Psychoses and related disorders

Question 1

positive symptoms

Answer 1

hallucinations

delusions

Question 2

negative symptoms

Answer 2

emotional apathy and withdrawal

Question 3

prodromal

Answer 3

characterised by some deterioration in personal functioning and emergence of negative symptoms.

Question 4

acute phase

Answer 4

marked by positive symptoms which may resolve or reduce following treatment, but in some cases negative symptoms can remain and interfere with daily functioning.

Question 5

antiphsychotics are more effective at treating which type of symptoms

Answer 5

positive

Question 6

first line treatment for patients with schizophrenia

Answer 6

An oral antipsychotic drug in combination with psychological therapy should be offered to patients with schizophrenia.

Question 7

choice of drug depends on

Answer 7

factors such as the potential to cause extrapyramidal symptoms (including akathisia),

cardiovascular adverse effects,

metabolic adverse effects (including weight gain and diabetes),

hormonal adverse effects (including increase in prolactin concentration), and

patient and carer preference.

Question 8

how long must a drug to be used to determine effectiveness

Answer 8

titrate low and slow

Patients should receive an antipsychotic drug at an optimum dose for 4–6 weeks before it is deemed ineffective.

Question 9

can more than one antipsychotic be used at once

Answer 9

Prescribing more than one antipsychotic drug at a time should be avoided except in exceptional circumstances (e.g. clozapine augmentation or when changing medication during titration) because of the increased risk of adverse effects such as extrapyramidal symptoms, QT-interval prolongation, and sudden cardiac death. It is important to record the reasons for continuing, changing, and stopping treatment, and the effects of such changes, including side-effects experienced.

Question 10

when should clozapine be offered

Answer 10

Clozapine should be offered if schizophrenia is not controlled despite the sequential use of at least 2 different antipsychotic drugs (one of which should be a second-generation antipsychotic drug), each for an adequate duration. If symptoms do not respond adequately to an optimised dose of clozapine, consider other causes of non-response (e.g. adherence to therapy, concurrent use of other drugs), review diagnosis, and check plasma-clozapine concentration before adding a second antipsychotic drug to augment clozapine; allow 8–10 weeks’ treatment to assess response. Patients must be registered with a clozapine patient monitoring service.

Question 11

first generation antipsychotics

how do they work and examples

Answer 11

The first-generation antipsychotic drugs (also known as typical or conventional) act predominantly by blocking dopamine D2 receptors in the brain. They are more likely to cause a range of side-effects, particularly acute extrapyramidal symptoms and hyperprolactinaemia.

First-generation antipsychotics include the phenothiazine derivatives (chlorpromazine hydrochloride, fluphenazine decanoate, levomepromazine, pericyazine, prochlorperazine, promazine hydrochloride, and trifluoperazine), the butyrophenones (benperidol and haloperidol), the thioxanthenes (flupentixol and zuclopenthixol), the diphenylbutylpiperidines (pimozide) and the substituted benzamides (sulpiride).

Question 12

2nd generation antipsychotics

how do they work and examples

Answer 12

The second-generation antipsychotic drugs (also referred to as atypical) act on a range of receptors in comparison to first-generation antipsychotic drugs and are generally associated with a lower risk for acute extrapyramidal symptoms and tardive dyskinesia; the extent varies between individual drugs. However, second-generation antipsychotic drugs are associated with several other important adverse effects, such as weight gain and glucose intolerance.

Second-generation antipsychotics include amisulpride, aripiprazole, asenapine, cariprazine, clozapine, lurasidone hydrochloride, olanzapine, paliperidone, quetiapine, and risperidone.

Question 13

what is a high dose antipsychotic

Answer 13

total daily dose of a single antipsychotic drug which exceeds the maximum licensed dose with respect to the age of the patient and the indication being treated, and a total daily dose of two or more antipsychotic drugs which exceeds the maximum licensed dose using the percentage method.

Question 14

are high dose antiphsychotics more effective

Answer 14

There is no robust evidence that high doses of antipsychotic drug treatment is any more effective than standard doses for the treatment of schizophrenia. The majority of adverse effects associated with antipsychotic treatment are dose-related and there is clear evidence for a greater side-effect burden with high-dose antipsychotic drug use. Antipsychotic polypharmacy and ‘when required’ antipsychotic drug treatment are strongly associated with high‐dose prescribing.

Question 15

antipsychotic use in the elderly

Answer 15

Antipsychotic drugs should not be used in elderly patients with dementia, unless they are at risk of harming themselves or others, or experiencing agitation, hallucinations or delusions that are causing them severe distress.
The lowest effective dose should be used for the shortest period of time.
Treatment should be reviewed regularly; at least every 6 weeks (earlier for in-patients).

Question 16

Extrapyramidal symptoms

Answer 16

Extrapyramidal symptoms consist of:

parkinsonian symptoms (including bradykinesia, tremor), which may occur more commonly in elderly females or those with pre-existing neurological damage such as stroke, and may appear gradually;
dystonia (uncontrolled muscle spasm in any part of the body), which occurs more commonly in young males; acute dystonia can appear within hours of starting antipsychotics;
akathisia (restlessness), which characteristically occurs within hours to weeks of starting antipsychotic treatment or on dose increase and may be mistaken for psychotic agitation;
tardive dyskinesia (abnormal involuntary movements of lips, tongue, face, and jaw), which can develop on long-term or high-dose therapy, or even after discontinuation; in some patients it can be irreversible.

Question 17

management of tardive dyskinesia

Answer 17

Tardive dyskinesia is the most serious manifestation of late-onset extrapyramidal symptoms for which there is no satisfactory treatment; it occurs more commonly in elderly females. Antipsychotic treatment should be carefully and regularly reviewed; any changes to dose or drug should be made gradually, over weeks or months, to minimise the risk of withdrawal tardive dyskinesia. However, some manufacturers suggest that drug withdrawal at the earliest signs of tardive dyskinesia (fine vermicular movements of the tongue) may halt its full development.

Question 18

Hyperprolactinaemia

Answer 18

Most antipsychotic drugs, both first- and second-generation, increase prolactin concentration to some extent because dopamine inhibits prolactin release.

Aripiprazole reduces prolactin concentration in a dose-dependent manner because it is a dopamine-receptor partial agonist.

Question 19

drugs most likely to cause hyperprolactinaemia

Answer 19

Risperidone, amisulpride, sulpiride, and first-generation antipsychotic drugs are most likely to cause symptomatic hyperprolactinaemia.

Question 20

drugs least likely to cause hyperprolactinaemia

Answer 20

Hyperprolactinaemia is very rare with aripiprazole, asenapine, cariprazine, clozapine, and quetiapine treatment.

Question 21

which drug reduces prolactin concentrations

Answer 21

Aripiprazole reduces prolactin concentration in a dose-dependent manner because it is a dopamine-receptor partial agonist.

Question 22

Sexual dysfunction

Answer 22

Sexual dysfunction is reported as a side-effect of all antipsychotic medication; physical illness, psychiatric illness, and substance misuse are contributing factors. Antipsychotic-induced sexual dysfunction is caused by more than one mechanism. Reduced dopamine transmission and hyperprolactinaemia decrease libido; antimuscarinic effects can cause disorders of arousal; and alpha1-adrenoceptor antagonists are associated with erection and ejaculation problems in men. Risperidone, haloperidol, and olanzapine have a higher prevalence to cause sexual dysfunction. The antipsychotic drugs with the lowest risk of sexual dysfunction are aripiprazole and quetiapine.

Expert sources advise to consider dose reduction or discontinuation (where appropriate), or switching medication if sexual dysfunction is thought to be antipsychotic-induced.

Question 23

drugs that have higher prevalence to cause sexual dysfunction.

Answer 23

Risperidone, haloperidol, and olanzapine have a higher prevalence to cause sexual dysfunction.

Question 24

drugs that have lower prevalence to cause sexual dysfunction.

Answer 24

The antipsychotic drugs with the lowest risk of sexual dysfunction are aripiprazole and quetiapine.

Question 25

Cardiovascular side-effects

Answer 25

Antipsychotic drugs are associated with cardiovascular side-effects such as tachycardia, arrhythmias, and hypotension. QT-interval prolongation is a particular concern with pimozide. Overall risk is probably dose-related but there is also a higher probability of QT-interval prolongation in patients using any intravenous antipsychotic drug, or any antipsychotic drug or combination of antipsychotic drugs with doses exceeding the recommended maximum.

Question 26

Antipsychotic drugs with a low tendency to prolong QT interval include

Answer 26

aripiprazole, asenapine, clozapine, flupentixol, fluphenazine decanoate, loxapine, olanzapine, paliperidone, prochlorperazine, risperidone, and sulpiride.

Question 27

Hypotension

Answer 27

Postural hypotension is a common cardiac side-effect of antipsychotic drugs, usually presenting acutely during the initial dose titration; however, it can also be a chronic problem. Postural hypotension can lead to syncope and dangerous falls related injuries, especially in the elderly. The second-generation antipsychotics most likely to cause postural hypotension are clozapine and quetiapine. Slow dose titration is commonly used to minimise postural hypotension.

Question 28

The second-generation antipsychotics most likely to cause postural hypotension are :

Answer 28

clozapine and quetiapine.

Question 29

lowest risk of diabetes of the antipsychotic drugs.

Answer 29

second-generation
amisulpride and aripiprazole

first generation
fluphenazine decanoate and haloperido

Question 30

are antipsychotics weight neutral, weight loss or weight gaining drugs

Answer 30

weight gain

Question 31

most likely to cause weight gain

Answer 31

Clozapine and olanzapine commonly cause weight gain.

Question 32

least likely to cause weight gain

Answer 32

Amisulpride, asenapine, aripiprazole, cariprazine, haloperidol, lurasidone hydrochloride, sulpiride, and trifluoperazine are least likely to cause weight gain.

Question 33

Neuroleptic malignant syndrome

Answer 33

Neuroleptic malignant syndrome (hyperthermia, fluctuating level of consciousness, muscle rigidity, and autonomic dysfunction with fever, tachycardia, labile blood pressure, and sweating) is a rare but potentially fatal side-effect of all antipsychotic drugs.

Expert sources advise discontinuation of the antipsychotic drug is essential for at least 5 days, preferably longer. The signs and symptoms of neuroleptic malignant syndrome should be allowed to resolve completely. Bromocriptine and dantrolene have been used for treatment.

Question 34

treatment of Neuroleptic malignant syndrome

Answer 34

Bromocriptine and dantrolene have been used for treatment.

Question 35

Long-acting depot injections can be considered for which patients

Answer 35

or patients with psychosis or schizophrenia who prefer such treatment after an acute episode or where avoiding non-adherence to antipsychotic medication is a clinical priority.

Question 36

Antipsychotic depot injections asscoisated with less frequent Extrapyramidal reactions

Answer 36

aripiprazole, paliperidone, risperidone and olanzapine embonate.

Question 37

monitoring requirements

Answer 37

Weight should be measured at the start of therapy with antipsychotic drugs, then weekly for the first 6 weeks, then at 12 weeks, at 1 year, and then yearly.

Fasting blood glucose, HbA1c, and blood lipid concentrations should be measured at baseline, at 12 weeks, at 1 year, and then yearly. Prolactin concentrations should also be measured at baseline.

Before initiating antipsychotic drugs, an ECG may be required, particularly if physical examination identifies cardiovascular risk factors (e.g. high blood pressure), if there is a personal history of cardiovascular disease, or if the patient is being admitted as an inpatient.

Blood pressure monitoring is advised before starting therapy, at 12 weeks, at 1 year and then yearly during treatment and dose titration of antipsychotic drugs.

Expert sources advise to monitor full blood count, urea and electrolytes, and liver function tests at the start of therapy with antipsychotic drugs, and then yearly thereafter.

Question 38

risk of using multiple antipsychotics at once

Answer 38

sudden cardiac death

extrapyramidal effects

Question 39

what should be considered if clozapine therapy of a sufficient dose is ineffective

Answer 39

non adherence

concurrent use of other drugs

Question 40

where must clozapine patients be registered

Answer 40

clozapine patient monitoring service

Question 41

why do 1st gen case more side effects

Answer 41

they are not selective for ant of the 4 dopamine pathways

Question 42

1st gen drugs with higher risk of sedation

Answer 42

chlorpromazine, levomepromazine, promazine

Question 43

1st gen drugs with lowest risk of sedation

Answer 43

haloperidol and benperidol

fluphenazine prochlorperazine, trifluoperazine

Question 44

Higest risk of diabetes

Answer 44

CROQ
CLOZAPINE
RISPERIDONE 
OLANZAPINE 
QUETIAPINE

Question 45

Drugs that cause Qt prolongation

Answer 45

Haloperidol and pizomide