Adverse psychological effects of corticosteroids in children and adolescents

Child and Family Department, Tavistock Centre, 120 Belsize Lane, London NW3 5BA, UK.
Archives of Disease in Childhood (Impact Factor: 2.9). 06/2005; 90(5):500-6. DOI: 10.1136/adc.2003.041541
Source: PubMed


Children and adolescents treated with oral, inhaled, and intravenous corticosteroids (CS) may experience adverse psychological side effects (APSE), including psychotic symptoms. These can occur at any point during treatment, including withdrawal. In this paper the literature on these effects in children and adults is reviewed. From the evidence available, it is not possible to give reliable estimates for incidence or prevalence of APSE, nor clear risk factors. Some evidence is reported to suggest that oral dexamethasone treatment may carry a higher risk of APSE than other CS, but this requires further investigation. There is evidence from the adult literature that higher CS doses increase the risk of APSE. However, the dose response effect is not straightforward or predictable for individuals or groups. This is likely to be a reflection of the complex effects of CS on the central nervous system and the probable interplay between individual susceptibility, disease factors, and external environmental stressors in the emergence of APSE. More research is required to further our understanding of the adverse effects of these clinically valuable agents.

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Available from: Terry Y Segal, Jan 13, 2015
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    • "In humans, memory deficits have been found in clinical conditions characterized by prolonged exposure to elevated glucocorticoids, such as Cushing syndrome (for a review, see Sapolsky, 2000) and in individuals receiving glucocorticoid treatment (Lupien et al., 2007; Stuart et al., 2005). In healthy adults, glucocorticoid manipulations have also been found to influence memory, particularly working memory—the shortterm storage and manipulation of information (Baddeley, 1992). "
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    ABSTRACT: Individuals with classic congenital adrenal hyperplasia (CAH) experience impaired glucocorticoid production and are treated postnatally with glucocorticoids. Prior research with animals and other human populations indicates that glucocorticoids can influence memory, particularly working memory. We tested the hypothesis that children with CAH would show reduced working memory. Children in the United Kingdom, aged 7-11 years, with classical CAH (31 girls, 26 boys) were compared to their unaffected relatives (30 girls, 20 boys) on a test of working memory, the Digit Span test. Vocabulary was also assessed to measure verbal intelligence for control purposes. Children with CAH showed reduced working memory performance compared to controls, on both components of the Digit Span test: p=.008 for Digit Span Forward, and p=.027 for Digit Span Backward, and on a composite score, p=.004. These differences were of moderate size (d=.53 to .70). Similar differences were also seen in a subset of 23 matched pairs of children with CAH and their relatives (d=.78 to .92). There were no group differences on Vocabulary. Glucocorticoid abnormality, including treatment effects, could be responsible for the reduced Digit Span performance in children with CAH. Other factors related to CAH, such as salt-wasting crises, could also be involved. Additional research is needed to identify the cause of the memory reduction, which will help to determine if more rapid diagnosis or more precise glucocorticoid treatment would help prevent memory reduction. Educational interventions might also be considered for children with CAH. Copyright © 2014. Published by Elsevier Inc.
    Full-text · Article · Dec 2014 · Hormones and Behavior
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    • "Although the pathophysiology of these side effects is still not fully understood, some authors have proposed potential glucocorticoid-related hippocampus damage as the cause [15]. Concerns have been raised regarding the potential for hippocampus damage that is not completely reversible in some children treated with corticosteroids (especially those on the highest doses and long-term therapies), with possible long-lasting negative effects on cognition, but no longitudinal studies have been performed to clarify the cognitive outcomes in these patients [16]. "
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    ABSTRACT: Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency) has been reported with neurological and magnetic resonance imaging (MRI) abnormalities (e.g., delayed myelination and brain atrophy) due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH), a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF) pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS) through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric) CNS seems to be particularly vulnerable to alterations induced by adrenal disorders and/or supraphysiological doses of corticosteroids. Physicians should be aware of potential neurological manifestations in children with adrenal dysfunction to achieve better prevention and timely diagnosis and treatment of these disorders. Further studies are needed to explore the potential neurological, cognitive, and psychiatric long-term consequences of high doses of prolonged corticosteroid administration in childhood.
    Full-text · Article · Sep 2014 · International Journal of Endocrinology
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    • "Studies on glucocorticoid-related psychosocial morbidity, although often clinically evident, in children are sparse. A review on this subject by Stuart et al. [9] in 2005, yielded ten larger studies, only two of which concerned childhood ALL, and several case-reports. Possible steroid-related side effects include emotional lability, anxiety, aggressive behaviour, hyperactivity, depression [10,11], problems with concentration, excessive eating [12], increase in pain [13] and sleep disorders [14]. "
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    ABSTRACT: Glucocorticoids are important in the treatment of childhood acute lymphoblastic leukaemia (ALL). However, cyclic administration of high dose glucocorticoids may cause rapid and substantial changes in quality of life (QoL). The maintenance phase of the Dutch ALL-9 protocol consisted of alternating two weeks on and five weeks off dexamethasone (6 mg/m(2)/day). The present study was performed to assess the effect of dexamethasone on QoL during treatment for ALL according to this protocol. In a multicentre prospective cohort study, QoL was assessed halfway (T1) and at the end of the two-year treatment (T2). A generic (Child Health Questionnaire) and disease specific (PedsQL cancer version) QoL questionnaire were used to assess QoL in two periods: on and off dexamethasone, respectively. 41 children (56% males) were evaluated, mean age at diagnosis was 5.6 years. The CHQ physical and psychosocial summary scores were significantly lower than population norms. At T1 and T2, overall QoL showed no significant change. However, regarding specific domains (pain, cognitive functioning, emotion/behaviour and physical functioning) QoL decreased over time. QoL was significantly more impaired during periods on dexamethasone. Dexamethasone was associated with decreased QoL. At the end of treatment, reported QoL during dexamethasone deteriorated even more on certain scales (pain, cognitive functioning, emotion/behaviour and physical functioning). Knowledge of the specific aspects of QoL is essential to improve counselling and coping in paediatric oncology. Adverse effects of specific drugs on QoL should be taken into account when designing treatment protocols.
    Full-text · Article · Dec 2008 · Health and Quality of Life Outcomes
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