L12 Schizophrenia Flashcards
subsidised schizo drugs
- older gen
- resperidone: v potent and effective
- olanzapine
- clozapine
is aripiprazole subsidised?
no!
diagnoses with assoc psychotic sx
organic disorders (iatrogenic causes, psychosis related to alc and psychoactive substance misuse), affective disorders presenting w psychotic sx, schizophrenia (schizotypal personality disorder or delusional disorder)
quetiapine
very weak dopamine antagonist, can be used for psychotic sx a/w PD - will not worsen PD sx so much
etiology of schizophrenia
- predisposing: genetics, neurodevelopmental effects
- precipitating: drugs
- perpetuating: lack of support, poor adherance w antipsychotic medications
CBT is recommended for
- preventing psychosis in ‘at risk’ group; refer to psychiatrist if a person has transient/attenuated psychotic sx causing distress/impairment
- first episode psychosis: assess for ptsd
- schizophrenia
ECT is recommended for
- reserved for tx-resistent schizophrenia, esp catatonic sx
psychosocial rehabilitation program: vocational shelter
employment, rehabilitation
- improve pt’s adaptive functioning
What must you assess prior to schizophrenia diagnosis and tx?
MSE: suicidal/homicidal ideations and risks
accurate diagnosis of schizophrenia include exclusion that the disorder is due to
medical disorder or substance abuse
DSM-5 criteria:
2 or more of the following, each persisting for a significant portion of at least 1 month:
- delusions
- hallucinations
- disorganised speech
- grossly disorganised or catatonic behavior
- neg sx
signs of disorders must be
continuous, at least 6 months
therapeutic goals
- minimise threat to self and others
- minimise acute sx
- prevent relapse
- medication adherence
- optimise dose vs adverse effects
- improve functioning and QOL
in short term, antipsychotic medications are used to
calm disturbed patients
- whatever the underlying psychopathology which may be: schizophrenia, mania, toxic delirium, or agitated depression
antipsychotics for schizophrenia
relieve sx of psychosis such as thought disorder, delusions, hallucinations + prevent relapse:
- less effective in apathetic withdrawn pts
- pt w acute sx of schizophrenia generally respond better than those w chronic sx
antipsychotics for schizophrenia: acute or LT tx?
LT tx often necessary after the first ep of psychosis and prevent illness from becoming chronic
- a pt who is maintaining well on an antipsychotic may relapse if tx is withdrawn inappropriately
- psychotic sx may persisnt continuously in 5-15% of pt: poor response to FGA
relapse upon discontinuation of antipsychotics
often delayed for several weeks after cessation of tx
- adipose tissue acts as depot reservoir after chronic regular usage of antipsychotics
- antipsychotics stored in fat cells then diffuses back into bloodstream after tx cessation, until depletion
methods to overcome poor treatment adherance
- IM LA inj
- community psychiatric nurse: conduct home visits to pill count/adm meds
- patient and family (caregiver) education: supervision/monitoring
the central dopamine systems is composed of the following 4 tracts
- mesolimbic
- mesocortical
- nigrostriatal
- tuberoinfundibular
antipsychotics
dopamine receptor antagonist
mesolimbic tract
blockade of dopamine receptors in this tract is probably the common MOA for all antipsychotics
- overactivity in this region is responsible for pos sx of schizophrenia
blockade of which dopamine tracts causes adverse effects?
mesocortical, nigrostriatal, tuberoinfundibular
tuburoinfundibular tract
dopamine blockage in this region of the anterior pituitary leads to hyperprolactinemia
- unopposed secretion of prolactin into bloodstream
- can cause osteoporesis, sexual dysfunction, gynaecomastia (painful)
mesocortical tract
responsible for higher-order thinking and executive functions
- dopamine blockade or hypofunction in this region results in neg sx (can sometimes manifest as depression, hard to differentiate)
nigrostriatal tract
modulates body movement
- antipsychotic-induced dopamine blockade in this region causes EPS
- rest tremor, cogwheel rigidity, oculogenic crisis (eyebrall rolling up), dyskinesia (involutary mvement of tongue or jaw, grimacing)
D2 antagonism effects
- improve pos sx
- EPSE, hyperprolactinemia
5HT2a antagonism effects
antidepressant effects? improve neg sx? antipsychotic effects?
5HT2c antagonism effects
weight gain
H1 antagonism effects
sedation/weight gain
a1 antagonism
orthostasis (postural hypoTN), sedation
M1 antagonism
memory dysfunction, peripheral anticholinergic effects (dry mouth, constipation - drugs given for hand tremors SE of antipsychotics eg benzhexol/benztropine)
IKr antagonism
QTc interval prolongation (pro-arrhythmic)
- may result in cardiac death
- don’t start tx unless clear of indication and diagnosis
what drug is used for tx-resistant schizo (failed more than 2 adequate trials of different antipsychotics, at least 1 should be a SGA)?
clozapine
- fbc monthly, w ANC
medication selection is
individualised for a pt
- based on physician’s assessment of clinical circumstances, past response/failures on antipsychotics, patients needs, efficacy and side effect profiles of the therapy
pt req compliance to an adequate trial of antipsychotic (excl clozapine) of _____ and ____ before being considered as ‘non-responders’ to the medication
- at least 2-6 weeks
- at optimal therapeutic doses
Examples of LA injectable antipsychotics
- IM resperidone micropsheres
- IM paliperidone prolonged release suspension
- IM aripriprazole LAI
- IM halperidol decanoate
- IM fluphenthixol decanoate
- IM zuclopenthixol decanoate
pharmacological tx of schizo usually mono/multi therapy?
mono
precautions to antipsychotic use, esp for clozapine
blood dyscrasis: infection (fever, cough, sore throat) is a risk factor
precautions to antipsychotic use
cv disease, PD, PH, angle-closure glaucoma, severe respiratory disease, blood dyscrasias, elderly w dementia
which fast-acting IM inj is most commonly used?
haloperidol decanoate, cheapest
acute agitation - cooperative pt
lorazepam, risperidone
acute agitation - uncooperative
im lorazepam, olanzapine, aripiprazole, haloperidol, promethazine
- can halo+lora too
catatonia behaviours pharmaco tx`
benzodiazepines: po/im lorazepam
which antipsychotics must be adm w food
lurasidone, ziprasidone
which antipsychotics cannot be taken OD
chlorpromazine, clozapine, quetiapine
SGA wo weight gain SE
ziprasidone, aripiprazole, brexipiprazole, lurasidone
- ‘-ones’ or ‘-piprazoles’: less sedating, less weight gain
SGA w most weight gain SE
clozapine, olanzapine
- ‘-ines’: more sedaing, more weight gain
how to manage dystonia SE from high potency antipsychotics?
IM anticholinergics eg benztropine, diphenhydramine (relax muscles)
how to manage psuedo-parkinsonism SE for elderly female w previous neurological damage?
- decr antipsychotic dose, or switch to SGA (quet,sulp)
- anticholinergic PRN eg benzhexol (aka trihexyphenidyl, some abuse potential) < benztropine (long acting)
how to manage akathisia SE from high potency antipsychotics?
- decr antipsychotic dose, or switch to SGA
- clonazepam or lorazepam (low dose), prn
- propranolol 20mg tds (max 160mg/d)
- anticholinergics generally unhelpful
how to manage tardive dyskinesia SE from FGA?
- discontinue any anticholinergics
- decr antipsychotic dose, or switch to SGA (clozapine possibly effective)
- reversible inhibitor of vesicular monoamine transporter 2 (VMAT2): valbenazine 40-80mg/day
- clonazepam prn
how to manage hyperprolactinaemia SE from FGA?
- decr FGA dose
- dopamine agonist (eg. amantadine, bromocriptine)
- switch to aripiprazole (partial agonist of d2 receptor, reverse effects a little)
how to manage metabolic SE?
- lifestyle modification - diet, exercise
- treat diabetes eg w metformin
- treat hyperlipidemia
- switch to lower risk agents
antipsychotics w high risk of metabolic SE
olan, cloz
antipsychotics w low risk of metabolic SE
ari, lura, halo, brexi, zipra
RVMT2 inhibitor
valbenzine, reversible
switch to high potency antipsychotics for which SEs
VTE/PE, seizure
NMS sx
muscle rigidity, fever, autonomic dysfunction (incr PR, labile BP, diaphoresis), altered cosnciousness, incr CK by 10,000s, lead-pipe rigidity
NMS risk factors
- high potency antipsychotics
- non compliant/abrupt stop of PD drugs, as if taking a sudden high potency of d2 block
NMS tx
- IV dantrolene 50mg TDS (smooth muscle relaxant)
- oral dopamine agonist eg amantadine, bromocriptone
- supportive measures
- switch to SGA, w lower potency
adj tx
benzo (agitation), antide (dep)
daytime sedation SE mgmt
- adm dose in early evening eg 7pm for sedation to wear off
- consolidate once-nightly dosing whenever possible (except cloz and quet)
dizziness SE mgmt
rise up slowly from lying/sitting position (orthostatic hypotension)
monitoring SE
- weight gain: BMI, q3 months
- DM: FPG, q3mths then annually
- HLD: lipid pannel
- hypo/hyperTN: BP, q3 months after initiation, then annually
- EPSE: EPSE exam for rigidity,tremors,akathisia,tardive dyskinesia
- leucopenia/agranulocytosis: WBC and ANC (cloz), weekly for first 18 weeks, then monthly
pregnancy
ola, cloz: watch for gestational dm
breastfeeding
- olz, que: suitable
- pt on cloz should cont on drug and not breastfeed
renal impairment
- oral aripi preferred
- avoid sul, amisul
hepatic impairment
sul,amisul preferred
elderly
- avoid drugs w high propensity for a1 adrenergic blockade (orthostatic hypoTN)
- or anticholinergic SE (constipation, urinary retention, delirium)
- start low, go slow
- simplify regime
- avoid adverse interactions
- avoid long t1/2 drugs
- precautions: FGAs and SGAs reported to incr mortality and CVAs in dementia pt
when will we see improvements in decr paranoia, hallucinations, bizarre behaviours + improved organisation in thinking
2-4wks
Antipsychotics effect threshold
60% D2 receptor blockade
Prolactin threshold
70% D2 receptor blockade
EPS threshold
80% D2 receptor blockade
