Atypical (second-generation) antipsychotics

Reminder to monitor and manage weight, glucose, and lipid levels.

Article date: April 2011

People with schizophrenia are three times more likely to die prematurely from natural causes (mainly cardiovascular disease) compared with people without mental health disorders[footnote 1] [footnote 2]. Schizophrenia also seems to be associated with modifiable and non-modifiable risk factors for cardiovascular morbidity and mortality (eg, smoking, poor diet, sedentary lifestyle, and family history of cardiovascular disease).

Some atypical (second-generation) antipsychotics are associated with significant weight gain (>7% of baseline), dyslipidaemia, and hyperglycaemia (metabolic adverse effects). Individual atypical antipsychotics differ in their propensity for metabolic adverse effects: available data suggest that clozapine, olanzapine, and quetiapine are especially implicated[footnote 3].

An analysis of baseline data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study confirms that people with schizophrenia are undertreated for metabolic disorders[footnote 4]. Given that people with schizophrenia are at an increased baseline risk of cardiovascular morbidity and mortality, the following are needed during atypical antipsychotic treatment to support the physical health of the patient in the long term:

  • early identification of modifiable risk factors
  • monitoring for further development of metabolic adverse effects
  • management of metabolic adverse effects

Although the available data do not support a similar association between typical (first-generation) antipsychotics and metabolic adverse effects, the increased risk associated with schizophrenia means that the physical wellbeing of all patients should be assessed, monitored and treated according to relevant clinical guidelines.

NICE guidance on schizophrenia[footnote 5] gives further information about physical health screening for people with schizophrenia (see Chapter 9, sections –

NICE guidance

GPs and primary healthcare professionals should monitor the physical health of people with schizophrenia at least once a year. Focus on cardiovascular disease risk assessment as described in NICE clinical guideline 67—lipid modification[footnote 6], but bear in mind that people with schizophrenia are at a higher risk of cardiovascular disease than the general population.

People with schizophrenia at increased risk of developing cardiovascular disease and/or diabetes (eg, those with elevated blood pressure, raised lipid levels, smokers, increased waist measurement) should be identified at the earliest opportunity; their care should be managed using the appropriate NICE guidance for prevention of these conditions [footnote 7] [footnote 8] [footnote 9]

Treat people with schizophrenia who have diabetes and/or cardiovascular disease in primary care according to the appropriate NICE guidance.

Further advice

Encourage and educate patients as appropriate to maintain a healthy diet and regular exercise

Any decision to change antipsychotic drugs should be based on a careful assessment of the potential benefits and on the risks of destabilising their mental state.

Further information

Metabolic and lifestyle issues and severe mental illness—new connections to well-being? Expert Consensus Meeting, Dublin, 14–15 April 2005, consensus summary. Journal Psychopharmacol 2005; 19 (suppl 6): 118–22.

Foley DL and Morely KI. Systematic review of early cardiometabolic outcomes of the first treated episode of psychosis. Arch Gen Psychiatry, published online Feb 7, 2011. doi:10.1001/archgenpsychiatry.2011.2

Mackin P and Thomas SHL. Atypical antipsychotic drugs. BMJ 2011; 342: d1126.

Summaries of product characteristics and patient information leaflets for atypical antipsychotics are available via the Electronic Medicines Compendium (external link)

BNF section 4.2.1 Antipsychotic drugs

Article citation: Drug Safety Update April 2011; vol 4 issue 9: H1

  1. Brown S, et al. Br J Psychiatry 2010; 196: 116–21 

  2. Hennekens CH. J Clin Psychiatry 2007; 68: 4–7 

  3. Rummel-Kluge C, et al. Schizophr Res 2010; 123: 225–33 

  4. Nasrallah HA, et al. Schizophr Res 2006; 86: 15–22 

  5. National Institute for Health and Clinical Excellence. Core interventions in the treatment and management of schizophrenia in primary and secondary care (update). Clinical guideline 82. 2009 

  6. National Institute for Health and Clinical Excellence. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Clinical guideline 67. 2008

  7. National Institute for Health and Clinical Excellence. Type 1 diabetes: diagnosis and management of type I diabetes in children, young people and adults. Clinical guideline 15. 2004

  8. National Institute for Health and Clinical Excellence. Type 2 diabetes: the management of type 2 diabetes (update). Clinical guideline 66. 2008

  9. National Institute for Health and Clinical Excellence. Obesity: guidance on the prevention identification, assessment and management of overweight and obesity in adults and children. Clinical guideline 43. 2006

Published 11 December 2014