17: Antipsychotics

Question 1

What criteria must be met to be diagnosed with schizophrenia?

Answer 1

Must last 6+ months, including at least 1 month of delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behaviour, or negative sx.

Question 2

Introduction of _____ in _____ reduced number of patients in psychiatric hospitals worldwide.

Answer 2

Chlorpromazine; 1955.

Question 3

What percentage of the population suffers from schizophrenia? What percentage accounts for all healthcare costs?

Answer 3

1-1.5% of the population. Accounts for 2.5% of all healthcare costs.

Question 4

What is the sex ratio of schizophrenia?

Answer 4

1.2:1, males affected slightly more often than females.

Question 5

Describe the common social functioning of an individual with schizophrenia.

Answer 5

Very few friends/social contacts. 60-70% do not marry or have children.

Question 6

What is the suicide risk for an individual with schizophrenia?

Answer 6

25-50% attempt suicide, 20x higher risk than general population.

Question 7

What is a common stigma pertaining to schizophrenia?

Answer 7

70% of those questioned in a survey believed schizophrenics were dangerous and unpredictable.

Question 8

What are the five symptom dimensions of schizophrenia?

Answer 8

Positive symptoms.
Negative symptoms.
Aggressive symptoms.
Cognitive symptoms.
Anxiety/depression.

Question 9

What is the dopamine hypothesis pertaining to schizophrenia? List two pieces of evidence.

Answer 9

Schizophrenia due to excessive mesolimbic DA signaling.

Evidence: dopaminergic drugs induce psychotic-like sx; dopamine blockers alleviate sx, likely due to D2-like receptors.

Question 10

Aside from dopamine, what two other neurotransmitter systems are targeted by antipsychotics?

Answer 10

Serotonin: 5-HT2A receptor.

Glutamate: 5-HT2 activation → enhance cortical glutamate neurons.

Question 11

What are other terms for first-generation antipsychotics?

Answer 11

Neuroleptics, major tranquilizers, conventional or typical antipsychotics.

Question 12

Second-generation antipsychotics (atypical) share what in common with first-generation? Why might atypicals be better?

Answer 12

Both groups block D2 and 5-HT2 receptors. Atypicals are more potent at the 5-HT receptors (better side effect profile).

Question 13

What is the function of typical antipsychotics? What are the side effects?

Answer 13

Antagonize D2r eceptors, weaker antagonists at 5-HT2 receptors.

Side effects: motor (extrapyramidal).

Question 14

What is the function of atypical antipsychotics? What are the side effects?

Answer 14

Antagonize 5-HT2 receptors, antagonize D3/4 receptors, weaker at D2 receptors. Treats negative sx.

Side effects: fewer motor than typical.

Question 15

What are the three commonly used tests/models for testing antipsychotics?

Answer 15

Prepulse inhibition (PPI): loud noise preceded by warning noise. Schizophrenics do not show any PPI.

Early hippocampal lesions: reduces PPI in rodents.

Isolation rearing: shows behavioural and neurochemical similarities with human patients.

Question 16

List five questionnaires/rating scales for schizophrenia. List one for measuring side effects of antipsychotics.

Answer 16

Schizophrenia:

Brief Psychiatric Rating Scale
Positive and Negative Syndrome Scale
Quality of Life Scale
Clinical Global Impression Scale
Global Outcome Assessment of Life in Schizophrenia (GOALS)

Side effects:

Extrapyramidal Symptom Rating Scale

Question 17

PANNS studies measuring typical (haloperidol) vs. atypical (olanzapine) drugs found what? What was found in a PPI study?

Answer 17

Olanzapine resulted in significant effect on negative symptoms in week 12. No effect on positive symptoms. Significant effect for olanzapine from week 2.

PPI study: risperidone resulted in significant decrease from baseline, haloperidol greater effect than olanzapine.

Question 18

Why do extrapyramidal sx occur? List three of the sx.

Answer 18

Due to effects on D2a ntagonism in nigrostriatal system.

Dyskinesias (movement disorders); Akathisia (extreme restlessness); Dystonias (muscle tension disorders).

Question 19

Why do atypical antipsychotics have a lower risk of extrapyramidal sx? List two risks atypicals have.

Answer 19

Lower risk because D3/4affinity > D2, and 5-HT2A antagonism cancels out D2 effects.

Risk of agranulocytosis (bone marrow), potentially fatal.
Metabolic effects - more weight gain vs. typical antipsychotic.

Question 20

What effect does olanzapine have on cocaine conditioned place preference?

Answer 20

Reduces cocaine CPP.

Question 21

What poses a treatment problem for schizophrenia and why?

Answer 21

Anosognosia - lack of awareness of the nature of one’s illness. Factor in nonadherence to treatment regimens and increased risk of relapse.

Question 22

What are the neurodevelopmental and neurogenerative hypotheses pertaining to schizophrenia?

Answer 22

Decline in four stages. Theorized apoptosis/necrosis occurs in Stage III.

Question 23

What are three arguments for an autoimmune origin pertaining to schizophrenia?

Answer 23

Schizophrenia runs in families but an identical twin has only 50% chance to develop schizophrenia.

Rheumatoid arthritis/schizophrenia discordance.

3 immune response gene regions were associated with genes predisposing to schizophrenia.