Treatment of Psychosis and Psychotic Disorders

Question 1

How many dopaminergic pathways are in the brain?

Answer 1

4

Question 2

What are the four dopaminergic pathways?

Answer 2

Mesolimbic

Mesocortical

Nigrostriatal

Tuberoinfundibular

Question 3

What is the mesolimbic system regulate?

Answer 3

The limbic system

Question 4

What is the mesolimbic system responsible for?

Answer 4

Reward processing (pleasure)

Salience (threat evaluation)

Question 5

Where does the mesolimbic pathway run?

Answer 5

From the ventral segmental area to the nucleus accumbens & striatum (midbrain)

Question 6

What is salience?

Answer 6

The brain’s ability to attune to relevant stimuli and block our irrelevant stimuli

Question 7

How does psychosis arise from the mesolimbic pathway?

Answer 7

Mesolimibic pathway becomes hyperactive - dysfunction means that the brain’s salience mechanism becomes dysfunctional.

Question 8

How do drugs of abuse affect the mesolimbic pathway?

Answer 8

They target the reward processing part = pleasure feelings.

Question 9

What can chronic drug use cause?

Answer 9

Dysregulation of the salience part of the mesolimbic pathway = drug-induced psychosis

Question 10

Where does the mesocortical pathway run?

Answer 10

From the ventral tegmental area to the prefrontal cortex

Question 11

What is the mesocortical pathway responsible for?

Answer 11

Cognition
Motivation
Social Engagement

Question 12

How does psychosis affect the mesocortical system?

Answer 12

Makes it hypoactive = reduced stimulation to the prefrontal cortex = negative psychosis symptoms (cognitive impairment & social withdrawal)

Question 13

What does the nigrostriatial system do?

Answer 13

Regulates basal ganglia (involved in initiation of movement)

Question 14

How do antipsychotics affect the nigrostriatal system?

Answer 14

Cause impaired movement by interfering with the nigrostriatal pathway.

Question 15

What does the tuberoinfinduibular system regulate?

Answer 15

The HPA axis - therefore control of endocrine system

Question 16

How do antipsychotics affect the tuberoinfundibulnar system?

Answer 16

They can interfere in this pathway - causing hormonal problems in Ps.

Question 17

What type of drug are antipsychotics?

Answer 17

They are postsynaptic dopamine antagonists

Question 18

What percentage of dopamine should antipsychotics block?

Answer 18

60-70%

Question 19

How do antipsychotics affect the mesolimbic system?

Answer 19

They suppress both pleasure & threat evaluation.

Cause dysphoria (loss of pleasure in life)

Question 20

What often leads Ps to abandon their antipsychotic medication?

Answer 20

Dysphoria (loss of pleasure in life)

Question 21

How do antipsychotics traditionally affect the mesocortical system?

Answer 21

Depress it further - worsening negative symptoms

Question 22

How do traditional antipsychotics affect psychosis?

Answer 22

They suppress dopamine - so they can lessen some of the positive symptoms (via suppression of mesolimbic system) but they can exacerbate the negative symptoms (via the mesocortical system)

Question 23

What is the difference between first and second generation antipsychotics?

Answer 23

First generation = were big dopamine blockers = lots of side effects (e.g. Parkinsons)

Second Generation = target other NTs such as serotonergic pathways

Question 24

What do first generation antipsychotics cause by inhibiting the nigrostriatal and tuberoinfundibulnar pathways?

Answer 24

Movement and hormone dysfunctions

Question 25

What side effects were reduced by second generation antipsychotics? However - what side effects were reported instead?

Answer 25

Movement and hormonal side effects were reduced. BUT cardia-metabolic symptoms were reported instead (diabetes, weight gain & CVS disease)

Question 26

What are the differences between how first and second generation antipsychotics work?

Answer 26

First generation = dopamine antagonist - binds to the postsynaptic receptor and blocks 60-70 of dopaminergic receptors. Second generation = still block 60-70% of dopaminergic receptors BUT have more dynamic "off-time" = reduced side effects. ALSO - bind to 5HT2A receptor on presynaptic neuron = slows down the release of dopamine into the cleft

Question 27

Which second generation antipsychotic is the most effective?

Answer 27

Clozapine

Question 28

When do you use Clozapine?

Answer 28

Treatment-resistance illness Therefore - when you've tried at least two other antipsychotics before being prescribed this

Question 29

What is the most important factor in determining recovery from psychosis?

Answer 29

Duration of untreated psychosis - the longer this psychosis persists untreated, the worse the outcomes are.

Question 30

Why do psychiatrists not prescribe clozapine earlier?

Answer 30

Because of its serious side effects Apart from weight gain, CVS & diabetes problems - it can also cause neutropenia (low WBCs) & low granulocytes. Can be very problematic for Ps.

Question 31

Why should we use long-term antipsychotics?

Answer 31

Effectiveness in treating positive symptoms is proven & maintenance of P mental health is well established. No good evidence that there is long-term harm from them - is no good evidence that there are brain changes from antipsychotic usage.

Question 32

What is the downside to long-term use of antipsychotics?

Answer 32

If dopamine receptors are continually blocked, sometimes cells respond by increasing the number of receptors

Question 33

When the nigrostriatal pathway is blocked - what type of side effects does it cause?

Answer 33

Extrapyramidal side effects

Question 34

What symptoms are included in extrapyramimdal side effects?

Answer 34

Acute dystonia (sharp muscle spasms in face and neck) Akathisia (inner restlessness) Parkinsonism (stiffness of movement) Tardive dyskinesia (long-term abnormal movements of moths and lips)

Question 35

In what 3 ways do antipsychotics produce cardio metabolic side effects?

Answer 35

Affect hypothalamus = no satiety - Ps commonly overeat Raise serum lipid & cholesterol levels Affect glucose tolerance & impact on insulin = inc levels of T2 diabetes

Question 36

How do antipsychotics affect the heart? What should you do before and during their use?

Answer 36

Affects the QT interval of the heart MUST give ECG before prescribing and monitor with ECGs

Question 37

On average how much earlier do Ps die when they have psychosis? What do they usually die from?

Answer 37

15-20 years earlier Usually from cardiovascular disease (but not necessarily because of antipsychotics side effects)

Question 38

Why is cardiovascular disease a common cause of death for Ps with mortality?

Answer 38

Because Ps dont look after themselves Social factors can play a part Side effects are not managed as well as they could be by doctors

Question 39

Does the amount of medication that you are on impact your mortality rates? Why?

Answer 39

Compared to zero medication - you have lower mortality rates if you take moderate or high antipsychotics. Although medication does have side effects (which can be harmful) - on the balance with improved mental health, Ps are more likely to visit GP, take other medications, engage in exercise and be happier and healthier

Question 40

Name three alternative treatments to antipsychotic meds for mental illness.

Answer 40

CBT (Cognitive Behavioural Therapy) Arts Therapy Family intervention