Safety and tolerability of antipsychotic agents in neurodevelopmental disorders: a systematic review

Iasevoli, Felice; Barone, Annarita; Buonaguro, Elisabetta Filomena; Vellucci, Licia; Bartolomeis, Andrea de

doi:10.1080/14740338.2020.1820985

Cited by 19 publications

(19 citation statements)

References 312 publications

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“…However, it is important to note that only two out of 18 included studies involved patients with IDD aged 18 years or older. This is consistent with the findings of a recent review that only identified two retrospective studies exclusively in adults 45 . This is interesting given that the existing literature suggests that patients with IDD are both over‐prescribed APs and kept on them for far longer than necessary 46 .…”

Section: Discussionsupporting

confidence: 90%

“…This is consistent with the findings of a recent review that only identified two retrospective studies exclusively in adults. 45 This is interesting given that the existing literature suggests that patients with IDD are both over-prescribed APs and kept on them for far longer than necessary. 46 In fact, as demonstrated by a large population-based cohort study, nearly 40% of adults with IDD are dispensed at least one AP over a 6-year period, and 30% of these individuals do not have any documented psychiatric diagnosis.…”

Section: Discussionmentioning

confidence: 99%

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The metabolic adverse effects of antipsychotic use in individuals with intellectual and/or developmental disability: A systematic review and meta‐analysis

Smith

Stogios

et al. 2022

Acta Psychiatr Scand

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Individuals with intellectual and/or developmental disability (IDD) are often prescribed antipsychotics (APs). However, despite their known propensity to cause metabolic adverse effects, including weight gain, diabetes, and increased risk of cardiovascular events, there is currently a limited body of literature describing the metabolic consequences of AP use in this population. Methods: We searched MEDLINE, EMBASE, PsychINFO, CENTRAL, and CINAHL databases to identify all randomized trials that reported on the metabolic effects of APs in individuals with IDD. Random effects meta-analyses were used to examine weight gain as both a continuous and dichotomous outcome.Results: Eighteen randomized trials met our inclusion criteria with a total of 1376 patients across a variety of IDDs. AP use was associated with significantly greater weight gain compared with placebo (Continuous: mean difference = 1.10 kg, [0.79, 1.40], p < 0.00001, I 2 = 54%; Dichotomous: odds ratio = 3.94, [2.15, 7.23], p < 0.00001, I 2 = 0). Sub-group analysis revealed no significant effect of AP type. Data regarding the effects of APs on other metabolic outcomes were limited. Conclusion: This review (PROSPERO # CRD42021255558) demonstrates that AP use is associated with significant weight gain among patients with IDD. Concerningly, most reported studies were in children and adolescents, which sets up an already vulnerable population for adverse medical sequalae at an early age. There was also a lack of long-term studies in adults with IDD. Further studies are required to better understand how AP use affects metabolic parameters in this group of individuals.Emily Smith and Nicolette Stogios shared first authorship.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

The metabolic adverse effects of antipsychotic use in individuals with intellectual and/or developmental disability: A systematic review and meta‐analysis

Smith

Stogios

et al. 2022

Acta Psychiatr Scand

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“…Several studies have investigated the potential efficacy of various psychoactive drugs to improve ASD symptoms, but these studies yielded mixed results (LeClerc and Easley 2015 ; Posey et al 2008 ). The potential side effects of antipsychotics in neurodevelopmental disorders have been reviewed by Lamy and Erickson ( 2018 ) and Iasevoli et al ( 2020 ), which concluded that side effects (e.g., weight gain, elevated prolactin levels, extrapyramidal symptoms, somnolence, sedation) may be milder in the younger population (e.g., less than 18 years of age) and less frequent due to lower doses; however, some subgroups may show hypersensitivity to these medications. The clinical results with cariprazine in adults show a beneficial safety profile concerning prolactin levels, sedation, electrocardiogram parameters, and metabolic parameters such as weight gain (Nasrallah et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Cariprazine alleviates core behavioral deficits in the prenatal valproic acid exposure model of autism spectrum disorder

et al. 2021

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Rationale Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction and restricted, repetitive behaviors. The unmet medical need in ASD is considerable since there is no approved pharmacotherapy for the treatment of these deficits in social communication, interaction, and behavior. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist, is already approved for the treatment of schizophrenia and bipolar I disorder in adults; investigation in patients with ASD is warranted. Objectives The aim of this study was to investigate the effects of cariprazine, compared with risperidone and aripiprazole, in the rat prenatal valporic acid (VPA) exposure model on behavioral endpoints representing the core and associated symptoms of ASD. Methods To induce the ASD model, time-mated Wistar rat dams were treated with VPA during pregnancy. Male offspring were assigned to groups and studied in a behavioral test battery at different ages, employing social play, open field, social approach-avoidance, and social recognition memory tests. Animals were dosed orally, once a day for 8 days, with test compounds (cariprazine, risperidone, aripiprazole) or vehicle before behavioral assessment. Results Cariprazine showed dose-dependent efficacy on all behavioral endpoints. In the social play paradigm, only cariprazine was effective. On the remaining behavioral endpoints, including the reversal of hyperactivity, risperidone and aripiprazole displayed similar efficacy to cariprazine. Conclusions In the present study, cariprazine effectively reversed core behavioral deficits and hyperactivity present in juvenile and young adult autistic-like rats. These findings indicate that cariprazine may be useful in the treatment of ASD symptoms.

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“…Aripiprazole may be preferred because it appears to cause less weight gain compared to risperidone. 91 Risperidone and amphetamines have also been studied as treatments for ADHD in intellectual disability and, on the basis of the current lack of robust evidence, are not recommended. 92,93 Other pharmacological treatments (olanzapine; beta-blockers for behavioural disorders; anti-depressants for depression; benzodiazepines for any outcome) have no evidence or are not recommended.…”

Section: Treatments and Interventions For Mental Health Problems In C...mentioning

confidence: 99%

“…92,93 Other pharmacological treatments (olanzapine; beta-blockers for behavioural disorders; anti-depressants for depression; benzodiazepines for any outcome) have no evidence or are not recommended. 91,[94][95][96] Some agents may even cause paradoxical effects (e.g. benzodiazepines causing disinhibition).…”

Section: Treatments and Interventions For Mental Health Problems In C...mentioning

confidence: 99%

Mental health problems in children with intellectual disability

Totsika

Liew

Absoud

et al. 2022

The Lancet Child & Adolescent Health

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Safety and tolerability of antipsychotic agents in neurodevelopmental disorders: a systematic review

Cited by 19 publications

References 312 publications

The metabolic adverse effects of antipsychotic use in individuals with intellectual and/or developmental disability: A systematic review and meta‐analysis

The metabolic adverse effects of antipsychotic use in individuals with intellectual and/or developmental disability: A systematic review and meta‐analysis

Cariprazine alleviates core behavioral deficits in the prenatal valproic acid exposure model of autism spectrum disorder

Mental health problems in children with intellectual disability

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