 38 , 40 ].…”

Antipsychotics in the Management of Disruptive Behavior Disorders in Children and Adolescents: An Update and Critical Review

“…The observation that around one-fourth of trial participants gained over 5% of their baseline body weight over a longer treatment period is a cause for greater concern, though this figure was based on a single trial and requires replication [39]. Likewise, the elevations in serum cholesterol and prolactin represent a significant adverse effect, as they could contribute to subsequent medical conditions such as metabolic syndrome [57] or osteoporosis [58] if antipsychotic therapy is administered for a prolonged period. A severe adverse effect of particular concern identified in recent study data was neutropenia, which was specifically associated with clozapine but was also reported in association with a child receiving risperidone therapy [38,40].…”

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders

“…We designed an online questionnaire to collect information about the databases available to NeuroGEN researchers. The survey included 132 questions covering the following categories: (1) database characteristics (4 questions), (2) accessibility to the participating databases (7 questions), (3) patient information (29 questions), (4) healthcare facility visit details (5 questions), (5) diagnosis details (7 questions), (6) drug details (16 questions), (7) procedure details (5 questions), (8) laboratory examination details (5 questions), (9) claims details (9 questions), (10) information on alternative medicine (17 questions), (11) hospital details (9 questions), (12) physician details (10 questions) and (13) details on other healthcare professionals (9 questions). The survey was emailed to key researchers and data custodians in each NeuroGEN member organization.…”

“…For example, in older patients, the use of antipsychotics has been associated with mortality risk 10,11 and psychotropic medications have been associated with sedation, falls, arrhythmia, metabolic syndromes and extrapyramidal symptoms. [12][13][14] In pregnant women, the use of some anticonvulsants such as valproates has been associated with an increased risk of congenital and neurodevelopmental disorders in the offspring. 15 These issues underscore the importance of proper assessment of safety and effectiveness of new and existing treatments for neurological and mental disorders.…”