biological therapies: drug therapy

antipsychotics

drugs used to reduce the intensity of symptoms, in particular the positive symptoms of psychotic conditions like sch

can be taken as tablets or syrup, for those particularly at risk of failing to take their meds regularly, some are injections given every 2-4 weeks

typical antipsychotics

the first generation of antipsychotic drugs, having been used since the 50s, they work as dopamine antagonists and include chlorpromazine

atypical antipsychotics

drugs for sch developed after typical antipsychotics. they typically target a range of neurotransmitters such as dopamine and serotonin. examples include clozapine and risperidone

when do people use antipsychotics

they may be required in the short or long term. some people with schizophrenia 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 recurrence

chlorpromazine

can be taken as tablets, syrup or injection. if taken orally it’s administered daily up to a max of 100mg, though initial doses are much smaller and for most people it gradually increases to a max of 400-800mg

Liu and Haan

typical prescribed doses of chlorpromazine have declined over the last 50 years

how typical antipsychotics work

chlorpromazine works by acting as an antagonist in the dopamine system. dopamine antagonists block dopamine receptors in the synapses of the brain, reducing the action of dopamine

initially when a patient begins taking it, dopamine levels build up but then its production is reduced. according to the dopamine hypothesis, this dopamine-antagonist effect normalises neurotransmission in key areas of the brain, reducing symptoms like hallucinations

sedative effect of chlorpromazine

believed to be related to its effect on histamine receptors but not fully understood how this leads to sedation. chlorpromazine’s often used to calm people not only with sch but other conditions. this has been done when people are first admitted to hospitals and are very anxious. syrup is absorbed faster than tablets so tends to be used for sedative properties

aim of atypical antipsychotics

maintain or improve upon the effectiveness of drugs in suppressing the symptoms of psychosis and also to minimise the side effects. there a range of atypical antipsychotics and they don’t all work in the same way, we don’t know how some of them work

clozapine

developed in 60s and first trailed in early 70s, withdrawn for a while in 70s after the deaths of some users from a blood condition called agranulocytosis but in the 80s it was found to be more effective than typical ones so it was remarketed to be used when other treatments failed

now people have regular blood tests. because of the potentially fatal side effect it’s not typically available as an injection. it has a lower daily dosage of 300-450mg a day

how clozapine works

it binds to dopamine receptors in the same way chlorpromazine does but also acts on serotonin and glutamate receptors. believed this action helps improve mood and reduce depression and anxiety so may improve cognitive functioning

mood-enhancing effect means it’s sometimes prescribed when someone is at high risk of suicide. important as 30-50% of people with sch attempt suicide

risperidone

more recently developed in 90s. developed to produce a drug as effective as clozapine but without the side effects. can be taken as tablets, syrup or injection which lasts around 2 weeks. initially a small dose is given which is built up to a typical daily dose of 4-8mg and a max of 12mg

how risperidone works

it’s believed to bind to dopamine and serotonin receptors. it binds more strongly to dopamine receptors than clozapine and is therefore effective in much smaller doses than most antipsychotics. there’s some evidence to suggest this leads to fewer side effects than is typical for antipsychotics

Thornley et al.

reviewed studies comparing the effects of chlorpromazine to control conditions in which people with sch received a placebo so their experiences were identical except for the presence of chlorpromazine in their meds. data from 13 trials with 1121 pps showed chlorpromazine was associated with better overall functioning and symptom severity.

data from 3 trials with 512 pps showed relapse rate was lower when chlorpromazine was taken

Meltzer

concluded that clozapine is more effective than TAP and other AAP and it’s effective in 30-50% of treatment-resistant cases where TAP have failed

effectiveness of clozapine

a number of studies have compared its effectiveness and other AAP like risperidone but results have been inconclusive, perhaps some people respond better to one drug or the other

in general antipsychotics are reasonably effective which is a strength

side effects of typical antipsychotics

includes dizziness, agitation, sleepiness, stiff jaw, weight gain and itchy skin

long-term use can result in tardive dyskinesia which is caused by dopamine supersensitivity and manifests as involuntary facial movements like grimacing, blinking and lib smacking

neuroleptic malignant syndrome NMS

the most serious side effect of TAP. it’s believed to be caused because the drug blocks dopamine action in the hypothalamus, an area of the brain associated with the regulation of a number of body systems

it results in high temp, delirium and coma and can be fatal. as typical doses of antipsychotics have declined, NMS has become rarer. estimates of its frequency range from less than 0.1% to just over 2%

side effects of atypical antipsychotics

they were developed to reduce the frequency of side effects and generally this has succeeded - Meltzer

however, side effects still exist and people taking clozapine have to have regular blood tests to alert doctors to early signs of agranulocytosis so side effects are still a significant weakness of antipsychotics

antipsychotics and the dopamine hypothesis

dopamine hypothesis is the idea that there are higher than usual levels of dopamine activity in the subcortex. but there’s evidence to show this isn’t a complete explanation of sch and dopamine levels in parts of the brain other than the subcortex are too low rather than too high

if this is true it’s not clear how antipsychotics which are dopamine antagonists can help with sch when they reduce dopamine activity

modern understanding of relationship between dopamine and psychosis suggests antipsychotics shouldn’t work which has undermined faith in them

Healy

suggested some successful trials have had their data published multiple times, exaggerating evidence for positive effects

because antipsychotics have powerful calming effects, it’s easy to demonstrate they have some positive effect on people with sch but may not actually reduce psychosis

most published studies assess short-term benefits rather than long-term and compare people who keep taking antipsychotics with those experiencing withdrawal having just stopped taking them

the chemical cosh argument

widely believed antipsychotics have been used in hospital situations to calm people and make them easier for staff to work with rather than for the benefit of the patients

although short-term use of antipsychotics to calm agitated people is recommended by the NICE which is seen by some as human rights abuse - Moncrieff