Antipsychotics

Question 1

Give examples of typical (1st generation) antipsychotics

Answer 1

Haloperidol, chlorpromazine, flupentixol, fluphenazine, sulpiride and zuclopenthixol.

Question 2

Give examples of atypical (2nd generation) antipsychotics

Answer 2

Olanzapine, risperidone, quetiapine, amisulpride, aripiprazole and clozapine.

Question 3

According to NICE guidelines, which class of antipsychotics should be first-line?

Answer 3

Atypical (2nd generation) antipsychotics.

Question 4

What are the indications for antipsychotics?

Answer 4

Antipsychotics are indicated for patients suffering from psychotic symptoms such as delusions and hallucinations. They are the mainstay of treatment for schizophrenia.

They can also be used for other conditions when they present with positive psychotic symptoms (e.g. delusions and hallucinations) such as depression,mania ,delusional disorders, acute and transient psychotic disorders, delirium and dementia as well as those with violent or dangerously impulsive behaviour and psychomotor agitation.

Clozapine is licensed as a third-line treatment for schizophrenia and it is the only antipsychotic that has evidence that it is more effective than other antipsychotics.

Question 5

Briefly describe the use of clozapine

Answer 5

Clozapine is licensed as a third-line treatment for schizophrenia and it is the only antipsychotic that has evidence that it is more effective than other antipsychotics.

Clozapine should only be prescribed after failing to respond to two other antipsychotics (treatment-resistant schizophrenia).

Question 6

What receptors do antipsychotics act upon?

Answer 6

Question 7

Briefly differentiate between the mechanism of action of typical and typical antipsychotics

Answer 7

Typical antipsychotics treat psychosis by reducing abnormal transmission of dopamine, through blocking dopamine receptors in the brain.

The mechanism of action of atypical antipsychotics varies, but unlike typical antipsychotics, they have a specific dopaminergic action, blocking the D2 receptor, and they also have serotonergic effects.

Question 8

Briefly describe the treatment of first-episode schizophrenia

Answer 8

Question 9

Which pathways in the brain do antipsychotics work on?

Answer 9

Antipsychotics work on the mesolimbic and mesocortical dopamine pathways to inhibit positive and negative symptoms of schizophrenia, respectively. Antipsychotics cause EPSE via the nigrostriatal pathway and endocrine side effects via the tuberoinfundibular pathway.

Question 10

Which receptors are blocked using antipsychotics that lead to side effects?

Answer 10

One of the main properties of antipsychotics is that they block arousal modulation of EPS memory dopamine receptors, in particular behaviour D2 receptors. However, they also have an affinity for muscarinic, 5HT , histaminergic and adrenergic receptors, which explains their side effect profile.

Question 11

Which class of antipsychotics are extrapyramdial side effects most common in?

Answer 11

Typical antipsychotics.

Question 12

What are the extrapyramdial side effects of antipsychotics?

Answer 12

Extrapyramidal side effects (EPSE) are a major problem especially amongst typical (first generation) antipsychotics. There are four main types of EPSE:

1. Parkinsonism: bradykinesia, ↑ rigidity, coarse tremor, masked facies (expressionless face), shuffling gait. This typically takes weeks or months to occur.
2. Akathisia: unpleasant feeling of restlessness. Occurs in the first months of treatment. It is managed by reducing the dose of antipsychotic and temporarily giving propranolol.
3. Dystonia: acute painful contractions (spasms) of muscles in the neck, jaw and eyes (oculogyric crisis). This can occur within days.
4. Tardive dyskinesia: late onset (years) of choreoathetoid movement (abnormal, involuntary movements). May occur in 40% of patients and may be irreversible. Most commonly presents as chewing and pouting of the jaw.

Question 13

What are the anti-muscarinic side effects of antipsychotics?

Answer 13

‘Can’t see, can’t wee, can’t spit, can’t shit’

Blurred vision, urinary retention, dry mouth and constipation.

Question 14

What are the anti-histaminergic side effects of antipsychotics?

Answer 14

Sedation and weight gain.

Question 15

What are the anti-adrenergic side effects of antipsychotics?

Answer 15

Postural hypotension, tachycardia and ejaculatory failure.

Question 16

What are the endocrine/ metabolic side effects of antipsychotics?

Answer 16

↑ prolactin: sexual dysfunction, reduced bone mineral density, menstrual disturbances, breast enlargement and galactorrhoea.

Impaired glucose tolerance.

Hypercholesterolaemia.

Question 17

Briefly describe neuroleptic malignant syndrome

• Definition
• Epidemiology
• Clinical features

Answer 17

Definition: neuroleptic malignant syndrome is a rare but life-threatening condition seen in patients taking antipsychotic medications. It may also occur with dopaminergic drugs (such as levodopa) for Parkinson’s disease, usually when the drug is suddenly stopped or the dose reduced. E

Epidemiology: carries a mortality of up to 10%. It is more common in young male patients.

Clinical features: onset usually in first 10 days of treatment or after increasing dose. Presents with pyrexia, muscular rigidity, confusion, fluctuating consciousness and autonomic instability (e.g. tachycardia, fluctuating blood pressure). May have delirium.

Question 18

Briefly describe neuroleptic malignant syndrome

• Investigations
• Management
• Complications

Answer 18

Investigations: CK ( ↑ creatinine kinase is usual), FBC (leucocytosis may be seen), LFTs (deranged).

Management: stop antipsychotic, monitor vital signs, IV fluids to prevent renal failure, cooling, dantrolene (muscle relaxant) may be useful in select cases, bromocriptine (a dopamine agonist) may be used, consider benzodiazepines.

Complications: pulmonary embolism, renal failure, shock.

Question 19

What are the cautions for antipsychotics?

Answer 19

Cautions: cardiovascular disease (an ECG may be required), Parkinson’s disease (may be exacerbated by antipsychotics), epilepsy (and other conditions predisposing to seizures), depression, myasthenia gravis, prostatic hypertrophy, susceptibility to angle-closure glaucoma, severe respiratory disease, history of jaundice and blood dyscrasias (perform blood counts if unexplained infection or fever develops).

Question 20

What are the contraindications for antipsychotics?

Answer 20

Contraindications: comatose states, CNS depression and phaeochromocytoma.

Question 21

What parameters need to be monitored for antipsychotic use?

Answer 21

• FBC, U&Es and LFTs
• Fasting blood glucose
• Blood lipids
• ECG
• Blood pressuree
• Prolactin
• Weight
• Physical health
• Creatinine phosphokinase

Question 22

In addition to FBC, U&Es and LFTs, what parameter needs to be assessed when using clozapine?

Answer 22

White blood cell.

Question 23

What antipsychotics are regaular ECGs required in? And why?

Answer 23

ECG monitoring is advised for haloperidol and mandatory for pimozide. Check in particular for prolonged QT interval.

Question 24

Briefly descirbe the advice for stopping antipsychotics

Answer 24

It should be recommended to patients for antipsychotics to be continued for at least 1– 2 years following an episode of psychosis and some recommend continuing for 5 years to prevent relapse.

Patients tend not to adhere to this advice and stop taking antipsychotics much before this. It is therefore essential to take appropriate measures to improve compliance.

If stopping antipsychotics, it is important to advise patients to taper their medication over a period of approximately 3 weeks as opposed to stopping suddenly. The relapse rate in the first 6 months after abrupt withdrawal is double that seen after gradual withdrawal.

Question 25

What is the route of administration for antipsychotics?

Answer 25

The mode of administration of antipsychotics is usually oral.

Some of the antipsychotics can also be given by short-acting intramuscular (IM) injection.

Some antipsychotics can be given as depot injections every 1– 4 weeks.

The patient should be started on the lowest possible dose and then the dose should be titrated to the lowest dose known to be effective. Dose increases should then take place only after 1 or 2 weeks of assessment during which the patient shows poor or no response.

Question 26

Briefly describe the use of depot antipsychotic drugs and why they are used

Answer 26

These are long acting, slow release medications given intramuscularly every 1– 4 weeks.

There are numerous typical antipsychotic depots such as flupentixol, fluphenazine, zuclopenthixol and several atypical (risperidone, olanzapine and aripiprazole).

Depot injections bypass first-pass metabolism.

They are used to improve adherence with medication for patients who may find it difficult to take oral medication regularly.

Question 27

Compare and contrast typical and atypical antipsychotics

• Extrapyramidal side effects
• Tolerability
• Depressive and cognitive symptoms
• Metabolic syndrome
• Weight gain
• Type 2 diabetes
• Stroke in the elderly
• Tardive dyskinesia
• Prolactin levels

Answer 27

Question 28

What are the DO’s when prescribing antipsychotics?

Answer 28

Discuss the benefit and side effect profile with each patient before starting antipsychotics.

Start the patient on the lowest possible dose and then the dose should be titrated.

Perform ECG and bloods before starting on antipsychotic.

Monitor and record the following regularly: efficacy, side effects, adherence, physical health, nutritional status, rationale for continuing, changing or stopping medication.

Consider offering depot/long-lasting injectable antipsychotic medication to avoid non-adherence (intentional or unintentional).

Offer clozapine to people who have not responded adequately to at least two different antipsychotic medications.

Question 29

What are the DON’Ts when prescribing antipsychotics?

Answer 29

Use a loading dose of antipsychotic medication.

Routinely initiate regular combined antipsychotic medication (except for short periods, e.g. when changing medication).

Prescribe antipsychotics without thought in patients with a significant cardiovascular history.

Stop antipsychotics abruptly.