Biological therapies for schizophrenia

• The most common treatment for schizophrenia involves the use of antipsychotic drugs
• What is psychosis?


  A person with psychosis experiences some loss of contact with reality and is a defining characteristic of schizophrenia and related disorders
• Antispychotics can be required in the short or long run

  • some people can take a short course of antipsychotics then stop their use without the return of symptoms
  • Other people may require antipsychotics for life or face the likelihood of a recurrence of schizophrenia
• Antipsychotics can be divided into typical (traditional) and newer atypical (second generation) drugs
• How long have typical psychotics been around?

  Since the 1950s
• Examples of typical antipsychotics

  Chlorpromazine

  • can be taken as tablets (maximum of 1000 mg daily but normally doesn’t are much smaller and gradually increased to a maximum of 400 to 800 mg), syrup or by injection
  • typical prescribed doses have declined over the last 50 years
  • suppresses hallucinations and delusions by blocking receptors of dopamine

  Fluphenazine

  • suppresses hallucinations and delusions by blocking receptors of dopamine

  Haloperidol

  • Blocks dopamine receptors and helps suppress hyperactivity, agitation and disorganised thought
• There’s a strong association between the use of typical antipsychotics like chlorpromazine and the dopamine hypothesis
• Typical antipsychotics work by acting as antagonists in the dopamine system
• What are antagonists?


  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
• Initially when an individual begins taking chlorpromazine dopamine levels build up 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
• Chlorpromazine has a sedative effect

  • believed to be talented to its effect on histamine receptors but its not fully understood how it leads to sedation
• Chlorpromazine is often used to calm individuals not only with schizophrenia but also with other conditions as often patients are admitted to hospital and very anxious
• Snce when have atypical antipsychotics been used?


  used since the 1970s
• The aim in developing newer antipsychotics was to maintain or even improve upon the effectiveness of drugs in suppressing the symptoms of psychosis and also minimise the side effects
• There are a range of antipsychotics and they don‘t all work in the same way and some we don’t know how they work
• Clozapine


  Developed in the 1960s and 1st trialed in the early 1970s

  withdrawn for a while in the 1970s due to some patients dying from the blood condition agranulocytosis but was discovered to be more effectI’ve than typical antipsychotics in the 1980s and so was remarketed as a treatment used when others failed.

  Used today but people take regular blood tests to ensure they aren’t developing agranulocytosis

  daily dose is typically of 400 to 450 mg a day

  Binds to dopamine receptors in the same way that chlorpromazine does
• Clozapine lso acts on serotonin and glutamate receptors whic is believed to improve mood and reduce depression and anxiety in patients and may even improve cognitive functioning

  The mood enhancing side effects of clozapine mean that it’s sometimes prescribed when someone’s at high risk of suicide
• Risperidone?


  More recently developed atypical antipsychotic which has been around since the 1990s

  developed in an attempt to produce a drug as effective as clozapine but without serious side effects

  Can be taken as tablets (small dose normally given which is built up to a typical daily does of 4 to 8 mg and a maximum of 12 mg), syrup or an injection (lasts around 2 weeks)

  Believed to bind to dopamine and serotonin receptors

  • binds more strongly to dopamine receptors than clozapine and so is effective in much smaller doses than others

  evidence suggests that it leads to leads side effects
• Evidence for effectiveness of typical antipsychotics- A03

  Large body of evidence supports the effectiveness of typical antipsychotics in tackling symptoms of schizophrenia

  Thomley et al. (2003)

  • reviewed studies comparing the effects of chlorpromazine to control conditions
  • data from 13 trials with a total of 1121 participants showed that chlorpromazine was associated with better overall functioning and reduced symptoms severity compared to a placebo
• Evidence for effectiveness of atypical antipsychotics- A03

  Evidence to support the idea that atypical antipsychotics are at least moderately effective in tackling the symptoms of schizophrenia

  Meltzer (2012)

  • in a review concluded that clozapine is more effective than typical antipsychotics and other atypical antipsychotics (effective in 30 to 59% of treatment resistant cases where typical antipsychotics have failed)
• Real world application- A03

  Antipsychotics can also be used in hospital situations to calm people with schizophrenia to calm people with schizophrenia and make them easier fro staff to work with

  Calming people distressed by hallucinations and delusions makes them feel better and allows them to engage with other treatments (e.g. CBT) and services

  • but some argue that this isn’t actually helpful for people with schizophrenia and is only a short term solution
• Bad research support-A03


  Healy (2012) suggested serious flaws with evidence for effectiveness

  • e.g most studies are short term effects and some successful trials had their data published multiple times, exaggerating the size of the supportive evidence base

  Due to their calming effects it’s easy to demonstrate that antipsychotics have some positive effect on people experiencing schizophrenic symptoms

  • isn’t the same as saying they really reduce the severity of psychosis

  Tendency for only research supporting preconceived ideas

  • due to funding from drug companies
• Serious side effects- A03


  Typical antipsychotics are assoicated with a range of side effects like dizziness, agitation, sleepiness, stiff jaw, weight gain and itchy skin.

  Tardive dyskenesia

  • caused by dopamine sensitivity and causes involuntary facial movements

  neuroleptic malignant syndrome (NMS)

  • caused when drug blocks dopamine action to hypothalamus which is associated with the operation of multiple bodily functions
  • NMS results in high temperature, delirium, comas and can be fatal

  so antipsychotics can also do harm and may be avoided which would make treatment ineffective
• Mechanism unclear- A03


  We don’t know why antipsychotics work and our understanding is strongly tied up with the original dopamine hypothesis

  • idea that symptoms of schizophrenia are linked to high dopamine activity in the subcortex of the brain

  but the original dopamine hypothesis isn’t a complete explanation for schizophrenia

  • dopamine in other parts of the brain are too low not too high which would suggest that most antipsychotics shouldn’t work

  May suggest that some antipsychotics may not be the best treatment and maybe some other factor is involved in their apparent success