Metabolic and Cardiovascular Adverse Events Associated With Antipsychotic Treatment in Children and Adolescents

Department of Psychiatry and Pharmacology, Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
JAMA Pediatrics (Impact Factor: 5.73). 11/2008; 162(10):929-35. DOI: 10.1001/archpedi.162.10.929
Source: PubMed


To identify factors associated with incident cardiovascular events and metabolic disturbance in children and adolescents treated with antipsychotics.
A retrospective cohort design evaluating Medicaid medical and pharmacy claims.
South Carolina's Medicaid program covering outpatient and inpatient medical services and medication prescriptions from January 1, 1996, through December 31, 2005.
A treatment cohort of 4140 children and adolescents prescribed 1 of 5 atypical or 2 conventional antipsychotics, and a random sample of 4500 children not treated with psychotropic medications. Main Exposure Antipsychotics.
Incidence/prevalence rates for obesity, type 2 diabetes mellitus, dyslipidemia, cardiovascular events, cerebrovascular events, hypertension, and orthostatic hypotension.
Compared with the control sample, the treated cohort had a higher prevalence of obesity (odds ratio [OR], 2.13), type 2 diabetes mellitus (OR, 3.23), cardiovascular conditions (OR, 2.70), and orthostatic hypotension (OR, 1.64). In the treated cohort, patients exposed to multiple antipsychotics were at significantly higher risk for incident obesity/weight gain (OR, 2.28), type 2 diabetes mellitus (OR, 2.36), and dyslipidemia (OR, 5.26). Incident cardiovascular events were more likely with the use of conventional (OR, 4.34) or multiple (OR, 1.57) antipsychotics and mood stabilizers (OR, 1.31). Incident orthostatic hypotension was more prevalent in those coprescribed selective serotonin reuptake inhibitors (OR, 1.77) and mood stabilizers (OR, 1.35).
Antipsychotics are associated with several metabolic and cardiovascular-related adverse events in pediatric populations, especially when multiple antipsychotics or classes of psychotropic medications are coprescribed, controlling for individual risk factors.

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Available from: Jeanette M Jerrell, Oct 16, 2014
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    • "Dyslipidaemia. McIntyre and Jerrell (2008) and Jerrell et al. (2008) "
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    ABSTRACT: Aims: We aim to identify the prevalence and management strategies of nine clinically important categories of antipsychotic adverse effects, namely: extrapyramidal symptoms; sedation; weight gain; type II diabetes; hyperprolactinaemia; metabolic syndrome, dyslipidaemia; sexual dysfunction; and cardiovascular effects. Background: Antipsychotic drugs are widely prescribed for schizophrenia and other mental disorders. The adverse effects of antipsychotics are common, with a potential negative impact on adherence and engagement. Despite this, the scientific study of the prevalence or management of adverse antipsychotic effects is a neglected area. Method: A systematic review was undertaken using pre-defined search criteria and three databases, with hand searching of citations and references. Inclusion was agreed on by two independent researchers after review of abstracts or full text. Quality analysis of included studies was conducted using pre-agreed criteria. Results: In total, 53 studies met inclusion criteria, revealing the following: (1) antipsychotic polypharmacy was associated with increased frequency of adverse effects, and (2) a longer duration of treatment is associated with greater severity (e.g. higher BMI); (3) clozapine was more strongly associated with metabolic disturbance than other antipsychotics in three studies and olanzapine was associated with the most weight gain in three studies; (4) hyperprolactinaemia was more common in women than men, but 50% men noted sexual dysfunction versus 25–50% in women; (5) despite clinical guideline recommendations there is a low rate of baseline testing for lipids and glucose; and (6) seven studies described adverse effect management strategies, but only two examined their efficacy – one found a significant reduction in weight with non-pharmacological group therapy and the other found a significant reduction in dyslipidaemia with statins. Conclusions: Antipsychotic adverse effects are diverse and frequently experienced, but are not often systematically assessed. There is a need for further scientific study concerning the management of these side effects.
    Journal of Psychopharmacology 12/2014; 1(4). DOI:10.1177/0269881114562090 · 3.59 Impact Factor
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    • "Unfortunately, all are associated with significant adverse effects (Kowatch et al. 2005, 2009). A medical claim study found higher rates of a variety of adverse cardiometabolic effects in > 4000 youth who had been prescribed an atypical antipsychotic or one of two conventional antipsychotics, than in a random sample of 4500 youth not treated with psychotropics (McIntyre and Jerrell 2008). An open-label study of second-generation antipsychotic treatment in inpatient youth with various psychiatric diagnoses showed weight gain with all (including aripiprazole, olanzapine, quetiapine, and risperidone), after 12 weeks, compared with youth who had received no treatment. "
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    ABSTRACT: Objective: The purpose of this study was to report the safety, tolerability, and serum micronutrient concentrations and their correlations with mood changes from an 8 week pilot feasibility study of a 36 ingredient multinutrient supplement, EMPowerplus (EMP+), for pediatric bipolar spectrum disorders (BPSD). Methods: Ten children ages 6-12 received EMP+ escalating from one to four capsules t.i.d., with four children increased to the maximum suggested dose, five capsules t.i.d. Outcome measures were micronutrient concentrations in serum and red blood cells, vital signs, body mass index (BMI), dietary intake (Food Frequency Questionnaire and 24 hour dietary recall interview), and mood and global functioning ratings. Results: Seven children (70%) completed the study. Three (30%) terminated early for tolerability and compliance issues. Adverse effects were mild and transient, and chiefly consisted of initial insomnia or gastrointestinal (GI) upset. No differences occurred in BMI (p = 0.310) or waist-hip ratio (WHR; p = 0.674) pre- to postsupplementation. Four of the tested serum vitamin concentrations increased from pre- to postsupplementation: vitamin A-retinol, vitamin B6, vitamin E-α-tocopherol; and folate (all p<0.05). The increase in serum 25-OH vitamin D approached significance (p = 0.063). No differences were found in dietary intake pre- to postsupplementation, suggesting that blood nutrient level increases were caused by EMP+. Conclusions: In this open prospective study, short-term use of EMP+ in children with BPSD appeared safe and well-tolerated, with a side effect profile preferable to first-line psychotropic drugs for pediatric bipolar spectrum disorders. A double-blind, randomized clinical trial is feasible, appears safe, and is warranted by open-label clinical outcomes and plausible mechanisms of action, combined with documentation of increased serum concentrations of specific micronutrients.
    Journal of child and adolescent psychopharmacology 10/2013; 23(8):558-67. DOI:10.1089/cap.2012.0098 · 2.93 Impact Factor
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    • "On the other hand, a possible synergistic interaction between age and polytherapy (McIntyre & Jerrell, 2008) seems to emerge from the analysis of recent retrospective and prospective clinical reports. Besides corroborating the elevated probability of metabolic syndrome in patients medicated with AAPs, this study (McIntyre & Jerrell, 2008) also highlighted the strong positive association between younger age, polytherapy and higher risk for obesity, type 2 diabetes and CV disease. Regarding the predictive value of the initial age of treatment, two recent prospective studies consistently showed the higher magnitude of body weight increase in children and adolescents underwent to OL, CLZ and RIS therapy as compared to adult population (Fleischhaker et al., 2007, 2008). "
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    ABSTRACT: Beside the therapeutic improvement over first-generation antipsychotics, the fact that prescription of atypical agents is also associated to the emergence of severe metabolic derangement in patients is not a mystery anymore. Body weight gain, dyslipidemia, adiposity, impaired glucose homeostasis, insulin and leptin resistance and new-onset type II diabetes are all part of a syndromic cluster of vast medical concern. Thus, clinical reports and rodent models of atypical antipsychotic-associated metabolic impairment have growth in parallel as separate territories. This review focuses on the attempt to take a snapshot of the present developing moment and to describe to what extent clinical data are reflected by the findings derived from animal studies. This aim is pursued through different steps that, starting from the criteria necessary to characterize the "atypicality" of atypical drugs, then explore the consistency among clinical and animal-based data. The endpoint of this survey consists in the analysis of the potential mechanisms underlying the metabolic derangement induced by this class of drugs. It is, indeed, our opinion that some atypical antipsychotics should be viewed as potent obesogenic factors that can be exploited as valuable tools to shed light into the elusive dilemma of obesity. For this reason, recently identified obesogenic and diabetogenic mechanisms are the background on which the present work is built and some novel forthcoming lines of investigation suggested.
    Pharmacology [?] Therapeutics 09/2010; 127(3):210-51. DOI:10.1016/j.pharmthera.2010.04.008 · 9.72 Impact Factor
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