Pharmacological Treatment of Schizophrenia Flashcards Preview

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Flashcards in Pharmacological Treatment of Schizophrenia Deck (35)
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What are the goals of treatment in acute schizophrenia?

Reduce behavioural disturbance and positive symptoms (hallucinations and delusions)


What are the goals of maintenance treatment in schizophrenia?

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


What is chlorpromazine?

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


What is haloperidol?

A first-generation antipsychotic and D2 receptor blocker


Name the only drug licensed for treatment resistant schizophrenia



What is the most serious side effect of clozapine?



Name at least 5 second-generation antipsychotics

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


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



Why can antipsychotics cause osteoporosis and sexual side effects?

They tend to increase prolactin


Name the 4 main dopamine pathways in the brain

Nigrostriatal, mesolimbic, mesocortical, tuberoinfundibular


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


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


Describe the mesocortical pathway

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


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


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


Describe evidence of dopaminergic system abnormalities in schizophrenia from SPECT imaging

Amphetamine-induced dopamine release is higher in schizophrenics than controls


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


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

The clinical efficacy correlates with their affinity for the D2 receptor


What is the threshold for antipsychotic efficacy?

Above 65% D2 receptor occupancy


What is the threshold for extrapyramidal side effects?

Above 80% D2 receptor occupancy


What is the most significant side effect of antipsychotics?

Weight gain


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



Describe the hypothesis of supersensitivity psychosis

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


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

1 in 6


State some potential consequences of relapse

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


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


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



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


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


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