Section two – how we think antipsychotics work
a.
How we think the symptoms of psychosis happen
People with psychosis have problems with seeing things that aren’t there, hearing voices,
imagining things, and having terrifying thoughts. Psychosis can be a symptom of many
conditions e.g. schizophrenia, depression, anxiety and bipolar disorder.
The main theory about why this happens is the so-called ‘Dopamine Hypothesis’. Dopamine in
the brain helps you focus on things and trying to make sense of them. It then decides what is
important and what isn’t, and what to do about it. If it is overactive you can start to
concentrate more on something that might be a danger. Things become over-important and
more threatening. For example, seeing and hearing things that aren’t there (and thus thinking
they come from somewhere e.g. television, radio), imagining too much and misinterpreting
thoughts. Such as pictures of eyes that start to become over-important and follow you round.
Some of the reasons we know this are that:
 If you give a person a drug that increases the level or activity of dopamine in the brain, it
can produce the symptoms of psychosis. For example, amphetamines (‘Speed’), cannabis
and levodopa (used to treat Parkinson’s Disease) can sometimes do this
 If you reduce the level or activity of dopamine, it reduces the symptoms of psychosis
 People with psychosis have been shown to have more dopamine activity in their brain.
‘Normal’ communication
‘Excess’ communication e.g. as in psychosis
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a.
How we think the symptoms of psychosis happen (part 2)
This section is a bit complex. You may want to miss this at the moment and come back to it later. It is also an
attempt to explain something very complex in a simple way.
There is possibly a series of events that can lead to schizophrenia:
1. Someone may be born with a dopamine system in the brain that is a bit too overactive. Or may become
overactive as the brain develops or if things happen to it
2. The person may then come under stress and/or have a trigger. There are many things in the person’s
environment that cause stress (and who grows up without any stress?). These might include social isolation,
discrimination, moving to an inner city area with loss of friends or social support that can increase stress and
dopamine. There may then be a trigger e.g. an event of isolation, stress, drugs
3. That stress causes the dopamine system to become more active
4. That increases dopamine in the brain, which can then lead to psychosis
5. That psychosis increases stress and upset
6. That stress increases dopamine levels
7. And then you start again at (4) above.
How therapies may help
 Antipsychotics can help by reducing the effects of more dopamine in the brain. This might help stop
schizophrenia in the first place. It can also help reduce the symptoms when they are in full swing or when
they are not caused by schizophrenia.
 Talking Therapies can help the person cope with the stresses they may come under. This may reduce the
dopamine increase.
 Support can help reduce the stresses as well.
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b. How we think antipsychotics work
We know that too much dopamine can produce the symptoms of psychosis. Thus, correcting
the effect of having too much dopamine should help to reduce the symptoms. One way of
doing this is the block dopamine receptors i.e. jam some of them up so they don’t work and
can’t pass too many messages. This is what antipsychotics do.
Normal nerve activity
Increased activity due to extra dopamine being released. We don’t
know for sure why this happens.
More dopamine hitting dopamine receptors means more and
stronger messages. This can mean parts of the brain become
overactive, which is where the psychosis comes from.
01e05
b
4i
Antipsychotics block dopamine receptors. This is a bit like putting
the wrong Yale key into a Yale lock – it goes in, doesn’t have any
effect and stops the proper key going in.
4ja
When the next over-excited message arrives it can’t hit all the
receptors because some are blocked.
4ka
Dopamine hits fewer receptors.
5cd
The result is not such an over-excited message, the brain is calmer
and the symptoms caused by too much dopamine are reduced. It
doesn’t cure anything but can help you live with it.
The important thing to remember is that antipsychotics probably mainly work by reducing the
effect of having too much dopamine. They are NOT TRANQUILLISERS, although they may
help you to feel calmer. They have a much more specific way of working than just sedating
you.
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c. How we think that aripiprazole works
Aripiprazole seems to work in a slightly different way to other antipsychotics.
What it does the same as other antipsychotics:
 Aripiprazole blocks dopamine receptors and stops the excess dopamine over-stimulating
your brain
 This reduces the symptoms caused by this excess dopamine e.g. hallucinations, being
paranoid.
What it does differently:
 Aripiprazole blocks the receptors but at the same time partly stimulates or boosts them
 This is a bit like a key going into a lock and jamming it but also allowing the door to open a
little bit, allowing some messages to get through, but not too many
 It boosts the receptors up to about 30% (about a third) of normal.
What this means:
 Aripiprazole acts more like a regulator of dopamine
 It doesn’t have the same side effects as the other antipsychotics of just blocking dopamine
e.g. feeling sleepy, muscle stiffness and increased prolactin
 It can be quite a jolt to your brain when starting so it is always best to start slowly e.g. 5mg
or 10mg a day
 Aripiprazole seems to suit some people and not others.
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d. How and why you can get side effects from antipsychotics
As we have seen, antipsychotics block dopamine receptors. They do this by fitting into the
receptor usually reserved for dopamine. When dopamine comes along, it cannot fit into the
receptor and cannot pass the message. It is a bit like putting the wrong Yale key into a Yale
lock. You can get the key in, but it doesn’t have any effect and stops the proper key going in.
Although antipsychotics mainly block dopamine receptors, they also affect other transmitter
systems e.g. acetylcholine, serotonin and histamine.
Dopamine:
 If a medicine blocks the effect of dopamine on some dopamine receptors in the area that
controls perceptions this can help reduce the symptoms caused by too much dopamine e.g.
delusions and hallucinations
 However, some antipsychotics block dopamine receptors in other parts of the brain as well
 If it blocks dopamine in the part of the brain that controls muscle tension this upsets your
muscle control, a bit like Parkinson’s disease, and you can get muscle stiffness and mild
shaking
 If it blocks dopamine in the part of the brain that controls a hormone called prolactin, then
more prolactin is released which confuses the body e.g. periods may stop or be irregular,
breasts produce milk.
Serotonin:
 If you block some serotonin receptors, it may have an effect on your appetite (making you
feel hungrier, less full when you’ve eaten) and hence weight gain can occur.
Noradrenaline:
 If a medicine blocks the effect of noradrenaline then this can sometimes upset your blood
pressure e.g. you may feel dizzy when you stand up quickly.
Histamine:
 Histamine is produced by the brain to keep us awake
 If a medicine also blocks histamine in the brain, then this can make you feel sleepy. This is
the same as if you take one of the older antihistamines such as chlorphenamine (also called
chlorpheniramine, Piriton® or dexchlorpheniramine) or promethazine (Phenergan®) for hay
fever or allergy. The newer antihistamines such as cetirizine don’t get into the brain so don’t
make you feel sleepy
 In the body histamine increases inflammation and allergy
 Blocking histamine might also lead to some weight gain.
Acetylcholine:
 If a medicine also blocks acetylcholine, then this can make you feel a bit slow, sleepy and
confused. You may also get a dry mouth, blurred vision, finding it hard to wee and poo.
It may also of course be that some of these other transmitter effects may actually help produce
a better effect or be part of how they work. However, no one has yet made a drug that has no
effect on dopamine but still helps psychosis in humans.
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e. Some key facts about antipsychotics
 The symptoms of psychosis are probably caused by too much dopamine activity in the brain
 This produces overactivity in the part of the brain that controls seeing, hearing, and
imagining
 Symptoms of some other conditions also seem to be at least partly caused by extra
dopamine. Antipsychotics can help manage e.g. bipolar mood disorder (especially mania),
depression, personality disorders, poor sleep, aggression, some symptoms of dementia,
self-injurious behaviour, tics, Tourette’s Syndrome and ADHD
 Antipsychotics help reduce the effects of having too much dopamine
 Antipsychotics are not tranquillisers, although they may help you feel calmer
 They do not directly alter personality
 They are not addictive and are not habit forming, but if you stop taking them suddenly the
symptoms could come back
 They do not appear to lose their effect if you keep taking them
 If you stop antipsychotics, your symptoms may not return again for several months (and
indeed you may even feel better for a while) but may then come back again after three to
six months
 If you do become unwell again even when taking an antipsychotic, you will not be as unwell
as if you had not been taking one at all.
The small print: This booklet is to help you understand about how we think medicines may work for mental health problems.
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