Schizophrenia: Pharmacological treatments Flashcards
What are some first generation antipsychotics and how to they act?
Chlorpromazine- loads of actions (antihistamine, anticholinergic, D2 blocker)
Haloperidol- Selective D2 blocker, without side effects.
What is the best SGA and what are some side effects?
Clozapine- people resistant to FGA responded to this. It has a large number of actions- acts more on the serotonin receptor, no effect on D2.
Side effects:
Agranulocytosis, Cardiovascualr problems.
What is the dopamine theory of schizophrenia?
Drugs such as amphetamine and cocaine release DA cause psychosis. There is worsening of psychotic symptoms in patients. This suggests DA is overactive in schizophrenia.
Imaging suggests there is heightened DA synthesis, and positive symptoms due to excess DA function.
What is the % occupancy threshold for antipsychotic efficacy?
65% D2 receptor occupancy.
> 78% occupancy for EPS, including akathisia. Applies both to FGAs and SGAs.
What is motivational salience and why is this important in psychosis?
This is us being able to respond to stimuli in a goal driven way as there is a reward associated grabbing of attention.
Environmental / Genetic predisposition-> Dysregulated firing of Dopamine-> Aberrant “Motivational Salience” -> Brain told motivation salience (something important), Changes focus BUT no obvious stimuli
->Cognitive schema to explain aberrant experience->Delusional mood->Pick up more evidence to re-inforce delusion
What was the CAFE study?
Compared SGAs in FEP. (Olanzapine, quetiapine, risperidone).
There was no large difference in discontinuation.
Young people with early psychosis: Increased sensitivity to substantial weight gain
What is the difference in perception of side effects of FGAs and SGAs?
FGAs: Movement and endocrine effects
SGAs: Metabolic and cardiovascular complications.
What is the relapse rate difference between withdrawal and maintenance groups of medication?
Withdrawal: 53%
Maintenance: 16%
What is the difference between abrupt and gradual discontinuation?
Gradual: Halved 6 month relapse rate
Abrupt: 46% relapse rate.
What is the hypothesis of supersensitivity psychosis?
Antipsychotic induced upregulation of D2 receptors.
This is potentially responsible for rebound psychosis, breakthrough of psychotic symptoms, medication tolerance.
What are the consequences of relapse?
Prolonged periods are associated with poor prognosis, social function, worsening of symptoms, reduced quality of life.
Is psychosis neurotoxic?
What are the advantages of DEPOT/long acting injectables?
Advantages: Avoid covert non-adherence- regular delivery of known dose.
Regular scrutiny of mental state and side effects
Simplification of medication regimen
Cons: Slow dose titration, longer time required to achieve steady state.
Increase risk of excess dosage
Pain/discomfort at injection site.
Why should DUP be avoided?
Neuropsychoses potentially neurotoxic. Causes a worse outcome.
What did the Hunt Paper find?
Substance abuse wipes out any benefit of antipsychotic medications.
