Pharmacological Treatment of Schizophrenia Flashcards Preview

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Flashcards in Pharmacological Treatment of Schizophrenia Deck (35)
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1

What are the goals of treatment in acute schizophrenia?

Reduce behavioural disturbance and positive symptoms (hallucinations and delusions)

2

What are the goals of maintenance treatment in schizophrenia?

Prevent relapse, improve negative symptoms, reduce cognitive deficits, aid psychosocial reintegration, encourage adherence

3

What is chlorpromazine?

A broad-spectrum first-generation antipsychotic which acts as an anti-dopaminergic, anti-cholinergic, and anti-histaminergic

4

What is haloperidol?

A first-generation antipsychotic and D2 receptor blocker

5

Name the only drug licensed for treatment resistant schizophrenia

Clozapine

6

What is the most serious side effect of clozapine?

Agranulocytosis

7

Name at least 5 second-generation antipsychotics

Risperidone, olanzapine, quetiapine, zotepine, aripiprazole, brexipirazole, sertindole, amisulpride, asenapine, lurasidone

8

What percentage of individuals respond to second-generation antipsychotics? (Leucht et al, 2012)

41%

9

Why can antipsychotics cause osteoporosis and sexual side effects?

They tend to increase prolactin

10

Name the 4 main dopamine pathways in the brain

Nigrostriatal, mesolimbic, mesocortical, tuberoinfundibular

11

Describe the nigrostriatal pathway

A dopaminergic pathway running from the substantia nigra to the caudate and putamen (striatum), associated with the initiation of motor plans

12

Describe the mesolimbic pathway

A dopaminergic pathway running from the ventral tegmental area in the midbrain to the limbic region (nucleus accumens, amygdala, hippocampus, medial prefrontal cortex). It is associated with reward, motivation, affect, and memory

13

Describe the mesocortical pathway

A dopaminergic pathway running from the ventral tegmental area to the frontal cortex and associated with reward and motivation

14

Describe the tuberoinfundibular pathway

A dopaminergic pathway running from the tuberal region to the median eminence (inferofundibular region at the top of the pituitary stalk). It is associated with prolactin release

15

Give some evidence for the dopamine theory of schizophrenia

1) Psychostimulant agents that trigger dopamine release are associated with de novo psychosis and worsening of psychosis in patients in remission
2) PD patients given L-DOPA can develop hallucinations

16

Describe evidence of dopaminergic system abnormalities in schizophrenia from SPECT imaging

Amphetamine-induced dopamine release is higher in schizophrenics than controls

17

Describe the difference in positive and cognitive symptom pathogenesis in schizophrenia (Silfstein et al, 2015)

Positive symptoms are believed to be due to excess dopamine function in the striatum, whereas cognitive symptoms are believed to be due to insufficient dopamine function in the prefrontal cortex

18

How does the clinical efficacy of antipsychotics support the dopamine hypothesis of schizophrenia?

The clinical efficacy correlates with their affinity for the D2 receptor

19

What is the threshold for antipsychotic efficacy?

Above 65% D2 receptor occupancy

20

What is the threshold for extrapyramidal side effects?

Above 80% D2 receptor occupancy

21

What is the most significant side effect of antipsychotics?

Weight gain

22

How much is the relapse risk increased by discontinuing antipsychotics compared to maintenance therapy? (Viguera et al, 1997)

5x

23

Describe the hypothesis of supersensitivity psychosis

It theorises that antipsychotic medication causes a compensatory state of upregulation of D2 receptors

24

In what proportion of schizophrenia patients does treatment refractoriness emerge after relapse? (Ohmori et al, 1999)

1 in 6

25

State some potential consequences of relapse

Risk of harm to self or others, disruption of personal relationships, education, and employment status

26

Describe the consequences of long-term antipsychotic use

Changes in brain structure (parietal lobe and basal ganglia), metabolic side effects, direct cardiotoxic effects, increased risk of CHD, CVD, and CHF

27

What percentage of patients are estimated to be poorly or non-adherent? (Kane et al, 2013)

50-75%

28

Describe the effect of comorbid substance abuse on relapse (Hunt et al, 2002)

It increases the risk of relapse, with a greater negative effect in those who are medication adherent than those who are non-adherent

29

Kirson et al's 2013 meta-analysis found no advantage in using long-acting formulations over oral antipsychotics in RCTs. Give some potential reasons why

1) Only selecting adherent patients, removing the advantage of adherence
2) Increased monitoring for both groups
3) Too short-term to see the long-term benefts

30

State some advantages of long-acting antipsychotics

Avoid covet non-adherence, regular delivery of a known dose, regular scrutiny of mental state and side effects, simplification of medication regime, more predictable and stable serum drug level