Antipsychotics Flashcards
Dopamine antagonists
Typical antipsychotic drugs (e.g. chlorpromazine) have been around since the 1950s. 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.
Block dopamine receptors in the synapses
Dopamine antagonists work by blocking dopamine receptors in the synapses in the brain, reducing the action of dopamine. Initially, dopamine levels build up after taking chlorpromazine, but then production is reduced.
Chlorpromazine also has sedation effects
Chlorpromazine also has an effect on histamine receptors which appears to lead to a sedation effect. It is also used generally to calm anxious patients when they are first admitted to hospital.
Newer drugs
The aim of developing newer antipsychotics was to maintain or improve upon the effectiveness of drugs in suppressing the symptoms of psychosis and also to minimise the side effects of the drugs used.
Clozapine acts on dopamine, glutamate and serotonin to improve mood
Clozapine binds to dopamine receptors as chlorpromazine does but also acts on serotonin and glutamate receptors. This drug was more effective than typical antipsychotics - clozapine reduces depression and anxiety as well as improving cognitive functioning. It also improves mood, which is important as up to 50% of people with schizophrenia attempt suicide.
Risperidone is as effective as clozapine but safer
Risperidone was developed in the 1990s because clozapine was involved in the death of some people from a blood condition called agranulocytosis. Risperidone like clozapine binds to dopamine and serotonin receptors. But risperidone binds more strongly to dopamine receptors and is therefore more effective in smaller doses than most antipsychotics and has fewer side effects.
A03:One limitation of antipsychotic drugs is the likelihood of side effects.
Typical antipsychotics are associated with dizziness, agitation, sleepiness, weight gain, etc. Long term use can lead to lip smacking and grimacing due to dopamine supersensitivity (= tardive dyskinesia). The most serious side effect is neuroleptic malignant syndrome (NMS) caused by blocking dopamine action in the hypothalamus (can be fatal due to disrupted regulation of several body systems).
This means that antipsychotics can do harm as well as good and individuals may avoid them (reducing effectiveness).
A03: Another limitation of antipsychotics is that we do not know why they work.
The use of most of these 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 people with schizophrenia. 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, most antipsychotics shouldnt work.
This means that antipsychotics may not be the best treatment to opt for - perhaps some other factor is involved in their apparent success.
A03:One strength of antipsychotics is evidence of their effectiveness.
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 (2012) concluded that clozapine is more effective than typical antipsychotics, and that it is effective in 30-50% of treatment resistant cases.
This means that, as far as we can tell, antipsychotics work.
A03 (counter): David Healy (2012) has suggested serious flaws with evidence for effectiveness.
Most studies are of short term effects only and some data sets have been published several times, exaggerating the size of the evidence base. Also benefits may be due to calming effects of drugs rather than real effects on symptoms.
This means that the evidence of effectiveness is less important than it seems.
