Larger concerns with antipsychotics in kids
Published in Health News and Evidence
Date published: About this date
Key points | Antipsychotic use is increasing | Risperidone indications are broader than most antipsychotics | Children are more prone to antipsychotic-induced adverse effects | Larger concerns with weight gain | Increased risk of metabolic syndrome | Extrapyramidal adverse effects and prolactin elevation | Monitor and manage adverse effects | Information for patients | References
Analysis of Australian PBS prescription data by the Drug Utilisation Sub-Committee (DUSC) has identified an increased use of atypical antipsychotics in children and adolescents despite limited data to support their efficacy and safety:
- between 2008 and 2011 there was a large increase in the use of quetiapine, with prescriptions for the 0–19-year age group more than doubling (an increase of 138%)
- risperidone use also increased in all age groups across this age category (+46%), and risperidone was the most commonly prescribed antipsychotic in children aged 14 years or younger
- monitoring of patients taking antipsychotics is reported to be suboptimal.
The indications for PBS-subsidised use of risperidone in children and adolescents aged < 18 years are broader than for most other antipsychotics, as treatment of autism is included; consequently the use of risperidone in very young children is a concern.
- Adverse effects from atypical antipsychotics are more severe in children and adolescents than in adults1
Atypical antipsychotics such as risperidone are TGA approved and PBS subsidised for use in children and adolescents but are associated with weight gain, metabolic, endocrine and extrapyramidal adverse effects more often in children than in adults.1-3
- A recent DUSC report identified an increasing number of adolescents and children prescribed antipsychotics despite limited data to support efficacy and safety4, 5
Little is known about efficacy and long-term harms associated with antipsychotic use, and clinical practice relies largely on extrapolation from adult data.5
- DUSC data showed risperidone was the most commonly prescribed antipsychiotic in children aged 14 years or younger4
The indications for PBS-subsidised use of risperidone are broader than for most other antipsychotics, as treatment of behavioural disturbances in autism is included.6
- Monitoring in patients taking antipsychotics is identified as suboptimal4, 7
GPs working closely with specialists play an important role in monitoring response to treatment and adverse effects and are well placed to educate patients and their carers about healthy lifestyle behaviours.
Analysis of Australian PBS prescription data shows a dramatic increase in prescribing of antipsychotics in people aged 0–19 years.4
Quetiapine prescriptions increased by 138%4
Between 2008 and 2011 there was a large increase in the use of quetiapine, with the number of patients prescribed the drug in the 0–19-year age group more than doubling (an increase of 138%).4
The study also noted a high level of use of low-dose quetiapine (25 mg formulation) in patients under 19.4 This is consistent with past DUSC reports identifying a higher than expected use of low-dose quetiapine among people aged 20–59 and in people with dementia in residential aged-care facilities.8
There are limited data concerning the adverse effects of low-dose quetiapine in children but data in adults show that even low-dose quetiapine is associated with adverse effects such as a significant increase in weight and body mass index.9, 10
Risperidone prescriptions increased by 46%4
In children aged 14 years or younger, risperidone was the most commonly prescribed antipsychotic.4
It was most often started as a single agent and prescribed mostly by specialists (including paediatricians).4
Note that these data may not reflect the full extent of the increase because some non-subsidised use, such as the treatment of disruptive behaviours in young children in the absence of autism, is not captured in the PBS database.5
In children and adolescents under 18 the indications for PBS-subsidised use for risperidone are broader than for most other antipsychotics.
Risperidone is PBS listed:6
- for schizophrenia
- for behavioural disturbance in patients with dementia when non-pharmacological methods have been unsuccessful
- as adjunctive therapy in the treatment of bipolar I disorder.
It may also be prescribed under the supervision of a paediatrician or psychiatrist, in combination with non-pharmacological measures, as initial treatment for severe behavioural disturbances in a patient with autism who is aged under 18.6
The increase in risperidone use may be due partly to the prevalence of autism spectrum disorders rising over recent years.11
Critical knowledge gaps
The rapid increase in use of antipsychotics in paediatric populations is a cause for concern — little is known about the long-term consequences of antipsychotic use in children and adolescents.
Few clinical trials have been undertaken in young people with mental illness and clinical practice relies largely on extrapolation from adult data.5
There is a need for randomised controlled trials and cohort studies that examine the long-term efficacy and safety of antipsychotics in this population to help guide antipsychotic decision making.12
Although introduced as a safer alternative to first-generation antipsychotics,13 atypical antipsychotics such as risperidone have metabolic, endocrine and extrapyramidal adverse effects, which appear to be more common in children than in adults.1, 3
Data available for some antipsychotic medicines used in children with autism and disruptive behaviour disorders suggest greater weight gain than for other indications, possibly due to less prior weight gain from less previous exposure to antipsychotics in this population.14
Measures to prevent and treat weight gain play a key role in patients’ management plans, to avoid adverse cardiometabolic outcomes.7
Children more sensitive to weight gain and associated risks
A review in which data were pooled from a variety of study designs found risperidone-induced weight gain as a percentage of baseline body weight was most pronounced in children and decreased with advancing age.2
Weight gain impacts self-esteem
Weight gain may negatively affect self-esteem, which may lead to non-adherence and poor quality of life and wellbeing.17 Furthermore, the sedative effect of these drugs may impair cognition and academic performance.
While trials exploring patient-important outcomes associated with antipsychotic use are lacking, consider the lasting impact of these adverse effects on health and development when prescribing in children.12
Children with age-inappropriate weight-gain and obesity after use of antipsychotic medicines are at risk of developing metabolic syndrome.7
Metabolic syndrome is a cluster of the most dangerous heart attack risk factors:18
- diabetes and prediabetes
- abdominal obesity
- high cholesterol
- high blood pressure.
Metabolic syndrome may occur soon after starting an antipsychotic
A US prospective study in more than 500 antipsychotic-naïve children and adolescents starting antipsychotics for psychotic and non-psychotic conditions showed that taking antipsychotics for only 10 weeks is associated with cardiometabolic adverse effects.19
Patients taking risperidone (n = 135) had significant weight gain over the first 3 months of treatment; the average weight gained was 5.4 kg. The study also found significant increases in dyslipidaemia and insulin resistance.
However, these results should be interpreted with caution, as the non-randomised observational design may have biased the reported outcomes.19
Nevertheless, metabolic syndrome presenting in children significantly increases the risk of early adult cardiovascular events because cardiovascular risk factors (eg, dyslipidaemia and increased blood pressure) are maintained from childhood into adulthood.20, 21
Children and adolescents appear to be more likely than adults to develop extrapyramidal adverse effects and hyperprolactinaemia when taking antipsychotics.22
Risperidone is one of the second-generation antipsychotics that produces a higher incidence of extrapyramidal adverse effects and hyperprolactinaemia.22
Males appear more susceptible to acute dystonias, and adolescent males may experience breast enlargement caused by elevated prolactin levels.3
When antipsychotics such as risperidone are used GPs play an important role in monitoring response to treatment and adverse effects and are well-placed to liaise with initiating specialists regarding these issues.3
GPs and other health professionals in regular contact with patients and their carers are in a good position to educate them on the importance of healthy lifestyle and to reinforce aspects such as diet and exercise.3
Recognise cardiometabolic risk factors early
Risk factors for metabolic adverse effects include:7
- family history of diabetes or heart disease
- certain ethnic populations (eg, Aboriginal and Torres Strait Islander peoples)
- those already overweight or obese, who may require more frequent monitoring.
Measure body mass index at baseline and periodically
In adolescents, BMI and BMI-for-age percentiles give a better indication of significant weight gain issues than by simply measuring weight.3
Obtain BMI-for-age percentiles according to gender, as this allows for norms that change with age and gender. Calculate using:3
- BMI-for-age percentile charts specific for boys and girls aged 2–20; charts are available from the Centers for Disease Control and Prevention;
- visit http://www.bcm.edu/cnrc/bodycomp/bmiz2.html a website that calculates BMI percentile for sex and age
BMI z scores
- > 5% BMI increase in the first 3 months
- any child falling into the overweight category (85th to 95th BMI percentile) with the presence of one other obesity-related complication (eg, hypertension, dyslipidaemia, hyperglycaemia)
- any child crossing into obesity (> 95th BMI percentile)
- ≥ 0.5 increase in BMI z score.
See Information for patients for further detail on healthy lifestyle behaviours.
Monitoring for prolactin elevation and sexual adverse effects
Due to the lack of evidence for the physiological risks of asymptomatic, subclinical prolactin elevations, current guidelines do not suggest routine prolactin monitoring or switching therapy, unless elevation is persistent (> 1000 mIU/L) and/or sexual adverse effects are present.22, 23
Most clinical symptoms are seen after puberty and include galactorrhoea and menstrual irregularities in females, and gynaecomastia, galactorrhoea and sexual dysfunction in males.22
In children hyperprolactinaemia may disrupt normal development, causing delayed pubertal maturation and decreased growth to cause short stature. There is also the potential to decrease bone mineral density and increase the risk of osteoporosis.22
Exclude other causes of raised prolactin levels such as pregnancy and breastfeeding in females, as well as stress, other medicines and tumours.22
Persistent elevations of prolactin > 2000–3000 mIU/L may indicate the presence of a pituitary tumour, as this has been associated with treatment with potent dopamine-2 receptor antagonists such as risperidone.22
Monitoring for extrapyramidal adverse effects
In children and adolescents antipsychotic-induced akathisia may present as difficulty falling asleep and can be mistaken for attention-deficit hyperactivity disorder.23
Extrapyramidal adverse effects are more likely to occur when higher doses are used.22
Educate patients about adverse effects and healthy lifestyle behaviours.
- Vitiello B, Correll C, van Zwieten-Boot B, et al. Antipsychotics in children and adolescents: increasing use, evidence for efficacy and safety concerns. Eur Neuropsychopharmacol 2009;19:629–35. [PubMed].
- Safer DJ. A comparison of risperidone-induced weight gain across the age span. J Clin Psychopharmacol 2004;24:429 [PubMed].
- Therapeutic Guidelines Psychotropic. Version 7, 2013. Melbourne: Therapeutic Guidelines Ltd (accessed 4 September 2014).
- Australian Government Department of Health. Antipsychotics in children and adolescents. 2013. (accessed 25 August 2014).
- Karanges EA, Stephenson CP, McGregor IS. Longitudinal trends in the dispensing of psychotropic medications in Australia from 2009–2012: Focus on children, adolescents and prescriber specialty. Aust N Z J Psychiatry 2014. [PubMed].
- Australian Government Department of Health. Pharmaceutical Benefits Scheme (PBS) – RISPERIDONE. (accessed 30 June 2014).
- Eapen V, Shiers D, Curtis J. Bridging the gap from evidence to policy and practice: reducing the progression to metabolic syndrome for children and adolescents on antipsychotic medication. Aust N Z J Psychiatry 2013;47:435–42. [PubMed].
- Australian Government Department of Health. DUSC Review on the Utilisation of Antipsychotics. August 2013 (accessed 14 March 2014).
- Cates ME, Jackson CW, Feldman JM, et al. Metabolic consequences of using low-dose quetiapine for insomnia in psychiatric patients. Community Ment Health J 2009;45:251–4. [PubMed].
- Williams SG, Alinejad NA, Williams JA, et al. Statistically significant increase in weight caused by low-dose quetiapine. Pharmacotherapy 2010;30:1011–5. [PubMed].
- Australian Bureau of Statistics. Autism in Australia 2012. 3 June 2014.
- Seida JC, Schouten JR, Boylan K, et al. Antipsychotics for children and young adults: a comparative effectiveness review. Pediatrics 2012;129:e771–84. [PubMed].
- Crossley NA, Constante M, McGuire P, et al. Efficacy of atypical v. typical antipsychotics in the treatment of early psychosis: meta-analysis. Br J Psychiatry 2010;196:434–9. [PubMed].
- Maayan L, Correll CU. Weight gain and metabolic risks associated with antipsychotic medications in children and adolescents. J Child Adolesc Psychopharmacol 2011;21:517–35. [PubMed].
- Lemmon ME, Gregas M, Jeste SS. Risperidone use in autism spectrum disorders: a retrospective review of a clinic-referred patient population. J Child Neurol 2011;26:428–32. [PubMed].
- Sharma A, Shaw SR. Efficacy of risperidone in managing maladaptive behaviors for children with autistic spectrum disorder: a meta-analysis. J Pediatr Health Care 2012;26:291–9. [PubMed].
- Arango C, Parellada M, Moreno DM. Clinical effectiveness of new generation antipsychotics in adolescent patients. Eur Neuropsychopharmacol 2004;14[Suppl 4]:S471–9. [PubMed].
- International Diabetes Federation. IDF worldwide definition of the metabolic syndrome. 2005. (accessed 5 September 2014).
- Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 2009;302:1765–73. [PubMed].
- Steinberger J, Moran A, Hong CP, et al. Adiposity in childhood predicts obesity and insulin resistance in young adulthood. J Pediatr 2001;138:469–73. [PubMed].
- Whitaker RC, Wright JA, Pepe MS, et al. Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med 1997;337:869–73. [PubMed].
- Government of South Australia Women’s and Children’s Health Network. Child Adolescent Mental Health Services (CAMHS) Procedure. Guidelines for Monitoring Adverse Effects in Children and Adolescents Prescribed Antipsychotic Medication. October 2011 (accessed 5 September 2014).
- Correll CU. Antipsychotic use in children and adolescents: minimizing adverse effects to maximize outcomes. J Am Acad Child Adolesc Psychiatry 2008;47:9–20.[PubMed].