Antipsychotics

Question 1

What are the indications for use of antipsychotics?

ie what conditions are they used to treat

Answer 1

Schizophrenia

Schizoaffective disorder

Bipolar disorder:

(for mood stabilisation and/or when psychotic features are present)

Psychotic depression

Resistant depression (augmenting agent)

Resistant anxiety (augmenting agent)

Question 2

What chemical in le brain do antipsychotics affect?

Answer 2

Dopamine

Antagonists - so reduce the amount of dopamine in certain pathways of the brain

Question 3

What are the key dopamine pathways in the brain?

Answer 3

Mesocortical

Mesolimbic

Nigrostriatal

Tuberoinfundibular

Question 4

What is the mesocortical dopamine pathway?

What abnormality causes psychotic symptoms?

Answer 4

Mesocortical

• ventral tegmentum (brainstem) to the cerebral cortex
• This pathway is felt to be where the negative symptoms and cognitive disorders (lack of executive function) arise
• this is due to too little dopamine

Question 5

What is the Mesolimbic pathway?

What abnormalities cause psychosis?

Answer 5

Mesolimbic

• dopaminergic cell bodies in the ventral tegmentum (brainstem) to the limbic system
• Too much dopamine is responsible for positive symptoms of psychosis (hallucinations, delusions, disordered thought)

Question 6

What is the Nigrostriatal pathway?

In a healthy patient - what is this pathway involved in?

What abnormalities does abnormal dopamine levels cause?

Answer 6

Nigrostriatal

• dopaminergic cell bodies of substantia nigra (midbrain/mesencephalon) to the basal ganglia
• Involved in movement regulation -using ACh (which dopamine suppresses)
• Dopamine hypoactivity (when treating with antipsychotics) can impact movement regulation - which leads to Parkinsonian movements

Question 7

Dopamine hypoactivity in the Nigrostriatal pathway can lead to dysfunctional movement regulation

What would you see in a patient with this dyregulation?

Answer 7

Parkinsonian movements (extrapyramidal side effects)

Rigidity

Bradykinesia

Tremors

Akathisia (restless legs)

Dystonia

Question 8

What is the tuberoinfundibular pathway?

What side effects can be seen when blocking dopamine that are linked to this pathway?

Give the specific features of this

Answer 8

Tuberoinfundibular

• hypothalamus to anterior pituitary
• antipsychotic use (blocking dopamine) in this pathway predisposes patients to hyperprolactinaemia:

gynecomastia

galactorrhea

decreased libido

menstrual dysfunction

Question 9

What are the groups of antipsychotics?

What are the subgroups and some exampled of eacg

Answer 9

Typical & Atypical

Typical - D2 receptor antagonists

Atypical - serotonin-dopamine 2 antagonists (SDAs)

Question 10

What are the types of Typical antipsychotics?

Give some examples

What side effects are associated with each type?

Answer 10

Typical antipsychotics

1) High potency - high affinity for D2:

• associated w/ extrapyramidal side effects (parkinsonian)
• Eg - Fluphenazine, Haloperidol, Pimozide

2) Low potency - lower affinity for D2:

• associated w/ cardiotoxic and anticholinergic adverse effects including sedation, hypotension
• Eg - chlorpromazine and thioridazine

Question 11

The Atypical Antipsychotics are serotonin-dopamine 2 antagonists (SDAs)

Which pathways do they affect in the brain?

Answer 11

Affect sertonin and dopamine neurotransmission in all 4 of the key dopamine pathways:

• Mesocortical
• Mesolimbic
• Nigrastriatic
• Tuberoinfundibular

Question 12

What are the main atypical antipsychotics?

Answer 12

Risperadone - (Risperdal)

Olanzapine - (Zyprexa)

Quetiapine - (Seroquel)

Aripiprazole - (Abilify)

Clozapine - (Clozaril) - if resistant

First 4 are all first line and are chosen depending on side effect profile and preparation

Question 13

What is Risperidone?

What side effects can it cause?

Answer 13

Atypical antipsychotic - although functions more like a typical antipsychotic at higher doses

Side effects:

• extrapyramidal - dose dependant
• hyperprolactinaemia - sexual dysfunction etc
• weight gain & sedation

Question 14

What is Olanzapine?

What side effects can it cause?

Answer 14

Atypical antipsychotic

May cause:

• severe weight gain
• hypertryglyceridaemia, hypercholesterolaemia, hyperglycaemia
• hyperprolactinaemia
• abnormal LFTs

Question 15

What is Quetiapine?

Side effects?

Answer 15

Atypical antipsychotic

May cause:

• orthostatic hypotension
• abnormal LFTs
• weight gain
• hyper: triglycerides, cholesterol, glycaemia

Question 16

What is Aripiprazole (Abilify)?

What are its benefits?

Side effects?

Answer 16

Atypical antipsychotic - unique mechanism as a partial D2 agonist

This means its less associated with extrapyramidal side effects, no QT prolongation, no sedation, no weight gain

Side effects:

• akathisia/activation
• interactions with fluoxetine, paroxetine

Question 17

What antipsychotics are useful for immediate sedation?

Why is this?

ie in an emergency situation with a psychotic patient

Answer 17

Olanzapine (Zyprexa)

Aripiprazole (Abilify)

Available in immediate release IM form

Question 18

What is clozapine?

Answer 18

Clozapine (Clozaril)

Tablet only Antipsychotic used for treatment resistant psychosis (ie if first lines do not work)

Very effective but with quite bad potential side effects

Question 19

What are the side effects of clozapine?

Answer 19

Agranulocytosis:

• patients on clozapine require weekly bloods for 6 months, then fortnightly bloods for 6 months

Increased risk of seizures (esp if on lithium)

Most sedation, weight gain and abnormal LFTs

Hyper: triglycerides, cholesterol, glycaemia & risk of hyperosmolar coma and death

Question 20

What specific groups of adverse affects can be caused by any of these antipsychotics (typical and atypical)?

Already mentioned a lot but for some reason this has its own slide so must be important

Answer 20

Tardive dyskinesia (esp w/ typical antipsychotics)

involuntary muscle movements

Neuroleptic malignant syndrome (NMS)

characterized by severe muscle rigidity, fever, altered mental status, autonomic instability, elevated WBC, CPK and lfts

Extrapyramidal side effects (EPS)

acute dystonia, Parkinson syndrome, Akathisia

Question 21

What agents are available to treat EPS?

Answer 21

Anticholinergics such as benztropine, trihexyphenidyl, diphenhydramine

Dopamine facilitators such as Amantadine

Beta-blockers such as propranolol

Watch for anticolinergic side effects