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3.4 Metabolic adverse effects

Metabolic effects Many antipsychotics are associated with weight gain, dyslipidaemia, hyperglycaemia and diabetes mellitus; these are also characteristics features of the metabolic syndrome1. These effects increase the risk of adverse cardiovascular events and of early death.

Weight gain occurs most frequently during 6–12 months of starting antipsychotic treatment.

Antipsychotics vary in their risk for metabolic effects and weight gain, but the evidence is strongest for an association with second-generation antipsychotics, especially clozapine, olanzapine, and quetiapine. Schizophrenia2 is itself associated with an increased risk of insulin-resistant diabetes and cardiovascular disorders.

Factors which increase risk

Risk factors that may predispose patients to metabolic complications include obesity and personal or family history of diabetes, hyperlipidaemia, hypercholestrolaemia, thyroid disorder and pituitary adenoma.

Left untreated, hyperglycaemia can progress to ketoacidosis3, coma and death.

The metabolic effects of antipsychotics might also be augmented by medicines with similar effects, such as corticosteroids4 (which can increase the risk of weight gain and diabetes).

Risk-reduction measure

Biochemical and clinical assessment at the start of treatment can identify those at greater risk of lipid disorders and hyperglycaemia; in such patients antipsychotics associated with a higher risk of metabolic effects are best avoided.

Modifiable risk factors for cardiovascular diseases (eg smoking, diet, excessive alcohol consumption, lack of exercise) should be addressed.

Monitoring during treatment allows prompt identification of adverse metabolic effects. Risk-reduction measures include advising patients and carers to watch out for features such as unusual thirst, increased urine output, unexplained weight changes, and weakness.

If a patient’s weight increases by over 2 kg in the first two weeks and the antipsychotic cannot easily be switched then strict dietary control should be considered.


If the antipsychotic cannot be withdrawn or treatment switched to a drug with lower risk of metabolic effects, then specific treatment should be instituted to manage the metabolic effects. Such treatment might include non-pharmacological and pharmacological measures against weight gain, hyperglycaemia and dyslipidaemia.

This learning module discusses noteworthy risks for antipsychotics. Summaries of product characteristics and the BNF should be consulted for a fuller account of the adverse effects and warnings for individual antipsychotics.

  1. Features of the metabolic syndrome include central obesity, together with two of: raised triglycerides, reduced HDL-cholesterol, raised blood pressure and raised fasting plasma glucose (or previously diagnosed type 2 diabetes)
  2. A mental disorder which affects how the individual feels, behaves and thinks
  3. Presence in the blood of ketones, which are toxic byproducts of fat metabolism; fat is metabolised instead of glucose in patients with insulin deficit (diabetes)
  4. Substances that mimic effects of hormones produced by the adrenal cortex. The term corticosteroids covers glucocorticoids (steroids which reduce inflammation) and mineralocorticoids (steroids which act on the kidneys to retain sodium and water and promote excretion of potassium)