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  • In adults with intellectual disability, discontinuation of antipsychotics is associated with reduction in weight, BMI, waist circumference and blood pressure

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Care of people with learning disabilities
Cohort study
In adults with intellectual disability, discontinuation of antipsychotics is associated with reduction in weight, BMI, waist circumference and blood pressure
  1. Pierre Chue
  1. Department of Psychiatry, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada
  1. Correspondence to : Professor Pierre Chue, Department of Psychiatry, Faculty of Medicine, University of Alberta, 9942-108 Street, Edmonton, Alberta, Canada T5K 2J5; pchue{at}ualberta.ca

https://doi.org/10.1136/eb-2013-101548

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    Commentary on: de Kuijper G, Mulder H, Evenhuis H, et al. Effects of controlled discontinuation of long-term used antipsychotics on weight and metabolic parameters in individuals with intellectual disability. J Clin Psychopharmacol 2013;33:520–4.OpenUrlCrossRefPubMed

    Implications for practice and research

    • Improvement in metabolic parameters can occur after discontinuation or dose reduction of antipsychotics.

    • Discontinuation of antipsychotics does not result in worsening of behaviours in the majority of patients.

    • Patients should be regularly reviewed with respect to the appropriateness of current antipsychotic regimens.

    Context

    The prevalence of psychotropic drug use, particularly antipsychotics in patients with intellectual disability (ID), is high. The use of such agents for behavioural control frequently represents off-label use and is not supported by current guidelines.1 Certain psychiatric populations are very susceptible to metabolic disruption by antipsychotics, due to age, ethnicity, genetic and disease factors. Metabolic syndrome is reported in up to 45% of patients with ID.2 Patients with ID have a shorter life expectancy and elevated risk of early death when compared with the general population, yet monitoring remains poor.3 Current research into pharmacogenetics has identified genetic polymorphisms that appear to be associated with increased risk of metabolic adverse events.

    Methods

    De Kuijper and colleagues examined the effects of a controlled discontinuation of long-term antipsychotics on metabolic parameters in an ID population (n=99). They also evaluated the relationship to the use of atypical antipsychotics, and the presence of a genetic polymorphism of the 5HT2C receptor gene (rs1414334) known to be associated with metabolic disturbance. Other psychiatric comorbidity was permitted but not schizophrenia or major affective disorder. The majority of patients (78%) were on typical antipsychotics and none were on atypical antipsychotics known to be less metabolically disruptive, such as ziprasidone or aripiprazole. Concomitant psychotropic medication use was not recorded nor was use of any psychotropic medications that patients might receive to replace the antipsychotic. Further, patients could be put back on antipsychotics after evaluation, and at least seven patients required re-instigation of an antipsychotic. It is not reported whether this was the same agent as previously prescribed. Not reported were treatment history, duration on prior antipsychotic, family history of obesity, diabetes or cardiovascular disease and smoking status—all of which are potential confounding factors. The number of patients with the rs1414334 allele was not clearly identified.

    Findings

    Twelve weeks after discontinuation, a third of patients were no longer taking antipsychotics, and there were substantial dose reductions among those that did not discontinue use completely. Antipsychotic discontinuation resulted in improvement in metabolic parameters even in those patients with dose reduction (with the exception of fasting plasma glucose). Complete discontinuation of antipsychotics was associated with the greatest decreases in waist circumference and body mass index. The presence of the rs141334 allele was predictive of greater metabolic disturbance.

    Commentary

    This was a unique and adventurous study. Switching to a less metabolically disruptive antipsychotic has been shown to improve metabolic parameters.4 However, discontinuation of antipsychotic medications particularly in an ID population is not a strategy that is often supported by staff, despite the lack of evidence base for the use of such agents for behavioural control and the clear susceptibility of patients with ID to an array of metabolic and neurological side effects.5 The improvement in metabolic outcomes coupled with the success of this approach has clear and important implications for clinical practice. As a clinician who has recently inherited a large practice of patients with ID, these data are extremely helpful in supporting a rationalisation of medication and consequent emphasis on behavioural assessment and non-pharmacological interventions. The role of pharmacogenetics in predicting response and adverse effects to medications represents an important avenue of research and may be particularly relevant for patients with ID. However, current technical and financial limitations prevent this from being a common tool to guide treatment decisions in clinical practice.

    References

    1. ↵
      American Psychiatric Association. Choosing wisely. http://www.psychiatry.org/choosingwisely
    2. ↵
      1. de Winter CF,
      2. Hermans H,
      3. Evenhuis HM,
      4. et al
      . Associations of symptoms of anxiety and depression with diabetes and cardiovascular risk factors in older people with intellectual disability. J Intellect Disabil Res 2013. doi:10.1111/jir.12049
    3. ↵
      1. Teeluckdharry S,
      2. Sharma S,
      3. O'Rourke E,
      4. et al
      . Monitoring metabolic side effects of atypical antipsychotics in people with an intellectual disability. J Intellect Disabil Res Published Online First 20 Apr 2013. doi:10.1111/jir.12049.
    4. ↵
      1. Chue P,
      2. Mandel F,
      3. Therrien F
      . The effect of ziprasidone on metabolic syndrome risk factors in subjects with schizophrenia: a 1-year, open-label, prospective study. In press.
    5. ↵
      1. de Kuijper G,
      2. Mulder H,
      3. Evenhuis H,
      4. et al
      . Determinants of physical health parameters in individuals with intellectual disability who use long-term antipsychotics. Res Dev Disabil 2013;34:2799–809.
      OpenUrlCrossRefPubMed

    Footnotes

    • Competing interests None.