Schizophrenia Flashcards
psychosis/psychotic episode
- acute and severe ep of mental condition
- out of touch with reality (disordered thought process, beliefs, perceptions)
- lack of insight
Definition of Schizophrenia
- common form of protracted psychosis for > 6 months
- heterogenous syndrome of disorganised and bizarre thoughts, delusions, hallucinations, impaired psychosocial functioning
primary pathophysiology of Schizophrenia
- abnormality in neurotransmitters (dopaminergic (DA), serotonergic (5-HT)
predisposing factors for Schizophrenia
1) genetics
- chromosomes 6, 8, 13, 15, 22
2) environmental in utero
3) neurodevelopmental effect
4) personality
5) physical, psychological and social factors in infancy and early childhood
precipitating factors for Schizophrenia
1) Cerebral tumour/injury
2) drug/substance induced psychosis
- need to rule out immediately
- alcohol, benzodiazepine, barbiturate, antidepressant, corticosteroids, CNS stimulants (amphetamine), hallucinogens, beta blockers, dopamine agonist (levodopa)
3) personal misfortune
4) environment of high expressed emotion
perpetuating factors for Schizophrenia
1) Secondary demoralisation
2) social withdrawal
3) lack of support/poor socioeconomic status/environment
4) poor adherence to meds
- more relapse = more resistant development = harder to treat
DSM-5 criteria for Schizophrenia
1) 2 or more of following for at least 1 month period
- delusion
- hallucination
- disorganised speech
- grossly disorganised or catatonic behaviour (not aware of surrounding)
- negative symptoms
** affective flattening: feel emotions but don’t show
** avolition: total lack of motivation
2) social or occupational dysfunction
- significant portinon of time since onset of disorder
- ≥ 1 major area of functioning: work, interpersonal relations, self-care below level prior to onset
3) duration
- continuous signs of disorder for at least 6 months
- include at least 1 month of symptoms in first criteria
- prodromal or residual symptoms
4) excluded Schizoaffective or mood disorder
5) disorder not due to mental disorder or substance abuse
6) if history of pervasive developmental disorder present then at least 1 month of hallucination/delusions
components for Schizophrenia diagnosis
1) history of presenting illness
2) psychiatric history: neurosis, psychosis
3) substance use history
4) complete medical history and medication history
5) family, social, forensic, developmental, occupational history
6) physical and neurologic exam
7) mental state exam (MSE)
- suicidal homicidal ideation and risk
- reassess MSE on every interview
8) lab and other investigations
lab and other investigations for Schizophrenia diagnosis
1) vital signs
2) weight and BMI
3) FBC, SCr, LFT, TFT, ECG, lipid panel (antipsychotics increase BG and TG), urine toxicology
4) PGx for CYP2D6 and CYP2C19 for dose titration
non-pharmacological for Schizophrenia
1) individual cognitive behaviour therapy (CBT)
- conjunction w medication and family intervention
- process thoughts and understand why patients feels a certain way
2) neurostimulation
- electroconvulsive therapy (ECT)
** for treatment-resistant Schizophrenia - Repetitive transcranial magnetic stimulation
** reduce auditory hallucination
3) psychosocial rehabilitation programmes
- help improve adaptive functioning
tldr phases of Schizophrenia treatment
1) acute stabilistation
2) stabilisation
3) stable/maintenance phase
acute stabilisation phase for Schizophrenia
- reduce acute symptoms (reduce agitation/aggression/hostility, improve sleep)
- remove threat to self and others
- if acutely agitated/aggressive
** de-escalate
** consider oral antipsychotics +/- benzodiazepine
** if refuse/not possible to administer antipsychotic then fast acting IM alternative w monitoring
- monitor for treatment-emergent AE
** dystonia, pseudo-parkinsonism SE, vitals
stabilisation phase for Schizophrenia
- minimise/prevent relapse
- promote medication adherence
- optimise dose and manage AE
stable/maintenance phase for Schizophrenia
- improve functioning and QoL
- maintain baseline functioning
- optimise dose vs AE
- monitor for prodromal symptoms of relapse
- monitor and manage SE
types of typical antipsychotics (FGA)
- chlorpromazine (CPZ)
- haloperidol (Halo)
MOA of FGA
- block mesolimbic tract
** block D2 receptor -> block dopamine mesolimbic (ML) tract -> block overactivity in region causing positive symptoms
** tranquilise patient wo impairing consciousness + wo causing paradoxical excitement - block 3 other dopamine pathways that result in AE
1) mesocortical (MC) tract
** responsible for higher-order thinking and executive functions
** dopamine blockade = negative symptoms
2) nigrostriatal (NS) tract
** responsible for body movement
** dopamine blockade = EPSE
3) tuberoinfundibular (TI) Tract
** responsible for prolactin secretion
** dopamine blockade = hyperprolactinemia
types of atypical antipsychotics (SGA)
- aripriprazole (Ari)
- clozapine (cloz)
- olanzapine (Olan)
- quetiapine (Quet)
- risperidone (Risp)
- amisulpride
MOA of SGA
- mesolimbic tract (same as FGA)
- greater affinity at 5-HT2A -> block the other 3 tracts to lesser extent -> lesser EPSE
- more metabolic SE so need monitor
receptor affected vs effects
1) D2 antagonism
- improve positive symptoms
- SE: EPSE, hyperprolactinemia
2) 5-HT1A agonism
- anxiolytic
3) 5-HT2A antagonism
- antidepressant, improve negative symptoms, antipsychotic effects
4) 5-HT2C antagonism
- SE: weight gain
5) H1 antagonism
- SE: sedation, weight gain
6) alpha 1 antagonism
- SE: orthostasis, sedation
7) M1 antagonism
- SE: memory dysfunction, peripheral anticholinergic effect
8) IKr antagonism
- SE: QTc prolongation (pro-arrhythmic)
treatment algorithm for Schizophrenia
1) diagnosis
2) use single FGA/SGA (except clozapine)
- if adequate response, no intolerable SE, compliant then continue treatment
3) if CMI then switch to another FGA/SGA except clozapine
- if adequate response, no intolerable SE, compliant then continue treatment
4) if CMI then consider
- clozapine monotherapy
** when to start?
a) treatment resistant schizophrenia: failed ≥ 2 adequate trials of different antipsychotics
b) completed mandatory haematological monitoring every wk for 18 wks
c) treatment refractory evluation
** if adequate response, no intolerable SE, compliant then continue treatment - clozapine + augmenting agent (FGA/SGA/ECT)
- combination therapy
** if refusal/intolerable SE to clozapine
** possible combinations
a) 2 antipsychotics
b) antipsychotics + ECT/ other agents (mood stabilisers)
dosing and efficacy of antipsychotics
1) haloperidol
- very potent so low dose to exert effect
2) quetiapine
- less potent than haloperidol so higher dose to exert effect
3) olanzapine
- as potent as haloperidol but weaker D2 antagonism to mid potency D2 antagonist
4) clozapine
- split dose to BD to prevent seizure/severe hypotension
5) risperidone
- most commonly used, potent SGA so serotonergic modulation as well
precautions for Schizophrenia therapy
1) CVD
- QTc prolongation
- ECG required esp if CVS risk factors/personal history
2) PD
- EPSE worsened by antipsychotics
3) epilepsy and conditions predisposing to seizure
4) depression
5) myasthenia gravis, prostatic hypertrophy, angle-closure glaucoma
6) severe respiratory disease
7) history of jaundice
8) blood dyscrasia (Esp clozapine)
9) elderly w dementia
antipsychotics PK
1) mostly rapidly absorbed and fast onset
- except brexiprazole, olanzapine, aripiprazole
2) mostly have long t1/2 so can OD dosing
- except amisulpride, clozapine, quetiapine, ziprasidone
- need to inquire risk of hypotension and seizure
- OD dosing at night cuz sedative effect
3) lurasidone/ziprasidone w/after food increase F
TLDR antipsychotic SE
1) EPSE
2) hyperprolactinemia
3) metabolic
4) CVS
5) CNS
6) hepatic
7) ophthalmologic
8) dermatological
9) haematological
