Biological therapies

• 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 the other psychotic disorders, have been used since the 1950s. They work as dopamine antagonists and include chlorpromazine.
• Atypical antipsychotics

  Drugs for schizophrenia (a psychotic disorder) developed after typical antipsychotics. They typically target a range of neurotransmitters such as dopamine and serotonin. Examples include clozapine and risperidone.
• Drug therapy for schizophrenia

  1. Antipsychotic drugs are the most common treatment

  2. Antipsychotics may be required in the short term or the long term

  3. Some people can take a short course and then stop without symptoms returning

  4. Other people may have to use them for life otherwise they may experience a recurrence
• Typical antipsychotics

  • Chlorpromazine can be taken orally or by injection
  • If taken orally it is administered daily up to a max of 1000mg, although initially doses are much smaller and for most the dosage is gradually increased to a max of 400-800mg
  • Typical prescribed doses have declined in the last 50 years
• Dopamine antagonists

  • Typical antipsychotics have been around since the 1950s (e.g., chlorpromazine)
  • They work by acting as antagonists in the dopamine system and aim to reduce the action of dopamine
  • They are strongly associated with the dopamine hypothesis
• How dopamine antagonists work

  1. Block dopamine receptors in the synapses

  2. Initially dopamine levels build up after taking chlorpromazine, but then production is reduced

  3. This normalises neurotransmission in key areas of the brain, which in turn reduces symptoms e.g. hallucinations
• Chlorpromazine - also has a sedation effect

  • It has an effect on histamine receptors which appears to lead to a sedation effect
  • It is used to calm anxious patients when they are first admitted to hospital
• Atypical antipsychotics

  • Aim to maintain or improve upon the effectiveness of drugs in suppressing the range of symptoms of psychosis and also minimise the side effects
  • There are a range of atypical antipsychotics and they do not all work in the same way - some, it is still unknown how they work
• Atypical antipsychotics

  Target dopamine AND serotonin
• Clozapine

  • Acts on dopamine, glutamate and serotonin to improve mood
  • More effective than typical antipsychotics - reduces depression and anxiety in patients as well as improving cognitive functioning
  • Improves mood, which is important as up to 50% of people suffering from SZ attempt suicide
• Risperidone

  • Developed because clozapine was involved in the deaths of some patients from a blood condition called agranulocytosis
  • Binds to dopamine and serotonin receptors, but binds more strongly to dopamine receptors and is therefore effective in a smaller dosage than most antipsychotics and has fewer side effects
• Strengths of antipsychotic drug therapy

  • Evidence shows antipsychotics are moderately effective
  • Chlorpromazine was associated with better functioning and reduced symptom severity compared with placebo
  • Clozapine is more effective than typical antipsychotics and 30-50% more effective in treatment resistant cases
• Limitations of antipsychotic drug therapy

  • Side effects (mild, serious, and fatal)
  • Theoretical objection to the use of antipsychotic drugs (dopamine hypothesis may be incorrect)
  • Doubts about the true effectiveness of antipsychotics (data exaggerating positive effects, only short-term effects reviewed)
  • Antipsychotics may simply be a 'chemical cosh' used to calm patients rather than benefit them
• One strength is the evidence shows antipsychotics are moderately effective.

  Thornley et al 2003, reviewed data from 13 trials (1121 participants) and found that chlorpromazine was associated with better functioning and reduced symptom severity compared with placebo. There is also support for the benefits of atypical antipsychotics. Meltzer et al 2012 concluded that clozapine is more effective than typical antipsychotics and that it is 30-50% more effective in treatment resistant cases. Therefore, the evidence suggests that antipsychotics are reasonably effective.
• One -ve of antipsychotic drugs is side effects (mild, serious, and fatal. Typical antipsychotics are associated with dizziness, agitation, sleepiness, weight gain, etc. Long-term use can lead to lip-smacking and grimacing due to dopamine super sensitivity. The most serious side effect is neuroleptic and malignant syndrome (NMS) caused by blocking dopamine action in the hypothalamus (can be fatal due to disrupted regulation of several body systems). Atypical antipsychotics were developed to reduce side effects but some still exist and this is a serious limitation of antipsychotic drug therapies
• Another limitation is the theoretical objection to the use of antipsychotic drugs

  The use of drugs is strongly tied up with the dopamine hypothesis and the idea that there are higher than usual levels of dopamine in the subcortex of the brain. But there is evidence that this may not be correct and that dopamine levels in other parts of the brain are too low rather than too high. If so, antipsychotics shouldn’t work. This has undermined the faith of some people that any positive effects are actually due to the pharmological effects of antipsychotics
• A further limitation is doubts about the true effectiveness of antipsychotics

  Healy 2012 suggests that data from some successful trials have been published multiple times, exaggerating the positive effects. Also, most studies only review the short term effects. Healy also suggests that as antipsychotics have powerful calming effects, it is easy to demonstrate that they have a positive effect on patients despite the fact they may not be effective in reducing psychosis. This suggests that the effectiveness of antipsychotics may be overestimated by much of the empirical research.
• A final limitation is that antipsychotic drugs may simply be a ‘chemical cosh’

  Antipsychotics may have been used in hospital situations to calm patients and make them easier for staff to work with rather than to benefit the patients themselves. Short-term use of antipsychotics to calm patients is recommended by the National Institute for Health and Care Excellence (NICE). However this practice is seen by some as a human rights abuse. This raises ethical issues in the use of antipsychotic drugs with schizophrenia patients