Antipsychotics

Antipsychotics are prescription medicines used in the treatment of psychosis, prescribed most often in schizophrenia and other psychotic disorders. This page sets out what the major guidelines ask of prescribers, and what that means for anyone taking these medicines or deciding whether to.

What antipsychotics are, and what this page is for

Psychosis involves a change in the way reality is perceived, which can mean hearing or seeing things that are not there.²

It can also mean holding fixed beliefs despite evidence to the contrary. Stigma and discrimination against people living with schizophrenia are common.²

There are no doses here, and no one medicine is recommended over another.

What antipsychotics are prescribed for

The core use is schizophrenia and other psychotic disorders. The World Health Organization recommends offering oral antipsychotic medicines to adults living with a psychotic disorder,¹ and asks that the choice weigh benefit, side effects and the person's own preference.

Antipsychotics are prescribed in some other situations too; your prescriber is the person who can tell you why a particular medicine was chosen.

At least one in three people living with schizophrenia will fully recover.²

How they are thought to work

The mechanism is only partly understood. First-generation antipsychotics work by inhibiting dopamine signalling in the brain. Second-generation medicines block dopamine receptors and act on serotonin receptors too.³ Dopamine and serotonin are chemical messengers that nerve cells use to signal to each other.

These medicines act at receptors, which is not the same as returning a brain to a correct baseline.

First-generation and second-generation medicines

Antipsychotics are commonly grouped into first-generation and second-generation medicines, though the grouping is less informative than the names suggest.

Second-generation antipsychotics carry a lower risk of movement side effects. They are associated with significant weight gain and with metabolic syndrome.⁴ Metabolic syndrome is a group of changes in weight, blood pressure, blood sugar and blood fats.

Neither generation is simply better. The World Health Organization treats newer medicines as an alternative to older ones.¹ That holds where supply can be assured and cost is not a barrier.

Choosing one is a shared decision

The guidelines describe a joint decision.

In England and Wales, the National Institute for Health and Care Excellence, or NICE, is explicit about this. The choice of antipsychotic should be made by the person and the healthcare professional together.⁵ The carer's views are included if the person agrees.

The World Health Organization uses similar language. It asks prescribers to balance effectiveness, side effects and individual preference.¹

Side effects, named plainly

Antipsychotics have real side effects, and knowing them by name makes them easier to raise with a prescriber.

NICE asks prescribers to discuss the benefits and possible side effects of each medicine. It groups them into five families.⁵

A medicine can be effective by every measure and still feel intolerable to take, and it is a legitimate thing to raise with a prescriber.

What good monitoring looks like

Antipsychotics call for physical health monitoring, so knowing what that involves makes it easier to notice when it is not happening.

Before starting, NICE asks for baseline checks in England and Wales. These cover weight, waist circumference, pulse and blood pressure. They also cover blood glucose, a blood lipid profile, prolactin and an assessment of movement.⁵ Prolactin is a hormone measured in a blood sample.

Monitoring then continues. NICE asks for weight weekly over the first six weeks, then at twelve weeks and at one year.⁶ Yearly checks follow after that.

The secondary care team holds responsibility for at least the first twelve months,⁶ or until the person's condition has settled, whichever is longer.

NICE also frames a new medicine as an explicit individual therapeutic trial. That means the medicine is tried and assessed, not simply started. The side effects a person is most willing to tolerate are discussed and recorded at the start.⁶

Guidance differs between countries, so local practice may not match this. It still indicates what is reasonable to ask about.

When the first medicines do not help

Sometimes the first medicines tried do not help enough. The guidelines recognise this, and it does not mean nothing will work.

Where a psychotic disorder has not responded to other treatment, clozapine should be considered.¹ The World Health Organization asks that this happen under mental health specialist supervision.

Clozapine comes with a specific requirement. It can cause agranulocytosis and leukopenia, which are drops in white blood cell counts.⁷ Neutrophils are a type of white blood cell. That is why anyone taking clozapine has regular monitoring of white cells and neutrophils.

Antipsychotics and dementia: a narrow use

Antipsychotics are sometimes prescribed to people living with dementia who are distressed or agitated. The guidelines treat this use differently from the treatment of a psychotic disorder.

NICE guidance for England and Wales asks that psychosocial and environmental interventions come first.⁸ They are the initial and ongoing management. That means changes to daily routine, surroundings and support.

Antipsychotics are offered only in narrow circumstances. One is where a person is at risk of harming themselves or others. The other is where agitation, hallucinations or delusions cause severe distress.⁸

NICE notes that this is an off-label use for almost all antipsychotics.⁸ It points prescribers to advice from the Medicines and Healthcare products Regulatory Agency. Off-label means a medicine is used outside the conditions it was licensed for.

Where they are used, the guidance asks for the lowest effective dose and the shortest possible time. The person should be reassessed at least every six weeks.⁸

One group of dementias carries an added risk. In dementia with Lewy bodies and Parkinson's disease dementia, antipsychotics can worsen movement problems. They can also cause severe sensitivity reactions.⁸

These are fair questions for a family member to put to the prescriber.

Thinking about stopping, or wanting to change

Many people who take antipsychotics think about stopping, and that is not a failure of insight.

Stopping or changing an antipsychotic is a conversation with your prescriber; it is not a decision to take alone.

The reason is practical. NICE asks that people be told there is a high risk of relapse if medication is stopped. That risk applies to the next one to two years.⁹

Where medication is withdrawn, the guidance asks that it be done gradually, with regular monitoring for signs of relapse. Monitoring continues for at least two years afterwards.⁹

Coming off is a managed clinical process, and doing it abruptly and alone carries its own risk. If side effects are the reason for wanting to stop, saying so directly helps. That is a clinical problem with possible answers.

Where therapy and psychosocial support fit

Medication is not the whole of the care that helps: psychological and social support form part of the same plan.

For a first episode of psychosis, NICE asks that antipsychotic medication be offered together with psychological intervention. That means family intervention and individual cognitive behavioural therapy.¹⁰

The guidance also covers someone who wants to try psychological work alone. NICE asks that the person be advised these work better alongside medication.¹⁰

If they still wish to try, family intervention and CBT should be offered. A review of options is agreed within a month, with symptoms monitored.¹⁰

The World Health Organization lists a range of effective care options. These include psychoeducation, family interventions, cognitive behavioural therapy and psychosocial rehabilitation.¹¹ It calls for a recovery-oriented approach that gives people agency in treatment decisions. Psychoeducation means teaching people about the condition and its treatment.

One further recommendation concerns trauma. NICE asks clinicians to assess for post-traumatic stress and other reactions to trauma.¹² People living with psychosis are likely to have experienced previous adverse events.

Our guide on how to find the right therapist sets out what to look for when choosing someone to work with alongside medical care.

Access and availability around the world

Whether you can get these medicines depends a great deal on where you live. That is a fact about health systems, not about you.

The World Health Organization publishes a Model List of Essential Medicines. It includes a section for medicines used in psychotic disorders.¹³ Listed medicines are meant to be available in functioning health systems at all times.¹⁴

They are also meant to be affordable for people and health systems.¹⁴ Access does not match that standard. More than two out of three people living with psychosis receive no specialist mental health care.²

This is also why the World Health Organization frames newer medicines conditionally. They are an option where supply is reliable and cost is not a constraint.¹

Signs that need urgent medical attention

Side effects are usually something to raise at your next review. One reaction is different, and needs attention straight away.

Neuroleptic malignant syndrome is rare but potentially fatal.⁴ It can occur at any point during treatment.⁴ It involves raised temperature, severe muscle rigidity, confusion and agitation.⁴

If these develop together, treat it as a medical emergency. Go to your nearest emergency service or contact local emergency services. Our worldwide list of ambulance and emergency numbers may help.

For distress rather than physical danger, the worldwide helplines and crisis lines list is a place to start. TherapyRoute cannot offer real-time support and does not monitor messages.

Questions worth taking to your prescriber

All of this leads to one conversation with a prescriber. The questions below are prompts, not demands.

• What is this medicine meant to help with, and how will we know if it is working?
• Which side effects should I watch for, and which would you want to hear about quickly?
• Which side effects am I most willing to live with, and can we record that?
• What baseline checks will you do before I start?
• How will my physical health be monitored, and who is responsible for it?
• When will we review this, and what happens if it is not helping?
• If I ever want to come off, how would we go about it safely?

If a prescriber cannot answer these, that is useful information too.

This article is for general information and is not a substitute for professional assessment or care. If this is affecting your life, consider reaching out to a qualified mental health professional.

References

1. [1] World Health Organization. mhGAP Evidence Centre: Antipsychotic medicines for psychotic disorders (2023 updated). who.int.
2. [2] World Health Organization. Schizophrenia fact sheet: Key facts. who.int.
3. [3] Chokhawala K, Stevens L. Antipsychotic Medications. StatPearls Publishing. Mechanism of Action. ncbi.nlm.nih.gov/books/NBK519503.
4. [4] Chokhawala K, Stevens L. Antipsychotic Medications. StatPearls Publishing. Adverse Effects. ncbi.nlm.nih.gov/books/NBK519503.
5. [5] National Institute for Health and Care Excellence (NICE). CG178 Psychosis and schizophrenia in adults, recommendations 1.3.5.1 and 1.3.6.1 (England and Wales). nice.org.uk.
6. [6] National Institute for Health and Care Excellence (NICE). CG178 Psychosis and schizophrenia in adults, recommendations 1.3.6.3 to 1.3.6.5 (England and Wales). nice.org.uk.
7. [7] Chokhawala K, Stevens L. Antipsychotic Medications. StatPearls Publishing. Adverse Effects: clozapine and boxed warnings. ncbi.nlm.nih.gov/books/NBK519503.
8. [8] National Institute for Health and Care Excellence (NICE). NG97 Dementia, recommendations 1.7.2 to 1.7.8 (England and Wales). nice.org.uk.
9. [9] National Institute for Health and Care Excellence (NICE). CG178 Psychosis and schizophrenia in adults, recommendations 1.4.6.3 to 1.4.6.5 (England and Wales). nice.org.uk.
10. [10] National Institute for Health and Care Excellence (NICE). CG178 Psychosis and schizophrenia in adults, recommendations 1.3.4.1 and 1.3.4.2 (England and Wales). nice.org.uk.
11. [11] World Health Organization. Schizophrenia fact sheet: Services, management and support. who.int.
12. [12] National Institute for Health and Care Excellence (NICE). CG178 Psychosis and schizophrenia in adults, recommendations 1.3.3.1 and 1.3.3.3 (England and Wales). nice.org.uk.
13. [13] World Health Organization. WHO Model List of Essential Medicines, 23rd List (2023), section 24.1 Medicines for psychotic disorders. iris.who.int.
14. [14] World Health Organization. WHO Model List of Essential Medicines, 23rd List (2023): overview. who.int.