PH3113 Unit 5 Schizophrenia

What is schizophrenia?

A chronic mental disorder affecting thinking, emotion and behaviour

Typical age of onset of schizophrenia?

Late adolescence or early adulthood

What are positive symptoms of schizophrenia?

Hallucinations (often auditory), delusions, disorganised speech and behaviour

What are negative symptoms of schizophrenia?

Avolition (lack of motivation), apathy, social withdrawal, flat affect, poor self-care

What are cognitive symptoms of schizophrenia?

Impaired attention, memory deficits, reduced executive function

What is a delusion?

A fixed false belief not in keeping with reality or cultural background

What is a hallucination?

A perception in the absence of an external stimulus

Most common type of hallucination in schizophrenia?

Auditory

What is the dopamine hypothesis of schizophrenia?

Increased dopamine in mesolimbic pathway = positive symptoms

Decreased dopamine in mesocortical pathway = negative symptoms

Which pathway causes positive symptoms?

Increased dopamine in mesolimbic pathway

Which pathway is linked to negative symptoms?

Decreased dopamine in mesocortical pathway

Why are antipsychotics effective in schizophrenia?

They block dopamine receptors

What is first-line pharmacological treatment for schizophrenia?

Second-generation antipsychotics

Why are SGAs preferred over FGAs?

Lower risk of extrapyramidal side effects and prolactin elevation

When is clozapine used?

Treatment-resistant schizophrenia after failure of two antipsychotics

What are long-acting injections used for?

Improving adherence in schizophrenia

What is the mechanism of action of FGAs?

Potent dopamine D2 receptor antagonists

What is the mechanism of action of SGAs?

Dopamine D2 and serotonin 5-HT2A receptor antagonists

What is the mechanism of action of aripiprazole?

Partial agonist at dopamine D2 , D3 and 5HT1A receptors.

Has both antagonist and agonist action.

Antagonist 5HT2A

Dopamine system stabiliser:

• Antagonists at high DA levels (good for positive symptoms)

• Agonists at low DA levels (good for negative symptoms)

Why are FGAs generally avoided?

High risk of extrapyramidal side effects, hyperprolactinaemia and poor tolerability

What effect do FGAs have on the nigrostriatal pathway?

Cause extrapyramidal side effects

What effect do FGAs have on the tuberoinfundibular pathway?

Increase prolactin levels

What effect do FGAs have on the mesocortical pathway?

May worsen negative symptoms

What are extrapyramidal side effects (EPSE)?

Drug-induced movement disorders due to dopamine blockade

List four types of EPSE

Dystonia, tardive dyskinesia, akathisia, pseudo-parkinsonism

think DTAP (do the anti-psychotics?)

What is dystonia?

Acute involuntary muscle contractions occurring early in treatment (days)

Oculogyric crisis (upward eye movement), torticollis (neck twisting)

How is dystonia treated?

Anticholinergic such as procyclidine

What is akathisia?

Restlessness and inability to stay still

Linked to suicide

How is akathisia treated?

Dose reduction

Beta blockers or benzodiazepines

Avoid anticholinergics

What is tardive dyskinesia?

Late onset involuntary movements such as lip smacking and tongue rolling

How is tardive dyskinesia treated?

Switch antipsychotic if possible

Treat with gradual dose reduction/tetrabenazine (think both start with t)

May not always resolve once withdrawn

Reduce dose of any antimuscarinic (anticholinergics) and stop if possible e.g. procyclidine

How is Pseudo-Parkinsonianism treated? Who is more at risk?

Elderly patients

Treat with anticholinergic e.g. procyclidine

Reduce dose if possible (as dose dependant/% of D2 occupancy)

What is hyperprolactinaemia? What pathway is involved?

Elevated prolactin due to dopamine blockade in tuberoinfundibular pathway

Symptoms of hyperprolactinaemia?

Galactorrhoea (milk production)

Gynaecomastia (enlarged male breasts)

Reduced libido

How can hyperprolactinaemia be treated?

Co-prescribe a low dose of Aripiprazole <5mg alongside FGA/SGA

as it has a partial agonist effect at low DA levels

Which receptor causes sedation and weight gain?

Histamine H1 receptor blockade

Which receptor causes dry mouth and constipation?

Ach Muscarinic receptor blockade

Which receptor causes sedation and hypotension?

Noradrenaline alpha-1 adrenergic receptor blockade

Which receptor effect causes QT prolongation?

Potassium channel blockade

What is Neuroleptic Malignant Syndrome (NMS)?

A life-threatening reaction to antipsychotics with fever, rigidity and confusion

Key features of NMS?

Hyperthermia, rigidity, autonomic disfunction, altered consciousness/confusion

think: TRAC (temp, rigidity, autonomic, confusion)

What should you do if NMS is suspected?

Stop antipsychotic immediately and provide supportive care

What is the main indication for clozapine?

Treatment-resistant schizophrenia

What is the most serious side effect of clozapine?

Agranulocytosis

What is agranulocytosis?

A severe reduction in white blood cells increasing infection risk

How often is FBC monitored with clozapine initially?

Weekly for first 18 weeks

How often is FBC monitored after 1 year of clozapine?

Monthly

What must be done if clozapine causes low neutrophils?

Stop immediately

Common side effects of clozapine?

Sedation, weight gain, hypersalivation, constipation, hypotension

Why is constipation dangerous with clozapine?

Can lead to intestinal obstruction or paralytic ileus

What are other serious risks of clozapine?

Seizures and myocarditis

What physical health checks are required before antipsychotics? (8)

BMI, BP, ECG, glucose, lipids, U&Es, LFTs, prolactin

think: ba-by, go lick ur lovers p (heart)

How often is physical monitoring repeated?

Every 6 to 12 months

Main side effects of olanzapine?

Weight gain and sedation due to histamine H1 antagonisms

Which enzyme metabolises olanzapine?

CYP1A2

How does smoking affect olanzapine and clozapine?

Induces CYP1A2 enzymes

Increased metabolism

Reduces their plasma levels

Higher doses needed when smoking

Dose reduction needed if stopping by monitoring plasma levels before and 7-14 days after cessation

What happens if a patient stops smoking while on olanzapine?

Drug levels increase leading to more side effects

What is a key side effect of risperidone?

Hyperprolactinaemia

What happens at high doses of risperidone?

Acts like an FGA causing EPSE

What are common side effects of quetiapine?

Hypotension, sedation, weight gain

as antagonises alpha-1 adrenoreceptors, histamine, muscarinic

What is unique about aripiprazole’s prolactin effect?

It lowers prolactin

What are advantages of aripiprazole?

Less weight gain, minimal metabolic effects

Why is adherence important in schizophrenia?

Non-adherence leads to relapse and worsening outcomes

What counselling should be given for antipsychotics?

Do not stop abruptly, take regularly, attend monitoring

What lifestyle advice should be given?

Avoid alcohol, stop smoking, healthy diet and exercise

Red flag symptoms to report on antipsychotics?

Fever, severe rigidity, constipation, signs of infection

What SGA are good for people that don’t want metabolic e.g. sedation/weight gain S/Es and why?

Aripiprazole

Amisulpride, Risperidone, Cariprazine, Lurasidone

As less impact on H1/histamine receptors