Schizophrenia - Treatment 2 (drugs)

Question 1

What are the typical antipsychotics? What are they classed on?

Answer 1

phenothiazines

• chlorpromazine
• thioridazine (high anti-muscarinic potential)

haloperidol
flupentixol
sulpiride
fluphenazine

Question 2

How do the typical antipsychotics work? What are their benefits and side effects?

Answer 2

chlorpromazine
- has anti-muscarinic properties therefore less extrapyramidal effects, very sedative (D2/H1)
thioridazine
- has anti-muscarinic properties and is rarely associated with movement disorders, cause sexual dysfunction, not sedative (no H1)

haloperidol
- no anti-muscarinic properties, has high incidence of motor disorders
flupentixol
fluphenazine (depot)
sulpiride
- selective D2 antagonism to the mesolimbic pathway, fewer motor effects, little sedation

Question 3

What are the atypical antipsychotics?

Answer 3

clozapine
olanzapine
risperidone
aripiprazole

Question 4

How do the atypical antipsychotics work? What are their benefits and side effects?

Answer 4

clozapine

• no EPSe as its highly specific for D2 receptors in the mesolimbic pathway and has fast dissociation
• high D4 blocking activity
• side effects: weight gain, neutropenia, agranulocytosis

olanzapine

risperidone

• no anti-muscarinic properties (no M1 binding), no EPSE at lower doses but is seen at higher doses
• 5-HT2 antagonism and D2 antagonism (stronger than clozapine)

aripiprazole

Question 5

What are the common side effects of typical antipsychotics?

Answer 5

movement disorders/extrapyramidal side effects (EPSE)

• parkinsonian = tremor, slow movement, muscle stiffness
• dystonia = muscles contract involuntarily, causing repetitive or twisting movements
• tardive dyskinesia = sudden, irregular facial and body movements (develops after chronic use and is irreversible)

breast swelling (gynaecomastia)
lactation 

decreased pleasure
- apathy

sedation
- inhibition of aggression (D2/H1)
weight gain
photosensitisation

Question 6

What are the common side effects of atypical antipsychotics?

Answer 6

fewer EPSE and movement disorders
increased QT interval (ziprasidone)
increased risk of myocardial infarction/stroke

Question 7

What problems do patients have with antipsychotics? How can these be solved?

Answer 7

mainly effective against positive symptoms but is limited for negative symptoms
limited improvement for most patients
no improvement for some patients even with prolonged therapy
relapse common in drug-maintained patients
compliance

compliance
- longer acting antipsychotics means they can be taken less frequently (orally or i.m.)
- can be taken as depot injections
= i.m injections of oily suspensions increase duration of effectiveness and compliance
e.g. fluphenazine

Question 8

What are the options for future drug development?

Answer 8

drugs which increase glutamate, NMDA and AMPA activity
- glutamate theory suggests that low Glu in the frontal cortex is associated with negative symptoms

agonists of metabotropic glutamate receptors

drugs which dissociate from D2 receptors quickly

drugs which

• decrease D2 activity in the mesolimbic
• have no D2 effect in the nigrostriatal
• increase D2 effect in the mesocorticol