Advanced Mental Health

Define psychosis?

cluster of symptoms mainly focussed particularly around delusions and hallucinations

What other conditions can antipsychotics be used in?

bipolar affective disorder, depression with psychosis and acutely aggressive/violent behaviour requiring sedation

What is the simplified pharmacology of antipsychotics?

excess dopamine in the brain, particularly in the mesolimbic pathway, results in psychotic experiences

Most block dopamine receptors

What are the main side effects of first generation antipsychotics?

extra-pyramidal side effects such as parkinsonism, akathisia, dystonia and tardive dyskinesia

What are the main side effects of second generation antipsychotics?

less likely to cause extrapyramidal but have other risks such as metabolic side-effects

Which set of symptoms improved most with antipsychotics?

Positive symptoms improved more than negative and affective ones

Why are their concerns about practice that depends on diagnostic classification?

• Disagreement regarding the validity and usefulness of psychiatric diagnoses

• Scepticism about the efficacy of anti-depressants, mood stabilisers and anti-psychotic agents and concerns about their dangers

Why is clozapine significantly different to other antipsychotics?

• Greater D1/D4 antagonism than D2/D3

• Also 5-HT2a/2c antagonist

What is the main grave side effect of clozapine?

Agranulocytosis → wiping out white blood cell production and people dying of very severe infections

Before starting clozapine what needs to be checked?

Review adherence, diagnosis, non-pharmacological treatments, co-morbidities etc.

What is clozapine licensed for?

treatment resistant schizophrenia

What are the conditions for clozapine?

No improvement on two different antipsychotic agents, including an atypical antipsychotic agent included intolerable side effects

When can patients start clozapine treatment?

After 16 weeks of unsuccessful treatment
Most wait 2 to 5 years

Why can waiting to start clozapine be detrimental?

• Episodes of acute illness may cause damage that may be difficult to reverse

• More episodes harder to get back to original level of functioning

What are the main adverse effects of clozapine?

Agranulocytosis

Metabolic

Cardiac → myocarditis
Constipation
Sedation
Seizures
Hypersalivation
Risk of pneumonia

What monitoring needs to be done for clozapine?

FBC monitoring as required by the monitoring service + plasma level monitoring
proactive assessment of side effects
Drug and interactions such as smoking
Metabolic side effects
Education of all staff bout monitoring needed
Need to work with patients

What are the expected trough levels of clozapine?

Narrow therapeutic range

0.35 to 0.6 mg/L
Need treatment 10-14 days

What is clozapine plasma clearance affected by?

sex, ethnicity, smoking status and body weight, amongst other factors

How does smoking affect clozapine dosing?

Clozapine metabolised by CYP1A2, CYP3A4 to form metabolite N-desmethylclozapine (norclozapine)
CYP1A2 induced by tobacco smoke
Average clozapine dose for smoker increase by 30%

When does clozapine need re-titration?

After 48hrs