L4 - Drug Therapy

Question 1

Define antipsychotics

Answer 1

Drugs used to reduce the intensity of symptoms, in particular the positive symptoms, of psychotic conditions like schizophrenia.

Question 2

What can antipsychotics be divided into?

Answer 2

Typical (traditional) or atypical (newer, second-generation).

Question 3

When were typical antipsychotics developed?

Answer 3

1950s.

Question 4

Give an example of a typical antipsychotic?

Answer 4

Chlorpromazine.

Question 5

What methods can chlorpromazine be taken in?

Answer 5

Tablets, syrup or injection.

Question 6

What is the average maximum dose administered of chlorpromazine if taken orally daily?

Answer 6

Initial doses smaller so generally increased to a maximum of 400-800mg but can be up to 1000mg.

Question 7

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

Answer 7

Liu and de Haan (2009)

Question 8

What are antagonists?

Answer 8

Chemicals which reduce the action of a neurotransmitter

Question 9

What happens when an individual takes chlorpromazine in terms of dopamine level?

Answer 9

Initially dopamine levels build up, but production is eventually reduced

Question 10

What can typical anti psychotics be known as?

Answer 10

Dopamine antagonists

Question 11

How do dopamine antagonists work?

Answer 11

By blocking dopamine receptors in the synapses of the brain, reducing the action of dopamine

Question 12

What happens according to the dopamine hypothesis of schizophrenia?

Answer 12

The dopamine antagonist effect normalises neurotransmission in key areas of the brain, reducing symptoms like hallucinations.

Question 13

What other effect can chlorpromazine have and why?

Answer 13

A sedative effect potentially due to its effects on histamine receptors.

Question 14

How else can chlorpromazine be used?

Answer 14

To sedate those with schizophrenia and other conditions, often when they first are admitted to hospital and are very anxious.

Question 15

What form is chlorpromazine given in when used as a sedative?

Answer 15

Syrup as it is absorbed easier.

Question 16

When were atypical antipsychotics introduced?

Answer 16

1970s.

Question 17

What was the aim of developing newer antipsychotics?

Answer 17

To maintain or improve upon the effectiveness of drugs in suppressing the symptoms of psychosis and also minimise the side effects of the drugs used.

This goal addresses both the efficacy and safety of antipsychotic medications.

Question 18

Give two examples of an atypical antipsychotic.

Answer 18

• Clozapine
• Risperidone

Atypical antipsychotics are known for their different pharmacological profiles compared to typical antipsychotics.

Question 19

When was Clozapine developed and trialled?

Answer 19

Developed in the 1960s and trialled in the 1970s.

Clozapine was one of the first atypical antipsychotics.

Question 20

Why was Clozapine withdrawn from the market in the 1970s?

Answer 20

Deaths of some patients from a blood condition called agranulocytosis.

Agranulocytosis is a serious side effect that involves a dangerously low level of neutrophils in the blood.

Question 21

How was Clozapine remarketed in the 1980s after discovering it worked better than typical antipsychotics?

Answer 21

Remarketed as a treatment for schizophrenia when all other treatments failed due to fatal side effects.

This change in marketing strategy highlighted its effectiveness in treatment-resistant cases.

Question 22

How are side effects of Clozapine managed?

Answer 22

Regular blood tests to ensure they aren’t developing agranulocytosis

Clozapine is not available as an injection.

Question 23

What is the average daily dosage of Clozapine?

Answer 23

300-450mg a day

Question 24

How does Clozapine work?

Answer 24

Binds to dopamine receptors and acts on serotonin and glutamate receptors

This improves mood and reduces depression and anxiety in patients, possibly improving cognitive functioning.

Question 25

What do the mood enhancing effects of Clozapine mean?

Answer 25

They may improve cognitive functioning

Question 26

When was Risperidone developed?

Answer 26

1990s

Question 27

Why was Risperidone developed?

Answer 27

In an attempt to produce a drug as effective as clozapine but without its serious side effects

Question 28

True or False: Patients that are high-risk for suicidal tendencies are often prescribed Clozapine.

Answer 28

True

Question 29

Fill in the blank: _______ is a medication that may improve cognitive functioning in patients.

Answer 29

Clozapine

Question 30

How can Risperidone be administered?

Answer 30

Risperidone can be administered as a tablet, syrup, or injection which lasts 2 weeks.

Question 31

What is the dose of Risperidone?

Answer 31

The initial dose is small and built up to a typical daily dose of 4-8mg, with a maximum of 12mg.

Question 32

How does Risperidone work?

Answer 32

Risperidone binds to dopamine and serotonin receptors, binding stronger to dopamine receptors than Clozapine.

Question 33

Discuss the strength of evidence for effectiveness of typical antipsychotics.

Answer 33

Thornley et al. (2003) found chlorpromazine associated with better overall functioning and reduced symptom severity than a placebo based on data from 13 trials with a total of 1121 participants.

Question 34

Discuss the strength of evidence for effectiveness of atypical antipsychotics.

Answer 34

Meltzer (2012) concluded Clozapine is more effective than typical and other atypical antipsychotics, effective in 30-50% of treatment-resistant cases where typical antipsychotics have failed.

Question 35

What did Healy (2012) suggest about the strength of evidence for effectiveness?

Answer 35

Healy suggested serious flaws in evidence, noting that most studies are short-term and some data has been published multiple times, exaggerating the size of the evidence base for positive outcomes. ## Footnote Healy also mentioned that while there may be a calming effect, this does not equate to a reduction in psychosis.

Question 36

What are some serious side effects associated with typical antipsychotics?

Answer 36

Typical antipsychotics are associated with side effects such as dizziness, agitation, sleepiness, stiff jaw, weight gain, and itchy skin. ## Footnote Long-term use can lead to tardive dyskinesia, which is caused by dopamine supersensitivity and results in involuntary facial movements.

Question 37

What is neuroleptic malignant syndrome (NMS) and its seriousness?

Answer 37

NMS is a serious condition caused when the drug blocks dopamine action in the hypothalamus, resulting in high temperature, delirium, and coma, which can be fatal. Estimates of its frequency range from 0.1-2%.

Question 38

What is a limitation of the original dopamine hypothesis in understanding antipsychotic drug mechanisms?

Answer 38

The original dopamine hypothesis does not provide a complete explanation for schizophrenia.

Question 39

What do we now know about dopamine levels in relation to schizophrenia?

Answer 39

Dopamine levels in some areas of the brain are too low rather than high.

Question 40

If the original dopamine hypothesis were true, what would be expected regarding the effectiveness of most antipsychotics?

Answer 40

Most antipsychotics shouldn't work.