Psychoses

Question 1

What do antipsychotic medicines do?

Answer 1

Relieve positive psychotic symptoms e.g. thought disorder, hallucinations and delusions and prevent relapse.
Usually less effective on negative symptoms, such as apathy and social withdrawal

Question 2

Mechanism of action of first generation antipsychotics

Answer 2

Block dopamine D2 receptors in the brain. Not selective for any of the four dopamine pathways so can cause range of side effects, including EPSE and elevated prolactin.

Question 3

Types of 1st gen antipsychotics

Answer 3

Phenothiazine derivatives:

GROUP 1- chlorpromazine, levomepromazine, promazine
Pronounced sedative effects, moderate antimuscarinic and EPSE

GROUP 2- pericyazine
Moderate sedative effects, fewer EPSE than groups 1+3

GROUP 3- fluphenazine, perphenazine, prochlorperazine, trifluoperazine
Fewer sedative effects and antimuscarinic effects but more pronounced EPSE

Butyrophenones- benperidol and haloperidol (like the Group3 phenothiazines)
Thioxanthenes- flupentixol and zuclopenthixol- moderate sedative, antimuscarinic and EPSE
Diphenylbutylpiperidines- pimozide- and the substituted benzamides- sulpiride- have reduced sedative effects, moderate antimuscarinic and EPSE.

Question 4

Antipsychotic medicines in elderly

Answer 4

Elderly patients with dementia- increased risk of mortality, stroke or TIA
Initial doses should be reduced
Wary of hypotension and hypo/hyperthermia

Question 5

Extrapyramidal side effects

Answer 5

Parkinsonian symptoms- including tremor
Dystonia- abnormal face and body movements
Dyskinesia
Akathesia (restlessness)
Tardive dyskinesia (rhythmic, involuntary movements of the jaw, tongue or face) This may occur after withdrawal of the drug and may be irreversible.

Question 6

Why does hyperprolactinaemia occur?

Answer 6

Dopamine inhibits prolactin release so increase in prolactin concentration occurs in first and second gen antipsychotics to some extent.

Question 7

Aripiprazole

Answer 7

Reduces prolactin as it is a partial agonist of the dopamine receptor
Negligible effect on QT interval

Question 8

Which antipsychotics are most likely to cause hyperprolactinaemia?

Answer 8

Risperidone
Amisulpride
First gen antipsychotics

Question 9

Symptoms of hyperprolactinaemia

Answer 9

Sexual dysfunction
Reduced bone mineral density
Menstrual disturbances
Breast enlargement
Galactorrhoea

Question 10

Causes of sexual dysfunction

Answer 10

Reduced dopamine and hyperprolactinaemia- reduce libido
Antimuscarinic effects- disorders of arousal
Alpha- adrenoceptor antagonists- erection and ejaculation problems in men

Question 11

Antipsychotics that commonly cause sexual dysfunction in men

Answer 11

Risperidone

Haloperidol

Question 12

Cardiovascular side effects with antipsychotics

Answer 12

Tachycardia, arrhythmias and hypotension

Question 13

Which antipsychotics are more likely to cause QT prolongation?

Answer 13

Pimozide and haloperidol

Also more likely with intravenous use

Question 14

Which antipsychotics commonly cause hyperglycaemia and sometimes diabetes?

Answer 14

Clozapine
Olanzapine
Risperidone
Quetiapine

Question 15

Which antipsychotics commonly cause weight gain?

Answer 15

All antipsychotics may cause weight gain but clozapine and olanzapine do more commonly.

Question 16

Which antipsychotics may cause postural hypotension?

Answer 16

Clozapine
Chlorpromazine
Lurasidone
Quetiapine

Question 17

What is neuroleptic malignant syndrome?

Answer 17

Rare but potentially fatal side effect of all antipsychotics
Discontinuation essential
Bromocriptine and dantrolene have been used for treatment
Usually lasts for 5-7 days after drug discontinuation but can be worsened if depot preparations are used.

Question 18

Symptoms of neuroleptic malignant syndrome

Answer 18

Hyperthermia
Fluctuating level of consciousness
Muscle rigidity
Autonomic dysfunction with pallor
Tachycardia
Labile blood pressure
Sweating 
Urinary incontinence

Question 19

Negative symptoms of schizophrenia

Answer 19

Second gen antipsychotics may be better at treating the negative symptoms.

Question 20

Which pathway is responsible for extra pyramidal side effects?

Answer 20

Blockade of the striatal dopamine pathway

Question 21

Of the second gen antipsychotics, which are least likely to cause EPSE?

Answer 21

Clozapine
Olanzapine
Quetiapine
Amisulpride

Question 22

Schizophrenia and diabetes

Answer 22

Schizophrenia is associated with insulin resistance and diabetes.
First gen are less likely to cause diabetes than second gen.

Question 23

Which antipsychotics are least likely to cause diabetes?

Answer 23

1st gen- Fluphenazine + Haloperidol

2nd gen- Amisulpride + Aripiprazole

Question 24

Antipsychotics with the lowest risk of sexual dysfunction

Answer 24

Aripiprazole and quetiapine

Question 25

In which antipsychotics is hyperprolactinaemia not significant?

Answer 25

Aripiprazole
Clozapine
Olanzapine
Quetiapine

Question 26

When should clozapine be introduced?

Answer 26

If schizophrenia is not controlled despite use of two or more antipsychotics (one of which should be a 2nd gen), each for at least 6-8 weeks.

Question 27

How long should clozapine be monitored for before augmenting with a second antipsychotic drug?

Answer 27

8-10 weeks

Question 28

Monitoring of antipsychotics

Answer 28

Before initiation and annually:
FBC
U&Es
LFTs
Blood lipids and weight: baseline, 3 months and annually
Fasting blood glucose: baseline, 4-6 months and annually
ECG prior to initiation
BP check advised
Prolactin: baseline, 6 months and annually

Question 29

When is there a high risk of relapse?

Answer 29

If medication is stopped after 1-2 years

Monitor for 2 years after stopping meds.

Question 30

Photosensitisation with antipsychotics

Answer 30

May occur at higher doses so avoid direct sunlight

Question 31

Which antipsychotics are given for intractable hiccups?

Answer 31

Chlorpromazine

Haloperidol

Question 32

Dosing of aripiprazole

Answer 32

Concurrent use of CYP3A4 inducers: double dose

Concurrent use of CYP3A4 inhibitors: halve dose

Question 33

Clozapine MHRA alert

Answer 33

Potential risk of intestinal peristalsis (intestinal obstruction, faecal impaction and paralytic ileus)

Question 34

Cautions for clozapine

Answer 34

> 60 years
Prostatic hypertrophy
Susceptibility to angle closure glaucoma
Neutropenia and potentially fatal agranulocytosis- measure leucocytes and differential blood counts
Myocarditis (most common in first 2 months) and cardiomyopathy (persistent tachycardia may be an indicator)
Intestinal obstruction

Question 35

Hypersalivation with clozapine

Answer 35

Can be treated with hyoscine (unlicensed)- as long as patient isn’t at risk from the additive antimuscarinic side effects

Question 36

Statins in pregnancy

Answer 36

Statins should be avoided in pregnancy (discontinue 3 months before attempting to conceive) as congenital anomalies have been reported and the decreased synthesis of cholesterol possibly affects fetal development.
Adequate contraception is required during treatment and for 1 month afterwards.

Question 37

Monitoring of clozapine

Answer 37

Leucocyte and differential blood counts- every week for first 18 weeks, then every 2 weeks. If blood count stable after 1 year, every 4 weeks (and 4 weeks after discontinuation).Discontinue permanently if leucocyte count <3000/mm3 or if absolute neutrophil count <1500/m3 and refer.
LFTs- Discontinue if liver enzymes are greater than 3 times the upper limit of normal or if jaundice occurs.
Blood lipids and weight- every 3 months for the first year, then annually.
Fasting blood glucose- baseline, at 4-6 months, then yearly

Question 38

Treatment cessation of clozapine

Answer 38

Reduce dose over 1-2 weeks to avoid risk of rebound psychosis.

Question 39

Monitoring in intramuscular olanzapine

Answer 39

Blood pressure, pulse and respiratory rate for at least 4 hours after injection, especially in those also receiving a benzodiazepine or another antipsychotic.
Leave at least 1 hour between olanzapine IM and parenteral benzodiazepine.