Biological therapy for Schizophrenia Flashcards
what are antipsychotics?
The most common treatment for schizophrenia - ‘antipsychotic’ refers to psychosis
someone with psychosis experiences some loss of contact with reality - hallucination’s or delusions
psychosis is a defining characteristic of schizophrenia and related disorders
antipsychotics maybe required in short or long term (some people can have short course then stop without return of symptoms - unlike others who would have to use them for life as symptoms could return
antipsychotics can be divided into typical and newer atypical or second generation drugs.
what is the history/ dosage of typical antipsychotics?
they have been around since 1950s - including chlorpromazine - can be taken as tablets, syrup or injection
oral administration - maximum of 1000mg - though initial dose is much smaller for most people and is gradually increased to maximum of 400 to 800mg
typical prescribed doses have declined over the last 50 years (Lui and de Hann)
what are dopamine antagonists?
strong association between typical antipsychotics and dopamine hypothesis
typical antipsychotics like chlorpromazine work by acting as antagonists in the dopamine system.
antagonists are chemicals which reduce the action of a neurotransmitter - dopamine antagonists work by blocking dopamine receptors in the synapses of the brain, reducing the action of dopamine
what happens when someone begins taking chlorpromazine ( a typical antipsychotic)
dopamine levels build up, but then its production is reduced - according to the dopamine hypothesis of schizophrenia this dopamine-antagonist effect normalises neurotransmission in key areas of the brain - reducing symptoms like hallucinations
what is the sedation effect of typical antagonists?
chlorpromazine is an effective sedative - believed to be related to it’s 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 - this has often been done when patients are first admitted to hospitals and when they are very anxious
syrup is absorbed faster than tablets so it tends to be given when chlorpromazine is used for its sedative properties.
what is the history of atypical antipsychotics?
they have been used since the 1970s - aim in developing newer antipsychotics was to maintain/ improve upon the effectiveness of drugs in suppressing the symptoms of psychosis and also minimise the side effects of the drugs used
there are a range of atypical antipsychotics and they do not all work in the same way - it is not known how all of them work
explain the history of clozapine / dose- an atypical antipsychotic?
it was developed in 1960s - first trialled in early 1970s - but some patients died from blood condition called agranulocytosis
but in the 1980s, when it was discovered to be more effective than typical antipsychotics, clozapine was remarketed as a treatment for schizophrenia - used when other treatments failed
still used today in this way - people taking it have regular blood tests to ensure they are not developing agranulocytosis
due to potential fatality, clozapine is not available as an injection - daily dosage is little lower than for chlorpromazine - typically 300 - 450 mg a day
how does clozapine work (glutamate and serotonin)?
it binds to dopamine receptors in the same way that chlorpromazine does - but it also acts on serotonin and glutamate receptors
it is believed that this helps improve mood and reduce depression and anxiety in patients - so may improve cognitive functioning
mood enhancing effects of clozapine mean it is sometimes prescribed when an individual is considered at high risk of suicide
this is importnant as 30-50% of people with schizophrenia attempt suicide at some point
What is Risperidone? (atypical antipsychotic)
it is a more recently developed atypical antipsychotic - it has been around since the 1990s.
it was developed to have the same effects of clozapine without serious side effects
risperidone can be taken as tablets, syrup or injection and lasts around 2 weeks
similar to other antipsychotics, initial dose is small and built up to a typical daily dose of 4-8mg and maximum of 12mg
risperidone is believed to bind with dopamine and serotonin receptors - it binds more strongly to dopamine receptors than clozapine and so more effective in much smaller doses than most antipsychotics.
there’s some evidence suggesting that this leads to fewer side effects than other antipsychotics
Strength - evidence for antipsychotic effectiveness
large body of evidence supporting that typical and atypical antipsychotics are at least moderately effective tackling symptoms of schizophrenia
Thornley reviewed studies comparing the effects of chlorpromazine to control conditions and data from 13 trials with total of 1112 participants showed that chlorpromazine was associated with better overall functioning and reduced symptom severity - as compared to placebo
also evidence from Meltzer to support benefits of atypical antipsychotics. he concluded that clozapine is more effective than typical antipsychotics and other atypical antipsychotics - reviewed as effective in 30-50% of treatments-resistant cases where typical antipsychotics have failed.
means that antipsychotics work
counterpoint to evidence for effectiveness
Healy suggested serious flaws with evidence for effectiveness. e.g. most studies are short term only and some successful trials have had data published multiple times - exaggerating the size of evidence base for positive effects
also antipsychotics have powerful calming effects, it is easy to show that they have some positive effect on people experiencing symptoms of schizophrenia - not the same as saying they really reduce the severity of psychosis
means evidence base for antipsychotic effectiveness is less impressive that it appears
limitation - side effects
limitation of antispychotics is the likelihood of side effects
typical antipsychotics - associated with dizziness, agitation, sleepiness, stiff jaw, weight gain and itchy skin
long term use can result in tardive dyskinesia caused by dopamine super sensitivity and causes involuntary facial movements such as grimacing, blinking and lip smacking
most serious effect of antipsychotics is neuroleptic malignant syndrome - believed the be caused when the drug blocks dopamine actions in the hypothalamus - area associated with the regulation of a number of body systems
NMS results in high temperature, delirium and coma and can be fatal - estimates of this range from 0.1% to just over 2%
means antipsychotics can do harm as well as good and individuals who experience these may avoid such treatments
limitation - don’t know why they work
our understanding of the mechanism of how antipsychotic drugs work is strongly tied up with the original dopamine hypothesis - that symptoms of schizophrenia are linked to high levels of dopamine activity in the subcortex of the brain
but this is the original hypothesis which is not a complete explanation of schizophrenia - in fact dopamine levels in other parts of the brain are too low rather than too high - if this is true, then antipsychotics should not work.
there are also questions over effectiveness of antipsychotics so this adds to the argument that they are ineffective
means that at least some of the antipsychotics may not be the best treatment to opt for - perhaps some other factor is involved in their apparent success
extra - use of antipsychotics
antipsychotics have been used in hospital to calm people with schizophrenia and make them easier for staff to work with (this is believed) rather than for the benefits of the people themselves (Moncrieff)
but calming people distressed by hallucinations and delusions almost certainly makes them feel better and allows them to engage with other treatments - CBT, and services such as meeting with a social worker
