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How Antipsychotics (probably) work

January 4 2008 at 10:02 AM
Anonymous 


Response to Study shows placebos as good as antipsychotics for the intellectually disabled.

 


1. THE BRAIN

In order to try to understand a little about how these antipsychotics work, it is best to first learn a few facts about the brain. Each human being has:

One head

One brain

Each brain has somewhere around 10,000,000,000 brain cells.

Each brain cell has lots of connections with other brain cells by means of nerve fibres (the wiring connecting brain cells together). There are about 4 million miles of nerve fibres in each brain. Some fibres may have up to 10,000 branches in them.

Each brain cell has lots of connections with other cells, possibly over 25,000! The junctions at the end of the neurones are called synapses.

As you can see, overall the brain is an extraordinarily complex part of the body.

For a better quality set of drawings and pictures, click here, although they will take a little longer to load.


2. A SYNAPSE

(the junction between brain cells)

Synapses are very important because;-

  1. They are the route by which brain cells talk to each other
  2. Synapses are of the same basic design in the brain, the heart, the legs etc.
  3. There are a lot of them
  4. If we can get chemicals (e.g. drugs) into the gap between them in the brain, we can affect the way in which brain cells talk to each other e.g. we can slow the messages down, speed the up etc.

A synapse looks like this;-

In the drawing you will see the following;-

  • Axon - A neurone (or cell body) has many axons (or nerve fibres).
  • Vesicles - these contain the transmitter.
  • Transmitters - these are small chemicals used by brain cells as messengers. They are stored in the vesicles in the nerve ending ready to be released
  • Receptors - these are structures on the surface of the receiving cell which have a space designed just for the transmitter (if the transmitter is a key, receptors are the lock into which they fit)
  • Enzymes - these surround the synapse and break down any spare transmitter that might leak out to other synapses nearby.
  • Electrical signal - This is the way in which one brain cell sends a message to another. The signal travels down the nerve fibre rather like an electrical "Mexican Wave".

3. WHAT HAPPENS WHEN A MESSAGE IS PASSED FROM ONE CELL TO ANOTHER

Depending on your browser, the pictures and words may not match perfectly, but they are both in numerical order so you should be able to work it out.

1. A brain cell decides to send a message to another cell in order to make something happen e.g. tighten a muscle, release a hormone, think about something, pass on a message etc.


2. An electrical impulse is sent from the brain cell down one of the nerve fibres/neurones towards the end. It travels at about 120 miles per hour.


3. This message or impulse arrives at the end of the nerve fibre. When it arrives, a chemical ("transmitter") is released from the nerve end.

4. The transmitter is then released and travels across the gap between the first nerve fibre and the next/receiving one.


5. The transmitter hits a receptor on the other side. It fits into it just like a key fitting into a lock.


6. When the transmitter hits the receptor, the receptor changes shape. This causes changes inside the nerve ending which sets off an electrical message in that nerve fibre on to the next brain/nerve cell. This sequence then carries on until the effect occurs e.g. the muscle moves etc.


7. The transmitter is either broken down by enzymes (10%) and removed or taken back up again into the nerve ending (i.e. recycled) - a process known as re-uptake.


8. The nerve fibre and synapse is then ready for next message


Important points;-

  • The passage of messages only works one way or one direction
  • There is only one type of transmitter per synapse
  • The transmitter allows an electrical message to be turned into a chemical message and back into an electrical message.

4. "TRANSMITTERS"

Although there are over 80 known different "transmitters" in the brain, each nerve ending only has one type. These "neurotransmitters" tend to be grouped together and each seems to have specific roles e.g.;-

Transmitter

What it seems to do

Problems if it gets out of balance

Serotonin or 5-HT

In the body, 5-HT is involved with blood pressure and gut control.

In the brain, it controls mood, emotions, sleep/wake, feeding, temperature regulation, etc.

Too much serotonin and you feel sick, less hungry, get headaches or migraines

Too little and you feel depressed, drowsy etc.

Dopamine


- there are three main groups (or pathways) of dopamine neurones in the brain

In the brain, one group controls muscle tension and another controls e.g. emotions, perceptions, sorting out what is real/important/imaginary etc.

Not enough dopamine in the first group and your muscles tighten up (e.g. as in Parkinson's Disease).

Too much dopamine in the second group gives you an overactive brain i.e. too much "perception e.g. you may see, hear or imagine things that are not real

Noradrenaline (NA)

(sometimes called "norepinephrine" or NE)

In the body, it controls the heart and blood pressure.

In the brain, it controls sleep, wakefulness, arousal, mood, emotion and drive

Too much noradrenaline and you may feel anxious, jittery etc.

Too little and you may feel depressed, sedated, dizzy, have low blood pressure etc.

Acetylcholine (ACh)

In the body, acetyl choline passes the messages which make muscles contract.

In the brain, it controls arousal, the ability to use memory, learning tasks etc.

Too much in your body and your muscles tighten up.

Too little can produce dry mouth, blurred vision and constipation, as well as becoming confused, drowsy, slow at learning etc.

Glutamate

Acts as an "accelerator" in the brain

Too much and you become anxious, excited and some parts of your brain may become overactive.

Too little and you may become drowsy or sedated

GABA

Acts as a "brake" in the brain

Too much and you become drowsy or sedated.

Too little and you may become anxious and excited

In many mental health problems, it is known that some of these transmitters get out of balance e.g. you have too much or too little of a particular transmitter.


5. PSYCHOSIS or SCHIZOPHRENIA

People with the symptoms of schizophrenia have problems with seeing things, hearing voices, imagining things, having terrifying thoughts etc. The main theory about why this happens is the so-called "Dopamine hypothesis".

We know that dopamine in one part of the brain is involved with "perception" i.e. seeing, hearing, emotions etc.

  • If you give a person a drug that increases the activity of dopamine in the brain, it can produce the symptoms of psychosis. For example, amphetamines ("Speed") and levodopa (used to treat Parkinson's Disease) sometimes do this
  • If you reduce the activity of dopamine, it reduces the symptoms of psychosis
  • People with schizophrenia have been shown to have more dopamine activity in their brains

Thus, if a person has too much dopamine activity in one part of the brain, this will produce too much "perception". For example, seeing and hearing things that aren't there (and thus thinking they come from somewhere e.g. television, radio etc), imagining too much, misinterpreting thoughts etc.

"Normal" communication

"Excess" communication e.g. as in psychosis

There are lots of other theories, e.g. genetics and how the brain develops. There may in fact be many causes and in each person there may be a combination of these. Apart from dopamine, other transmitters are probably also involved. It might be that too much glutamate is the cause of the dopamine system becoming overactive.


6. HOW THE DRUGS PROBABLY WORK

Too much dopamine activity seems to produce the symptoms of schizophrenia and psychosis. Correcting the effect of having too much dopamine should thus help to reduce the symptoms. One way of doing this is the block the dopamine receptors i.e. jam some of them up so they don't work and can't pass too many messages. This is just what antipsychotics do. They block dopamine receptors, to a greater or lesser extent.

"Normal" communication

"Excess" communication e.g. as in psychosis

"Excess" communication but with receptors blocked, and reduced messages passes

The important thing to remember is that antipsychotics probably mainly work by reducing the effect of having too much dopamine. They are NOT JUST TRANQUILLISERS, although they may help you to feel calmer. They have a much more specific way of working than just sedating you.


7. WHY YOU GET SIDE EFFECTS

As we have seen, antipsychotics block dopamine receptors. They do this by fitting into the receptor space 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 will not open the door.

Unfortunately, many antipsychotic drugs also block other receptors e.g. acetylcholine, noradrenaline, other dopamine receptors etc. They are a bit like "blunderbuss" treatments i.e. they hit the part that seems to be wrong, but also hit lots of other parts which aren't wrong. The side effects you get from drugs are from these extra "hits":

  • If a drug blocks all dopamine receptors (e.g. including the group that controls muscles and the group that controls some hormones), it upsets your muscle control, a bit like Parkinson's disease e.g. muscle stiffness, mild shaking etc. Sometimes more of a hormone called prolactin is released which confuses the body e.g. women may miss periods, produce milk etc.
  • If you block acetylcholine receptors, it reduces your learning, produces mild sedation and confusion etc.
  • If you block noradrenaline it sometimes upsets your blood pressure e.g. you feel dizzy when you stand up etc.
  • If you block some serotonin receptors, it may have an effect on your appetite and hence weight gain can occur.

It may also of course be that some of these other "hits" or blocking may actually help produce a better effect.


8. DO THE DRUGS WORK, AND FOR HOW LONG?

The big question for people with the diagnosis of schizophrenia is do the drugs really work and, if so, how long do you need to keep taking them for?

Studies in over 5600 people who had been in hospital and had their symptoms controlled by drugs and then been discharged have now shown that:

  • In the first six months, four times as many people become ill again on no antipsychotics compared to people taking antipsychotics
  • If antipsychotics are stopped, after two years there is about a one in three chance of remaining well. Not everyone becomes ill again but we don't yet know who the lucky one in three would be
  • To put this another way, if you do not take antipsychotics regularly, after two years there is a two in three chance of becoming ill again and needed to go back into hospital
  • Only one in five people who take no antipsychotics is still well after three years
  • If you stop your antipsychotic after you have got better, you are five times as likely to have to go back into hospital again within three years
  • If you stop antipsychotics and become ill again within a couple of years, you are likely to end up taking more drugs than if you had kept going

We do not know for certain what happens after three years. Many people may be advised to carry on with an antipsychotic for longer but that is decision for you and your doctor to make.


9. A SUMMARY OF OTHER FACTS YOU MAY NEED TO KNOW

Antipsychotics can be very effective in treating the symptoms of psychosis or schizophrenia e.g. hearing voices etc. The drugs are also very good at stopping the symptoms coming back, but only if you keep taking them.

Some key facts about antipsychotics:

  • The symptoms of schizophrenia or 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, imagining etc.
  • Antipsychotics help reduce the effect of having too much dopamine
  • Antipsychotics are not just tranquillisers
  • 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 return again after three to six months
  • If you do become ill again even when taking antipsychotics, you will not be as ill as if you had not taken them at all
 


 
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Responses

  1. 6. HOW THE DRUGS PROBABLY WORK - Anonymous on Jan 4, 2008, 10:03 AM
    1. remember this is an NHS document - Anonymous on Jan 4, 2008, 10:04 AM
      1. but they seem more confident about side effects - Anonymous on Jan 4, 2008, 10:14 AM
        1. "If a drug blocks all dopamine it upsets your muscle control" LIKE THIS? - paula on Jan 4, 2008, 11:47 AM
     


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