Pharmacological Treatment of Schizophrenia

Question 1

What are the goals of treatment in acute schizophrenia?

Answer 1

Reduce behavioural disturbance and positive symptoms (hallucinations and delusions)

Question 2

What are the goals of maintenance treatment in schizophrenia?

Answer 2

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

Question 3

What is chlorpromazine?

Answer 3

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

Question 4

What is haloperidol?

Answer 4

A first-generation antipsychotic and D2 receptor blocker

Question 5

Name the only drug licensed for treatment resistant schizophrenia

Answer 5

Clozapine

Question 6

What is the most serious side effect of clozapine?

Answer 6

Agranulocytosis

Question 7

Name at least 5 second-generation antipsychotics

Answer 7

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

Question 8

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

Answer 8

41%

Question 9

Why can antipsychotics cause osteoporosis and sexual side effects?

Answer 9

They tend to increase prolactin

Question 10

Name the 4 main dopamine pathways in the brain

Answer 10

Nigrostriatal, mesolimbic, mesocortical, tuberoinfundibular

Question 11

Describe the nigrostriatal pathway

Answer 11

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

Question 12

Describe the mesolimbic pathway

Answer 12

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

Question 13

Describe the mesocortical pathway

Answer 13

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

Question 14

Describe the tuberoinfundibular pathway

Answer 14

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

Question 15

Give some evidence for the dopamine theory of schizophrenia

Answer 15

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

Question 16

Describe evidence of dopaminergic system abnormalities in schizophrenia from SPECT imaging

Answer 16

Amphetamine-induced dopamine release is higher in schizophrenics than controls

Question 17

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

Answer 17

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

Question 18

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

Answer 18

The clinical efficacy correlates with their affinity for the D2 receptor

Question 19

What is the threshold for antipsychotic efficacy?

Answer 19

Above 65% D2 receptor occupancy

Question 20

What is the threshold for extrapyramidal side effects?

Answer 20

Above 80% D2 receptor occupancy

Question 21

What is the most significant side effect of antipsychotics?

Answer 21

Weight gain

Question 22

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

Answer 22

5x

Question 23

Describe the hypothesis of supersensitivity psychosis

Answer 23

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

Question 24

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

Answer 24

1 in 6

Question 25

State some potential consequences of relapse

Answer 25

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

Question 26

Describe the consequences of long-term antipsychotic use

Answer 26

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

Question 27

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

Answer 27

50-75%

Question 28

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

Answer 28

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

Question 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

Answer 29

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

Question 30

State some advantages of long-acting antipsychotics

Answer 30

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

Question 31

State some disadvantages of long-acting antipsychotics

Answer 31

Slow dose titration with a long time needed to achieve a steady state, increased risk of excess dosage, pain and discomfort at injection site

Question 32

At what point is clozapine trialled?

Answer 32

After no adequate response to 2 trials of antipsychotic medication, confirmation of adequate dosage and correct diagnosis, and trialling high-dose antipsychotic medication

Question 33

State some clinician-related barriers to initiating clozapine treatment

Answer 33

Need for intense monitoring, risk of serious side effects, lack of adherence by patient

Question 34

State some system-related barriers to initiating clozapine treatment (Farooq et al, 2018)

Answer 34

Difficulty in identifying suitable patients, service fragmentation, inadequate training in or exposure to use of clozapine

Question 35

How often must patients on clozapine undergo haematological monitoring in the first 18 weeks?

Answer 35

Weekly