Treatment of Psychosis and Psychotic Disorders Flashcards
How many dopaminergic pathways are in the brain?
4
What are the four dopaminergic pathways?
Mesolimbic
Mesocortical
Nigrostriatal
Tuberoinfundibular
What is the mesolimbic system regulate?
The limbic system
What is the mesolimbic system responsible for?
Reward processing (pleasure)
Salience (threat evaluation)
Where does the mesolimbic pathway run?
From the ventral segmental area to the nucleus accumbens & striatum (midbrain)
What is salience?
The brain’s ability to attune to relevant stimuli and block our irrelevant stimuli
How does psychosis arise from the mesolimbic pathway?
Mesolimibic pathway becomes hyperactive - dysfunction means that the brain’s salience mechanism becomes dysfunctional.
How do drugs of abuse affect the mesolimbic pathway?
They target the reward processing part = pleasure feelings.
What can chronic drug use cause?
Dysregulation of the salience part of the mesolimbic pathway = drug-induced psychosis
Where does the mesocortical pathway run?
From the ventral tegmental area to the prefrontal cortex
What is the mesocortical pathway responsible for?
Cognition
Motivation
Social Engagement
How does psychosis affect the mesocortical system?
Makes it hypoactive = reduced stimulation to the prefrontal cortex = negative psychosis symptoms (cognitive impairment & social withdrawal)
What does the nigrostriatial system do?
Regulates basal ganglia (involved in initiation of movement)
How do antipsychotics affect the nigrostriatal system?
Cause impaired movement by interfering with the nigrostriatal pathway.
What does the tuberoinfinduibular system regulate?
The HPA axis - therefore control of endocrine system
How do antipsychotics affect the tuberoinfundibulnar system?
They can interfere in this pathway - causing hormonal problems in Ps.
What type of drug are antipsychotics?
They are postsynaptic dopamine antagonists
What percentage of dopamine should antipsychotics block?
60-70%
How do antipsychotics affect the mesolimbic system?
They suppress both pleasure & threat evaluation.
Cause dysphoria (loss of pleasure in life)
What often leads Ps to abandon their antipsychotic medication?
Dysphoria (loss of pleasure in life)
How do antipsychotics traditionally affect the mesocortical system?
Depress it further - worsening negative symptoms
How do traditional antipsychotics affect psychosis?
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)
What is the difference between first and second generation antipsychotics?
First generation = were big dopamine blockers = lots of side effects (e.g. Parkinsons)
Second Generation = target other NTs such as serotonergic pathways
What do first generation antipsychotics cause by inhibiting the nigrostriatal and tuberoinfundibulnar pathways?
Movement and hormone dysfunctions
What side effects were reduced by second generation antipsychotics?
However - what side effects were reported instead?
Movement and hormonal side effects were reduced.
BUT
cardia-metabolic symptoms were reported instead (diabetes, weight gain & CVS disease)
What are the differences between how first and second generation antipsychotics work?
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
Which second generation antipsychotic is the most effective?
Clozapine
When do you use Clozapine?
Treatment-resistance illness
Therefore - when you’ve tried at least two other antipsychotics before being prescribed this
What is the most important factor in determining recovery from psychosis?
Duration of untreated psychosis - the longer this psychosis persists untreated, the worse the outcomes are.
Why do psychiatrists not prescribe clozapine earlier?
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.
Why should we use long-term antipsychotics?
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.
What is the downside to long-term use of antipsychotics?
If dopamine receptors are continually blocked, sometimes cells respond by increasing the number of receptors
When the nigrostriatal pathway is blocked - what type of side effects does it cause?
Extrapyramidal side effects
What symptoms are included in extrapyramimdal side effects?
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)
In what 3 ways do antipsychotics produce cardio metabolic side effects?
Affect hypothalamus = no satiety - Ps commonly overeat
Raise serum lipid & cholesterol levels
Affect glucose tolerance & impact on insulin = inc levels of T2 diabetes
How do antipsychotics affect the heart? What should you do before and during their use?
Affects the QT interval of the heart
MUST give ECG before prescribing and monitor with ECGs
On average how much earlier do Ps die when they have psychosis?
What do they usually die from?
15-20 years earlier
Usually from cardiovascular disease (but not necessarily because of antipsychotics side effects)
Why is cardiovascular disease a common cause of death for Ps with mortality?
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
Does the amount of medication that you are on impact your mortality rates?
Why?
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
Name three alternative treatments to antipsychotic meds for mental illness.
CBT (Cognitive Behavioural Therapy)
Arts Therapy
Family intervention
