Biological therapy for schizophrenia.
Spec says, ‘ Drug therapy: typical and atypical antipsychotics’.
Key Terms:
- Antipsychotics = drugs used to reduce the intensity of symptoms, in
particular the positive symptoms, of psychotic disorders like
schizophrenia.
- Typical antipsychotics = the first generation of drugs for
schizophrenia and other psychotic disorders, having been used
since the 1950’s. They work as dopamine antagonists and include
chlorpromazine.
- Atypical antipsychotics = drugs for schizophrenia developed after
typical antipsychotics. They typically target a range of NT’s such as
dopamine and serotonin, examples include clozapine and
risperidone.
Drug therapy.
- The most common treatment for schizophrenia involves the use of
antipsychotic drugs. The term ‘antipsychotic’ refers to psychosis.
o A person with psychosis experiences some loos of contact with
reality, for example through hallucinations or delusions.
o Psychosis is a defining characteristic of schizophrenia.
- Antipsychotics may be required in the short or long term. Some
people can take a short course of antipsychotics then stop their use
without the return of symptoms, but other people may require to
take the antipsychotics for the rest of their lives to prevent the
reoccurrence of schizophrenia.
o Antipsychotics can be divided into typical (1st generation) and
atypical (2nd generation).
Typical antipsychotics.
- Typical antipsychotics have been around since the 1950s and
include chlorpromazine which can be taken as tablets, syrup or
injection.
o If taken orally it is administered daily up to a maximum of
1000mg although initially doses are smaller and for most
people the dosage is gradually increased to a maximum of
400 to 800mg.
Typical prescribed doses have declined over the last 50
years.
Dopamine antagonists.
- There is a strong association between the use of typical
antipsychotics like chlorpromazine and the dopamine hypotheses.
- Typical antipsychotics work by acting as antagonist is in the
dopamine system.
o Antagonists are chemicals which reduce the action of the NT.
o Dopamine antagonists work by blocking dopamine receptors
in the synapses of the brain, reducing the action of dopamine.
, - Initially when an individual begins taking chlorpromazine dopamine
levels build up, but then its production is reduced.
o According to the dopamine hypothesis of schizophrenia this
dopamine antagonist effects normalises neurotransmission in
key areas of the brain, reducing symptoms like hallucinations.
Sedation effect.
- As well as having antipsychotic properties chlorpromazine is also an
effective sedative.
- This is believed to be related to its effect on histamine receptors but
it is not fully understood how this leads to sedation.
- Chlorpromazine is often used to calm individuals not only with
schizophrenia but also with other conditions.
o This has often been done when patients are first admitted to
hospital and are very anxious.
o Syrup is absorbed faster than tablets and so it tends to be
given when chlorpromazine and is used for its sedative
properties.
Atypical antipsychotics.
- These have been used since the 1970’s. The aim in developing
newer antipsychotics was to maintain or improve upon the
effectiveness of drugs in suppressing the symptoms of psychosis
and also minimise the side effects of the drugs used.
o There are a range of atypical antipsychotics and they do not
all work in the same way. In fact we do not know how some of
them work.
Clozapine.
- Clozapine was developed in the 1960’s, and first trialled in the
1970’s.
- It was withdrawn for a while in the 1970s following the deaths of
some patients from a blood condition called agranulocytosis.
o However, in the 1980’s, when it was discovered to be more
effective than typical antipsychotics, clozapine was
remarketed as a treatment for schizophrenia to be used when
other treatment failed.
Those who take it have to have regular blood tests to
ensure they they do not develop agranulocytosis.
o Because of its potentially fatal side effects clozapine is not
available as an injection and daily dosage is a little lower,
typically 300 to 450mg a day.
- Clozapine binds to dopamine receptors in the same way that
chlorpromazine does, but in addition it acts on serotonin and
glutamate receptors.
o It is believed that this action helps to improve mood, reduce
anxiety and depression and improve cognitive functioning.
- The mood enhancing effects of clozapine mean that it is sometimes
prescribed when an individual is considered at high risk of suicide.
, o This is important as 30 to 50% of people with schizophrenia
attempt suicide at some point.
Risperidone.
- Risperidone is a more recently developed atypical antipsychotic,
having been around since the 1990’s.
- It was developed in an attempt to procure a drug as effective as
clozapine but without its serious side effects, it can be taken in
tablets, syrup or injection and initially a small dose is given and built
up from here.
- Risperidone is believed to bind to dopamine and serotonin receptors
but binds more strongly to these dopamine receptors and so is more
effective in smaller doses than other antipsychotics, with fewer side
effects.
Evaluation.
Evidence for effectiveness.
- One strength of antipsychotics is that there is evidence to support
their effectiveness.
- There is a large body of evidence to support the idea that both
typical and atypical antipsychotics are at least moderately effective
in tackling symptoms of schizophrenia.
o Thornley et al reviewed studies comparing the effects of
chlorpromazine to control conditions.
Data from 13 trials with a total of 1121 P’s showed that
chlorpromazine was associated with better overall
functioning and reduced symptoms severity as
compared to placebo.
o There is also evidence for the benefits of atypical
antipsychotics.
o In a review Meltzer concluded that clozapine is more effective
than typical antipsychotics and other atypical antipsychotics,
and this it is effective in 30 to 50% of treatment resistant
cases where typical antipsychotics have failed.
- This means that, as far as we can tell, antipsychotics do work.
HOWEVER.
- Healy has suggested serious flaws with evidence for effectiveness.
- For example, most studies are of short term effects only and some
successful trials have had their data published multiple times,
exaggerating the size of the evidence base for its positive effects.
- Also, because antipsychotics have powerful calling effects, it is easy
to demonstrate that they have some positive effect on people
experiencing the symptoms of schizophrenia. This is not the same
as saying they actually reduce the severity of psychosis.
- This means that the evidence base for the antipsychotic
effectiveness is less impressive than it first appears.
Serious side effects.
- One limitation of antipsychotic drugs is the likelihood of side effects.
Spec says, ‘ Drug therapy: typical and atypical antipsychotics’.
Key Terms:
- Antipsychotics = drugs used to reduce the intensity of symptoms, in
particular the positive symptoms, of psychotic disorders like
schizophrenia.
- Typical antipsychotics = the first generation of drugs for
schizophrenia and other psychotic disorders, having been used
since the 1950’s. They work as dopamine antagonists and include
chlorpromazine.
- Atypical antipsychotics = drugs for schizophrenia developed after
typical antipsychotics. They typically target a range of NT’s such as
dopamine and serotonin, examples include clozapine and
risperidone.
Drug therapy.
- The most common treatment for schizophrenia involves the use of
antipsychotic drugs. The term ‘antipsychotic’ refers to psychosis.
o A person with psychosis experiences some loos of contact with
reality, for example through hallucinations or delusions.
o Psychosis is a defining characteristic of schizophrenia.
- Antipsychotics may be required in the short or long term. Some
people can take a short course of antipsychotics then stop their use
without the return of symptoms, but other people may require to
take the antipsychotics for the rest of their lives to prevent the
reoccurrence of schizophrenia.
o Antipsychotics can be divided into typical (1st generation) and
atypical (2nd generation).
Typical antipsychotics.
- Typical antipsychotics have been around since the 1950s and
include chlorpromazine which can be taken as tablets, syrup or
injection.
o If taken orally it is administered daily up to a maximum of
1000mg although initially doses are smaller and for most
people the dosage is gradually increased to a maximum of
400 to 800mg.
Typical prescribed doses have declined over the last 50
years.
Dopamine antagonists.
- There is a strong association between the use of typical
antipsychotics like chlorpromazine and the dopamine hypotheses.
- Typical antipsychotics work by acting as antagonist is in the
dopamine system.
o Antagonists are chemicals which reduce the action of the NT.
o Dopamine antagonists work by blocking dopamine receptors
in the synapses of the brain, reducing the action of dopamine.
, - Initially when an individual begins taking chlorpromazine dopamine
levels build up, but then its production is reduced.
o According to the dopamine hypothesis of schizophrenia this
dopamine antagonist effects normalises neurotransmission in
key areas of the brain, reducing symptoms like hallucinations.
Sedation effect.
- As well as having antipsychotic properties chlorpromazine is also an
effective sedative.
- This is believed to be related to its effect on histamine receptors but
it is not fully understood how this leads to sedation.
- Chlorpromazine is often used to calm individuals not only with
schizophrenia but also with other conditions.
o This has often been done when patients are first admitted to
hospital and are very anxious.
o Syrup is absorbed faster than tablets and so it tends to be
given when chlorpromazine and is used for its sedative
properties.
Atypical antipsychotics.
- These have been used since the 1970’s. The aim in developing
newer antipsychotics was to maintain or improve upon the
effectiveness of drugs in suppressing the symptoms of psychosis
and also minimise the side effects of the drugs used.
o There are a range of atypical antipsychotics and they do not
all work in the same way. In fact we do not know how some of
them work.
Clozapine.
- Clozapine was developed in the 1960’s, and first trialled in the
1970’s.
- It was withdrawn for a while in the 1970s following the deaths of
some patients from a blood condition called agranulocytosis.
o However, in the 1980’s, when it was discovered to be more
effective than typical antipsychotics, clozapine was
remarketed as a treatment for schizophrenia to be used when
other treatment failed.
Those who take it have to have regular blood tests to
ensure they they do not develop agranulocytosis.
o Because of its potentially fatal side effects clozapine is not
available as an injection and daily dosage is a little lower,
typically 300 to 450mg a day.
- Clozapine binds to dopamine receptors in the same way that
chlorpromazine does, but in addition it acts on serotonin and
glutamate receptors.
o It is believed that this action helps to improve mood, reduce
anxiety and depression and improve cognitive functioning.
- The mood enhancing effects of clozapine mean that it is sometimes
prescribed when an individual is considered at high risk of suicide.
, o This is important as 30 to 50% of people with schizophrenia
attempt suicide at some point.
Risperidone.
- Risperidone is a more recently developed atypical antipsychotic,
having been around since the 1990’s.
- It was developed in an attempt to procure a drug as effective as
clozapine but without its serious side effects, it can be taken in
tablets, syrup or injection and initially a small dose is given and built
up from here.
- Risperidone is believed to bind to dopamine and serotonin receptors
but binds more strongly to these dopamine receptors and so is more
effective in smaller doses than other antipsychotics, with fewer side
effects.
Evaluation.
Evidence for effectiveness.
- One strength of antipsychotics is that there is evidence to support
their effectiveness.
- There is a large body of evidence to support the idea that both
typical and atypical antipsychotics are at least moderately effective
in tackling symptoms of schizophrenia.
o Thornley et al reviewed studies comparing the effects of
chlorpromazine to control conditions.
Data from 13 trials with a total of 1121 P’s showed that
chlorpromazine was associated with better overall
functioning and reduced symptoms severity as
compared to placebo.
o There is also evidence for the benefits of atypical
antipsychotics.
o In a review Meltzer concluded that clozapine is more effective
than typical antipsychotics and other atypical antipsychotics,
and this it is effective in 30 to 50% of treatment resistant
cases where typical antipsychotics have failed.
- This means that, as far as we can tell, antipsychotics do work.
HOWEVER.
- Healy has suggested serious flaws with evidence for effectiveness.
- For example, most studies are of short term effects only and some
successful trials have had their data published multiple times,
exaggerating the size of the evidence base for its positive effects.
- Also, because antipsychotics have powerful calling effects, it is easy
to demonstrate that they have some positive effect on people
experiencing the symptoms of schizophrenia. This is not the same
as saying they actually reduce the severity of psychosis.
- This means that the evidence base for the antipsychotic
effectiveness is less impressive than it first appears.
Serious side effects.
- One limitation of antipsychotic drugs is the likelihood of side effects.
