biological therapy for schizophrenia Flashcards
why are antipsychotic drugs used to treat schizophrenia?
- ‘antipsychotic’ refers to psychosis
- a person with psychosis experiences some loss of contact with reality eg. through hallucinations or delusions
- psychosis is a defining characteristic of schizophrenia and related disorders
how can the use of antipsychotics vary between different people?
- used short or long term
- some people can take a short course then stop their use without the return of symptoms
- others may require them for life or face the likelihood of recurrence
what are the 2 types of antipsychotics?
- typical (traditional)
- atypical (newer, 2nd gen)
when have a/typical antipsychotics been used since?
- typical - 1950s
- atypical - 1970s
describe how typical antipsychotics are given
- taken as tablets, syrup or by injection
- if taken orally it is administered daily up to a max of 1000 mg
- initally doses are much smaller
- for most people, dosage is gradually increased to a maximum of 400-800 mg
typical antipsychotics: liu and de haan (2009)
typical prescribed doses have declined over the last 50 years
what are antagonists?
chemicals which reduce the action of a neurotransmitter
how do typical antipsychotics (eg. chlorpromazine) work as dopamine antagonists?
- dopamine receptors in synapses are blocked
- action of dopamine is reduced
- initially, dopamine level build up, but then its production is reduced
what is the consequence of the dopamine-antagonist effect?
normalises neurotransmission in key areas of the brain, reducing symptoms like hallucinations
typical antipsychotics: sedation effect
- may be due to its effect on histamine receptors but not fully understood how this leads to sedation
- chlorpromazine can be used to calm individuals with schizophrenia and other conditions
- often used when patients are first admitted to hospitals and are very anxious
why was a newer antipsychotic developed?
- to maintain or improve upon effectiveness of drugs in suppressing symptoms of psychosis
- to minimise side effects
describe the history of clozapine
- developed in 1960s
- first trialled in early 1970s
- withdrawn for a while in 1970s after some patients died from a blood condition (agranulocytosis)
- in 1980s, it was discovered to be more effective than typical antipsychotics
- remarketed as a treatment for schizophrenia to be used when other treatments failed
how is clozapine used nowadays?
- people taking it have regular blood tests to ensure they are not developing agranulocytosis
- due to its potentially fatal side effects, it is unavailable as an injection
- daily dosage is a little lower than for chlorpromazine, typically 300-450 mg a day
how does clozapine work?
- binds to dopamine receptors in the same way chlorpromazine does
- also acts on serotonin and glutamate receptors
- this action helps improve mood and reduce depression and anxiety in patients, improving cognitive functioning
why are the mood-enhancing effects of clozapine important?
- sometimes prescribed when an individual is considered at high risk of suicide
- 30-50% of people with schizophrenia attempt suicide at some point
describe the development of risperidone
- been around since 1990s
- developed in an attempt to produce a drug as effective as clozapine without its serious side effects
how is risperidone given?
- taken in the form of tablets, syrup or an injection that lasts for ~2 weeks
- small doses are initally given
- built up to a typical daily does of 4-8 mg
- maximum of 12 mg
how does risperidone work?
- like clozapine, it binds to dopamine and serotonin receptors
- binds more strongly to dopamine receptors than clozapine so is effective in much smaller doses than clozapine
- effective in much smaller doses than most antipsychotics, which may lead to fewer side effects
what is an agonist?
chemical which binds to receptor and causes same action as what normally binds to the receptor
evaluation: evidence for effectiveness (thornley et al. 2003)
- reviewed data from 13 trials with a total of 1121 ps comparing the effects of chlorpromazine to control conditions
- chlorpromazine was associated with better overall functioning and reduced symptom severity compared to placebo
evaluation: evidence for effectiveness (meltzer 2012)
- concluded that clozapine is more effective than typical antipsychotics and other atypical antipsychotics
- effective in 30-50% of treatment-resistant cases where typical antipsychotics have failed
evaluation: evidence is flawed (healy 2012)
- most studies are of short-term effects only
- some successful trials have had their data published multiple times, exaggerating the size of the evidence base for positive
effects - antipsychotics have powerful calming effects so it is easy to demonstrate they have some positive effect on people experiencing the symptoms of schizophrenia
- severity of psychosis is not necessarily reduced
evaluation: serious side effects of typical antipsychotics
- dizziness, agitation, sleepiness, stiff jaw, weight gain, and itchy skin
- long-term use can result in tardive dyskinesia
- most serious side effect is NMS
- lower adherence to medical regimen makes treatment ineffective
side effects: tardive dyskinesia
- caused by dopamine supersensitivity
- causes involuntary facial movements eg. grimacing, blinking, lip-smacking
side effects: neuroleptic malignant syndrome (NMS)
- believed to be caused when drug blocks dopamine action in hypothalamus, which is assicated with the regulation of a number of body systems
- results in high temperature, delirium, coma and can be fatal
- fatality frequency range is <0.1-2%
evaluation: don’t understand mechanism
- based on dopamine hypothesis
- original dopamine hypothesis is an incomplete explanation
- dopamine levels in other parts of the brain are too low rather than too high, so antipsychotics shouldn’t work
- other factors involved in their apparent success
evaluation: chemical cosh (moncrieff 2013)
widely believed that antipsychotics have been used in hospital situations to calm people with schizophrenia and make them easier for staff to work with, rather than for the benefits to the people themselves
evaluation: other benefits of prescribing antipsychotics
- calming people distressed by hallucinations and delusions should make them feel better
- allows them to engage with other treatments eg. CBT and services, such as meeting with a social worker
