Schizophrenia

• what are the positive and negative symptoms associated with schizophrenia?

  positive = delusions - unshakeable false belief, hallucinations - presents usually as running commentary or on command for auditory, disordered thinking - thought interference

  negative = social withdrawal, cognitive deficits, avolition, drug and alcohol abuse, mood alterations usually depression
• what are the roles of dopamine pathways in schizophrenia?

  mesolimbic pathway - excess dopamine activity = positive symptoms such as hallucinations and delusions

  mesocortical pathway - diminished dopamine activity - negative symptoms such as emotions thought speech, pleasure and attention
• what is the role of glutamate in schizophrenia?

  linked with dopamine - NMDA antagonists can cause psychosis, alterations in glutamate and its receptors seen in schizophrenia
• what is the role of GABA in schizophrenia?

  decrease in synthetic enzyme activity - GABAergic neurone density reduced and expression of GABA receptors altered in schizophrenia
• what are the pharmacological options for treatment?

  long term treatment with antipsychotics - first episode more sensitive, compliance is important, treatment resistance develops over time
• how long is treatment usually given for?

  generally life long - associated with physical illness, self harm, suicide and victimisation - life expectancy reduced by 10 years

  made worse by early onset, poor premorbid function, poor insight and social isolation associated with treatment
• how do typical antipsychotics work?

  also known as first generation

  D2 receptor antagonists - older and more side effects, hyperprolactinemia and prolonged QTc

  potent D2R antagonists - benperidol, haloperidol, piotiazine, pimozide

  moderately potent D2 antagonists - chlorpromazine, perphenazine and trifluoperazine
• what are EPSEs?

  movement disorders - caused by disruption in dopaminergic transmission and correlated with D2 receptor occupancy

  ADAPT - acute dystonia, akathisia, pseudo-parkinsonism, tardive dyskinesia
• how are the different EPSEs treated?

  acute dystonia - involuntary muscle contraction - treat with anti-ACh (procyclidine)

  akathisia - rocking from foot to foot linked to suicide - treat with beta blockers, 5-HT2 antagonists or BZDs - procyclidine

  pseudoparkinsonism - procyclidine, reduce dose of FGA and tremor

  tardive dyskinesia - involuntary muscle movements - switch antipsychotic, treat with gradual dose reduction, stop or reduce anticholinergic
• how do atypical antipsychotics work?

  reduced incidence of EPSEs - possibly due to more 5-HT receptor antagonism

  risperidone and olanzapine can cause them at higher doses

  include amisulpride, aripiprazole, olanzapine, risperidone and quetiapine

  olanzapine has tobacco smoking interactions

  risperidone - high affinity for 5-HT2 receptors

  quetiapine - antagonism of D2 and 5-HT receptors

  aripiprazole - partial agonist at D2 receptors

  amisulpride - dopamine receptor antagonist that selectively works on D2 and D£ receptors
• how does clozapine work and when is it prescribed?

  low affinity for D2 receptors, high affinity for D4 and 5-HT receptors

  2 failed treatments - 1 of which is SGA before clozapine prescribed
• what are the cautions for clozapine?

  need FBCs - risk of agranulocytosis, WBC, NC, platelets and eosinophils recorded, weekly FBC for 18 weeks, every 2 weeks for remainder of 1st year and then monthly
• what is the traffic light system for clozapine monitoring?

  green if WBC more than 3.5 and NC more than 2

  red if WBC less than 3 and NC less than 1.5

  amber if in between - in this case should monitor 2 more times per week
• what are food and drink interactions with clozapine?

  infections can send you toxic

  look after your heart

  constipation is dangerous and can send you toxic

  caffeine and alcohol in moderation

  change in smoking can send you toxic
• what is the tobacco smoke interaction with clozapine?

  hydrocarbons in tobacco induce CYP1A2

  responsible for olanzapine and clozapine metabolism

  reduced plasma levels of olanzapine and clozapine by 25%

  reduce dose by 25% if baseline high and side effects are apparent

  think about this in contect of hospital where smoking is prohibited
• what is NMS?

  rare but potentially fatal side effect of all antipsychotics

  hyperthermia

  fluctuating levels of consciousness

  muscle rigidity

  autonomic dysfunction - pallor tachycardia, labile BP

  sweating

  urinary incontinence

  associated with changes in dose or formulation or imitating new medicine