Psychosis and Schizophrenia

What were antipsychotics formerly called?

Major tranquillisers / Neuroleptics

What therapeutic effects can antipsychotics have?

• Anxiolytic

• Antimanic

• Mood stabilising

• Antidepressant

What are the main indications of antipsychotics

• Schizophrenia

• Bipolar disorder

• Severe anxiety and depression

What are positive symptoms?

• Delusions

• Hallucinations

• Disorganisation

What are negative symptoms?

• Social withdrawal

• Neglect

• Poor hygiene

What is the prodromal phase?

Early deterioration with emerging negative symptoms

What is the acute phase?

Follows the prodromal phase Dominated by positive symptoms

Long-term course of schizophrenia

• Positive symptoms may resolve

• Negative symptoms may persist

Initial treatment aim in schizophrenia

Reduce acute symptoms and restore baseline function

Why is maintenance therapy needed?

Prevent relapse

Are antipsychotics more effective for positive or negative symptoms?

Positive symptoms

Psychosis treatment

• Oral antipsychotic

• CBT

Factors affecting drug choice

• Metabolic effects

  • weight gain and diabete

• Extrapyramidal symptoms

  • akathisia, dyskinesia and dystonia

• Hormonal effects (prolactin)

• Patient/carer preference

How should antipsychotics be started?

• Low dose

• Slow titration

How long before judging effectiveness?

4–6 weeks

Should antipsychotic polypharmacy be used?

Avoid except exceptional cases

Risks of combining antipsychotics

• EPS

• QT prolongation

• Sudden cardiac death

What must be documented during treatment?

• Reasons for changes

• Effects

• Side effects

Mechanism of first-gen antipsychotics

Dopamine D2 receptor blockade

Key characteristic of first-gen drugs

More extrapyramidal side effects

Examples of phenothiazines

• Chlorpromazine

• Levomepromazine

• Promazine

• Pericyazine

• Fluphenazine

• Prochlorperazine

• Trifluoperazine

Examples of butyrophenones

Haloperidol, Benperidol

Examples of thioxanthenes

Flupentixol, Zuclopenthixol

Other first-gen antipsychotics

Pimozide, Sulpiride

Key pharmacological feature of second-gen antipsychotics (atypical)

Act on multiple receptors → compared to first generation

Main advantage of Second Generation (Atypical)

Lower EPS risk

Main disadvantage of Second Generation (Atypical)

Metabolic effects (weight gain, diabetes, lipid changes)

Examples of second-gen antipsychotics

• Amisulpride

• Aripiprazole

• Clozapine

• Risperidone

• Olanzapine

• Quetiapine

• Asenapine

• Lurasidone

• Paliperidone

What Causes of EPS

D2 blockade in nigrostriatal pathway

Which drugs cause have very low EPS risk?

• Olanzapine

• Clozapine

• Quetiapine

• Aripiprazole

Types of EPS Parkinsonism features

Bradykinesia, tremor
May appear gradually

Who is at higher risk of Parkinsonism?

Elderly females, neurological damage

Types of EPS What is dystonia?

Uncontrolled muscle spasms
Can appear within hours of starting medication

Who gets dystonia more?

Young males

What is akathisia?

Restlessness

Usually hours to weeks of starting or dose increase

mistaken for psychotic agitation

What is tardive dyskinesia?

Involuntary facial/tongue movements
Usually long term and high dose therapy even after discontinuation

Common in elderly females

Key feature of tardive dyskinesia

May be irreversible

Management of Parkinsonism

• Reduce dose → high potency high dose

• Switch drug

• Use antimuscarinics (not prophylaxis)

Management principle for tardive dyskinesia

Gradual dose changes
Dose or drug changes should be gradual

When does postural hypotension occur?

During dose titration however can be a chronic problem

Which antipsychotics most likely to cause hypotension?

Second Gen

• Aripiprazole

• Risperidone

• Clozapine

• Quetiapine

• ARCQed posture

How to combat postural hypotension?

Gradual dose titration

Which drug causes hypertension?

Clozapine

Drug strongly linked to QT prolongation

Pimozide
Dose related

Combination therapy

High-risk drugs for diabetes

• Risperidone

• Olanzapine

• Quetiapine

• Clozapine

• ROQ-C

Lowest diabetes risk drugs

• Haloperidol

• Fluphenazine

• Aripiprazole

• Amisulpride

Drugs causing most weight gain

Olanzapine, Clozapine
WOC

Why do antipsychotics increase prolactin?

Dopamine normally inhibits prolactin

Drugs that DO NOT increase prolactin

• Clozapine

• Olanzapine

• Quetiapine

• Aripiprazole

• No (COQA)

Symptoms of hyperprolactinaemia

• Sexual dysfunction

• Menstrual disturbance

• Galactorrhoea

• Breast enlargement

• Reduced bone density

Causes of sexual dysfunction

• Reduced dopamine

• Hyperprolactinaemia

• Antimuscarinic effects

• Alpha-1 blockade

High risk to cause sexual dysfunction?

• Risperidone

• Haloperidol

• Olanzapaine

low risk to cause sexual dysfunction?

• Aripiprazole

• Quetiapine

Features of Neuroleptic Malignant Syndrome

• Hyperthermia

• Rigidity

• Altered consciousness

• Autonomic instability

• Fever

• Tachycardia

Management of Neuroleptic Malignant Syndrome

• Stop antipsychotic ≥5 days

• Supportive care

• Bromocriptine/Dantrolene

• Signs and symptoms need to resolve completely

What is Neuroleptic malignant syndrome?

is a rare but potentialy fatal side effect of all antipsychotic drugs

Key interacting drug groups

• Sedatives

• Hypotensives

• QT-prolonging drugs

• CYP450 modulators

Effect of smoking

Decreases Olanzapine & Clozapine levels
Increased adverse effects when stop smoking

Weight monitoring schedule

Start, weekly (6 weeks), 12 weeks, 1 year, yearly

When does Glucose/HbA1c monitoring, blood concentrations, BP need to happen?

Start, 12 weeks, yearly

ECG monitoring

Before starting
Especially those with cardiac risk factors

When and what Blood tests monitoring

FBC, U&E’s, eGFRs and LFTs

Start, yearly

Prolactin monitoring

6 months, then yearly

Why use depot injections?

Improve adherence → clinical priority

Which depots have more side effects?

First-gen depots to higher incidence of EPS

What defines high-dose antipsychotic use?

Above licensed dose or combined excess

Risk of high-dose therapy

Increased adverse effects

Risk of antipsychotics in the elderly

Increased mortality and stroke
Postural hypotension

When to use antipsychotics in dementia?

• Risk of harm

• Severe distress

In Learning Disabilities What should be considered if no psychosis?

• Reduce/stop drug

• Review

• Specialist referral

When can clozapine be used?

Only use when 2+ antipsychotics including one 2nd generations has been used for an adequate period of time

Clozapine monitoring schedule

• Weekly (18 weeks)

• Fortnightly (1 year)

• Monthly

• Til 4 weeks after discontinuation

Leukocytes and differential blood counts

Blood side effects of clozapine

Agranulocytosis, Thrombocytopenia

Cardiac risks of clozapine

Myocarditis, cardiomyopathy

Report and stop on tachycardia at rest

GI risk of clozapine

Paralytic ileus

Other risks of clozapine

• Seizures

• MI

• QT prolongation

• Thromboembolism

• Fever

• NMS

• Hyperglycaemia

• Weight gain

What increases clozapine toxicity?

• Stopping smoking

• Infection

Special requirement for clozapine

Patient monitoring service registration

High risk of sedation

Clozapine, Chlorpromazine

Very low risk of sedation

Amisulpride

Aripiprazole

High risk of EPSE

Haloperidol

Zuclopenthixol

Very Low EPSE risk

Clozapine

High anticholinergic burden

Clozapine

Very Low anticholinergic burden

Amisulpride

Aripiprazole

High risk QT prolongation

Haloperidol Pimozide

Very low risk QT prolongation

Aripiprazole Zuclopenthixol

Drugs that cause stroke

• Risperidone

• Olanzapine

  • STROKE

Prescribing in dementia?

Lowest effective dose
Review at least every 6 weeks

Clozapine MHRA warning

Monitor for toxicity if

Patient stops smoking/switches to e-cigarette

• Patient has pneumonia or other serious infection

• Other risks of toxicity

If symptoms do not resolve

Adherence
Other drugs

Review diagnosis → check plasma clozapine before adding second antipsychotic in

Clozapine Pregnancy and BF

Caution in pregnancy

Avoid in BF