Guidance

Antipsychotic medicines

Published 25 August 2005

1. Overview

Antipsychotic medicines are mainly used to treat mental health conditions such as schizophrenia and other psychoses, agitation, severe anxiety, mania and violent or dangerously impulsive behaviour.

They are also used to treat nausea and vomiting, intractable hiccough and for the management of pain and associated restlessness in palliative care.

2. How antipsychotic medicines work

Antipsychotics work by increasing or reducing the effects of natural chemicals (called neurotransmitters) in the brain, including:

• Dopamine
• Serotonin
• Noradrenaline
• acetylcholine

These neurotransmitters regulate numerous aspects of behaviour including:

• mood and emotions
• control of sleeping and wakefulness
• control of feeding

Antipsychotics can be classified by their chemical structure, but can also be distinguished by their pharmacology (their action at different neurotransmitters receptors) and by their clinical properties.

Older antipsychotics were first developed in the 1950s and act primarily to reduce the effect of dopamine in the brain.

Newer antipsychotics were developed from the 1970s onwards. The newer antipsychotics are less likely to cause movement disorders as a side effect than older antipsychotics, although they may still cause movement disorders when used at higher doses.

The following newer antipsychotics are licensed for use in the UK:

• amisulpride (brand name Solian)
• aripiprazole (Abilify)
• clozapine (Clozaril, Denzapine, Zaponex)
• lurasidone (Latuda)
• olanzapine (Zypadhera, Zyprexa)
• paliperidone (Invega, Xeplion)
• quetiapine (Seroquel, Seroquel XL)
• risperidone (Risperdal, Risperdal Consta)

Older antipsychotics licensed for use in the UK include:

• chlorpromazine
• flupentixol
• haloperidol
• levomepromazine
• pericyazine
• perphenazine
• pimozide
• prochlorperazine
• promazine
• sulpiride
• trifluperazine
• zuclopenthixol

3. Side effects of antipsychotic drugs

As with all medicines, antipsychotics can produce side effects in some people.

The most common include movement disorders (referred to as extrapyramidal side effects) such as:

• akathisia (an unpleasant feeling of restlessness with involuntary body movements) or dystonia (abnormal muscle contractions)
• dry mouth
• blurred vision and constipation (often called ‘anticholinergic effects’ because they result from blockade of cholinergic receptors)
• dizziness or light headedness
• weight gain

Rarely, antipsychotics may cause more serious side effects such as:

• changes to blood sugar levels or blood lipid levels
• neuroleptic malignant syndrome:
  • fever
  • faster breathing
  • sweating
  • muscle stiffness
  • reduced consciousness
• cardiac arrhythmias (irregular heart beat)

A Europe-wide review of effects of antipsychotics on the heart was completed in 2005.

Antipsychotics can also increase the risk of stroke in elderly people with dementia and in any patient with pre-existing risk factors for stroke.

This is not a complete list of all of the known side effects of antipsychotics - full guidance on prescribing and use, including information on possible side effects of antipsychotics is provided in the summary of product characteristics (SPC) for health professionals and the patient information leaflet (PIL) that should accompany the medicine for patients.

Further guidance can be found on the electronic Medicines Compendium website.

4. Antipsychotic use in elderly people with dementia

There is a clear increased risk of stroke and a small increased risk of death when antipsychotics are used in elderly people with dementia.

Only 1 antipsychotic, risperidone (Risperdal), is licensed for treatment of dementia-related behavioural disturbances in the UK and then only specifically for short-term (up to 6 weeks) treatment of persistent aggression in moderate to severe Alzheimer’s dementia which is unresponsive to non-pharmacological approaches (ie those that do not involve use of medicines) and where there is risk of harm to the patient or others.

The risperidone (Risperdal) licence for the short-term treatment of persistent aggression in Alzheimer’s dementia was granted in 2008. This followed a new analysis of 3 randomised controlled trials ^{[footnote 1]}, ^{[footnote 2]}, ^{[footnote 3]} conducted on behavioural problems in the elderly showed a clear benefit for the short-term use of risperidone when aggression only was considered.

4.1 Increased risk of stroke

In 2004, the Committee on Safety of Medicines (the predecessor to the Commission on Human Medicines) advised of a clear increase in the risk of stroke with the use of the antipsychotics risperidone or olanzapine in elderly people with dementia. (The risk was approximately three-fold increased risk compared with the placebo).

The committee advised that the magnitude of risk outweighed any likely benefit of treating dementia-related behavioural problems with these drugs.

This increased risk is also a cause for concern in any patient with a high baseline risk of stroke. A year later, a Europe-wide review of the risk of cerebrovascular accidents (CVA), in particular when used in dementia patients concluded that this risk could not be excluded for other antipsychotics (atypical or typical).

4.2 Increased mortality

In 2005, an analysis of 17 placebo-controlled trials found that newer antipsychotics are associated with increased mortality when used in elderly people with dementia (about 1-2% increased risk compared with no treatment).

For risperidone, there is an additional increase in the risk when co-prescribed with furosemide.

In November 2008, a European assessment of published observation data concluded that a similar increased risk of death could not be excluded for the older antipsychotics ^{[footnote 4]}, ^{[footnote 5]}.

5. Further reading

European Medicines Agency (EMA): Risperdal

Committee for Medicinal Products for Human Use (CHMP) assessment report on conventional antipsychotics

EMA: questions and answers on the review of the use of conventional antipsychotic medicines in elderly patients with dementia

MHRA Public Assessment Report: The risk of venous thromboembolism associated with antipsychotics

1. Katz IR, et al. J Clin Psychiatry 1999; 60: 107–15. ↩

2. De Deyn PP, et al. Neurology 1999; 53: 946–55. ↩

3. Brodaty H, et al. J Clin Psychiatry 2003; 64: 134–43. ↩

4. Schneeweiss S, et al. CAMJ 2007; 176: 627–32. ↩

5. Gill SS, et al. Ann Intern Med 2007; 146: 775–86. ↩