Antipsychotics

They are a range of medications that are used for some types of mental distress or disorder - mainly schizophrenia ¹ and bipolar disorder ² (sometimes called manic depression). They can also be used to help anxiety or depression ³ where it is severe or difficult to treat.

Antipsychotic medicines can help to reduce symptoms such as:

• The experience of hearing voices that no-one else can hear (auditory hallucinations).
• Ideas that don't seem to be based in reality (delusions), which can be distressing and distracting
• Difficulty in thinking clearly and logically (thought disorder).
• The marked mood swings of bipolar disorder.
• Depression that is severe or difficult to treat

Some people with schizophrenia don’t seem to show their feelings, have poor motivation and a lack of interest in social activities or even caring for themselves (‘negative’ symptoms).

Antipsychotic medicines tend to be less helpful in the treatment of these problems ⁴.

All of these medicines affect the action of one or more chemicals in the brain called ‘neurotransmitters’ – these are the chemicals which brain cells need to communicate with each other. Dopamine is the main neurotransmitter affected by these medications. Among other things, it is involved in how we:

• Know that something is significant, important or interesting;
• Experience pleasure and reward
• Feel motivated.

It is also involved in the control of our muscles and movement.

If parts of the dopamine system in the brain become overactive, this seems to play a part in producing hallucinations, delusions and thought disorder (sometimes called ‘psychotic symptoms’).

Antipsychotic medicines help people to be less troubled by such problems. The aim is to find a dose of medication that is helpful without making the person feel too sleepy or 'drugged up'. 

Most antipsychotic medicines seem to treat psychotic symptoms equally well ⁵.

Even so, individuals react differently to them, particularly regarding their experience of side-effects.

It is difficult to predict how well a particular person’s illness will respond to a particular antipsychotic medicine.

An open ‘trial and error’ approach by the prescriber and the patient may be necessary to find the medicine that suits them best, and this may take some time. 

Antipsychotic medicines vary in their side effects ⁵. The aim is to try to choose a medicine that is safest for a particular patient, with side effects that are the most acceptable to them.

Antipsychotic medicines can be given in different ways: as tablets, capsules or liquid to be given by mouth once or more daily or as long-acting injections (‘depot’ or ‘long-acting injectable’ antipsychotic medication) that usually only need to be given every few weeks. 

Commonly-used oral antipsychotic medicines

Possible side effects 

The side effects of antipsychotic medication vary in nature and severity between medicines and from person to person.

Some of the more common and distressing or disabling side effects are as follows ⁶:

• Low blood pressure, sometimes associated with dizziness on standing quickly
• Feeling sleepy during the day
• Putting on weight
• An increased chance of developing diabetes.
• Dry mouth
• Constipation
• Stiffness and shakiness (called ‘parkinsonism’ because these symptoms resemble Parkinson’s disease)
• Feeling sluggish and slow in your thinking or finding it hard to concentrate
• Uncomfortable restlessness (akathisia)
• Irregular periods
• Breast swelling or tenderness.
• Interference with your sex life
• Involuntary movements, usually of the mouth, tongue and jaw and, less commonly, of the trunk, arms or legs (tardive dyskinesia): usually only seen in the elderly and/or with long-term treatment.
  

When a person is prescribed antipsychotic medication, they should be given a leaflet containing information about side effects at the same time.

The text in these leaflets can sometimes be rather too small to read easily and they are not always written in a way that is easy to understand. If you have questions about this kind of medication or would like more information, talk to a doctor, pharmacist or psychiatric nurse.

You may also be able to find information about these medicines on the website of your local mental health Trust.

The word ‘depot’ means that the medication is not taken as a tablet but as a long-acting injection (usually given every 2 to 4 weeks). The medication is slowly released in the body over this time. The effects are generally the same as medications taken by mouth. 

What's good about having a depot injection?

The person prescribed a depot will be seen by a member of their healthcare team, usually a nurse, every few weeks when they give the injection. So the person will have the opportunity to report to them any problems with the medication or raise any other concerns they wish to talk about.

Once the depot injection has been given there is no need to think about antipsychotic medication until the next injection is due. Compared with people who need to remember to take tablets every day, those on regular depot injections will have a more stable illness and be less likely to need to come into hospital ⁷.

What's not so good about having depot injections?

After the injection, some people experience discomfort at the injection site for a short while.

It takes a long time to know the effect of changing the dose. If the dose is increased or decreased neither the doctor nor the person receiving the injections will be sure what the effect of the change is for several weeks or months – it can take several injections before the full effects are seen

How are the injections given?

A nurse will give the injection. There is usually no-one else in the room except the person receiving the injection and the nurse. If the person is not happy with the injection site being used, they should let their nurse or doctor know, as it may be possible to change this.

For some depot antipsychotic medicines, the first injection is a small dose, to check that the medicine suits the person. If there are no problems then, a week or so later, regular injections at a standard dose can be started.

After each injection, the medicine will stay in your body for several weeks. The interval between injections is usually between 2 and 4 weeks.

Some of the common depot antipsychotic medicines ⁶

Clozapine is the only medicine that has been shown to help people with schizophrenia when their illness has not responded to treatment with other antipsychotic medicines¹.

It is usually only used after two or more antipsychotic medicines have been tried and found not to be helpful. Once it is clear that the illness has not done well with standard antipsychotic medication, the sooner treatment with clozapine is started the better the chance of it being really helpful ⁸.

Clozapine has many of the same side-effects as other antipsychotic medicines.

However, it seems to have very little, if any, effect on the dopamine systems which control movement, and so causes hardly any of the stiffness, shakiness, slowness or restlessness that you can get with other antipsychotic medicines.

It also does not seem to produce the longer-term problem of tardive dyskinesia and can actually be used to relieve this in some people.

The main drawback is that it can affect the bone marrow, leading to a shortage of white cells in the blood. This makes the person being treated with clozapine vulnerable to infection, which can be life-threatening.

If the number of white cells drops too far, the medication is stopped at once so that the bone marrow can recover. So everybody prescribed clozapine needs to have weekly blood tests for the first 18 weeks of treatment and then 2-weekly blood tests up to one year. After that, the tests are monthly ⁹.

Clozapine can also cause particular bothersome side effects, including pooling of saliva in the mouth, weight gain, severe constipation, a fast heart beat and, very occasionally, potentially serious effects on the heart. 

Although clozapine can be a difficult medicine to use and can have serious side effects, for most of the people starting this medicine the benefits, including a better quality of life, outweigh the problems. 

Schizophrenia

For the vast majority of people having their first episode of schizophrenia, the symptoms of the illness will be very much reduced by antipsychotic medication ¹⁰. The person will usually need to stay on this medication for a while to keep control of the symptoms .

People who have had more than one episode of illness may find that, despite staying on their medication, symptoms will sometimes return and may need to be treated in hospital. However, such worsening of the illness will occur much less often and be less severe if the prescribed medication is taken regularly ^1,10,11 .

Mood disorder

For those people with bipolar disorder, certain antipsychotic medications can be helpful during episodes of elevated mood and increased activity (hypomania) and periods of low mood and loss of interest in things (depression)². 

Continuing to take the medicines that helped during an episode of illness is usually the best way to avoid having further episodes and so stay well ².

Not everyone with a bipolar illness will need an antipsychotic medicine but if these medicines clearly improve the symptoms in an episode of illness, then the doctor may recommend that the person continues to take them. This is particularly likely to be the case if the illness has not improved with lithium treatment in the past or if the person cannot take lithium because of its side effects.

For people with depression, antipsychotic medication can sometimes work when an episode of illness is proving very difficult to treat or if the illness keeps returning ³.

Not everyone with depression will need to take antipsychotic medication. If this medication has helped recovery from an episode of illness, the doctor may recommend that the person continues to take it, to increase their chances of staying well.

If someone taking antipsychotic medication is thinking about stopping, it is important to consider what happened during previous episodes of illness.

The risk of the same symptoms and disturbances occurring again needs to be weighed up against not having the side effects of the medication.

The prescribing doctor can talk these things through with the person and help them come to the best decision.

For people with schizophrenia who have had more than one episode of illness, stopping antipsychotic medicine more than doubles the risk of becoming unwell again and needing to go into hospital ^11,12.

If a doctor advises a person to continue to take antipsychotic medication but they are reluctant to do so, they should try to list, with their doctor, all the feelings, thoughts and behaviours that might be indications that the illness is returning or getting worse.

These are called early warning or relapse signs and symptoms. Recognising these may help a person get help and treatment in a more timely way if they start to become unwell again.

If someone decides they may want to reduce, or stop taking antipsychotic medication, it should always be done under the advice of, and with support from,  a doctor. It is important that they stay in contact with their doctor or mental health worker, even if they have been well for a few weeks or months without medication.

Antipsychotics are not addictive, but your body does get used to them and stopping suddenly may make you feel physically and/or mentally unwell. So it best to reduce the dose of the medication slowly, giving each reduction a few weeks to take effect. 

If your symptoms do return or start to get worse while you are reducing the dose or after you have stopped completely, you should see your doctor to discuss your continued care and treatment plan.

The evidence is very clear that nothing else works as well as antipsychotic medications in the treatment of the more troublesome symptoms of schizophrenia and some other serious illnesses. 

But for many people, antipsychotic medication alone is not enough to get them back to a full and active life.

Other ways of supporting recovery will usually be added to continuing antipsychotic treatment rather than replacing it. These include a range of talking treatments ^1,2,3, usually provided by a psychologist or psychiatric nurse, and the assistance of a social worker to help with care needs, including money and housing issues.

Occupational therapists and psychiatric nurses can also help to provide a day of worthwhile, structured activity and put people in touch with services in the community that they might find useful.

• Hearing Voices Network - A charity that supports people who hear voices, see visions or have other
• Mind - Mind provides information and advice, training programmes, Mind in your area, grants and more.
• Rethink Mental Illness - National voluntary organisation that helps people with any severe mental illness, their families and carers.
• Sane - A national mental health helpline offering emotional support and practical information for people with mental illness, families, carers and professionals.

1. The National Institute for Health and Care Excellence (NICE) The National Institute for Health and Care Excellence (NICE) CG 178: Psychosis and schizophrenia in adults: prevention and management. NICE guideline. Information for the public
2. The National Institute for Health and Care Excellence (NICE). CG185. Bipolar disorder: assessment and management. NICE guideline. Information for the public
3. The National Institute for Health and Care Excellence (NICE). CG90: Depression in adults: recognition and management. NICE guideline. Information for the public
4. Fusar-Poli P, Papanastasiou E, Stahl D, et al. Treatments of negative symptoms in schizophrenia: meta-analysis of 168 randomized placebo-controlled trials. Schizophrenia Bulletin 2015;41: 892-899.
5. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013;382:951-962.
6. Taylor DM, Barnes TRE, Young AH. The Maudsley Prescribing Guidelines. Wiley-Blackwell, London. 2018.
7. Tiihonen J, Mittendorfer-Rutz E, Majak M, Mehtälä J, Hoti F, Jedenius E, et al. Real-world effectiveness of antipsychotic treatments in a nationwide cohort of 29 823 patients with schizophrenia. JAMA Psychiatry. 2017;74:686-693.
8. Yoshimura B, Yada Y, So R, Takaki M, Yamada N. The critical treatment window of clozapine in treatment-resistant schizophrenia: Secondary analysis of an observational study. Psychiatry Research 2017;250:65-70.
9. Clozapine patient information leaflet.
10. Barnes TR; Schizophrenia Consensus Group of British Association for Psychopharmacology. Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology 2011;25:567-620.
11. Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, Davis JM. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012;379:2063-71.
12. Correll CU, Rubio JM, Kane JM. What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry 2018;17:149-160.
    

This information was produced by the Royal College of Psychiatrists' Public Education Editorial Board  and reflects the best available evidence at the time of writing.

• Expert review: Professor Thomas Barnes, Carol Paton
• Series editor: Dr Philip Timms
• Series manager: Thomas Kennedy