ic11 schizophrenia Flashcards
what are the diagnoses associated with psychotic symptoms?
organic disorders:
- CNS: infections, epilepsy, dementia, parkinsons.
- Head: trauma, tumours/malignancy.
- Endocrine: hypo/hyperthyroidism
- Drug or substance abuse related
- Iatrogenic causes
- metabolic disorders/physiological disturbances affected nervous system.
affective disorders:
- mania, psychotic depression, postpartum depression
drugs associated with drug-induced psychosis (examples)
alcohol
barbiturates (eg phenobarbital)
benzodiazepines
beta blockers (eg propanolol)
corticosteroids
cns stimulants (amphetamines)
dopamine agonists (levodopa, for PD)
what is the dsm5 criteria for diagnosis of schizophrenia?
at least 2 of the following for at least 1 month
- disorganised speech
- catatonic behaviour (two extremes)
- hallucinations
- negative symptoms (affective flattening, avoilition)
- delusions
symptoms for more than 6 months
social or occupational dysfunctional
rule out medical disorders or substance abuse.
what are the labs and monitoring prior to diagnosis and treatment
almost all labs to rule out any general medical conditions or substance induced psychosis.
FBC
TFT
LFT
kidney function U/E/Cr
FBG
Lipids
ECG
urine toxicology
non phx interventions for schizophrenia
Psychosocial rehab: to help with adaptive behaviour/function
Support, counselling (incl vocational sheltered)
CBT: individual and group (eg family members)
ECT: electroconvulsive therapy
rTMS: repetitive transcranial magnetic stimulation
when is ECT used in schizophrenia?
for treatment resistant schizophrenia
when is rTMS used in schizophrenia?
may be used to help with auditory hallucinations.
mechanism of dopamine antagonism and the additional adverse effects of antipsychotics?
1) mesolimbic tract
- positive symptoms
ADR
2) mesocortical tract
- cause negative symptoms (region of higher order thinking and executive functions)
3) nigrostriatal tract
- EPSE
4) tuberofundibular tract
- hyperprolactinemia (anterior pituitary blockade)
receptor affinities and associated clinical implications (therapeutic and side effects)
D2
- antagonism: improve positive symptoms
- side effects: EPSE, hyperprolactinemia
5HT2A
- antagonism: possibly antidepressant effects, improve negative symptoms(?)
5HT2C
- antagonism side effects: weight gain
H1
- antagonism side effects: sedation, weight gain
alpha 1
- antagonism side effects: orthostatic hypotension
M1
- antagonism side effects: memory dysfunction, peripheral anticholinergic effect (constipation, dry mouth…)
what is the treatment algorithm for schizophrenia
1) FGA or SGA except clozapine
if inadequate or intolerable SE
2) FGA or SGA except clozapine
if inadequate or intolerable SE
3) Clozapine
4) Combination therapy:
- clozapine + FGA/SGA/ECT
- FGA + FGA
- FGA + SGA
- FGA/SGA + ECT
should have adequate response, no intolerable side effects, and compliant
how long should treatment be initiated for schizophrenia before swapping to another agent?
atleast 2-6 weeks at OPTIMAL therapeutic doses
(except clozapine up to 3 months for mono therapy; 8-10 wks for combination)
treatment considerations if patient is non-compliant?
consider long acting injectable antipsychotics
- iM risperidone microspheres, paliperidone, aripiprazole, haloperidol decanoate, flupenthixol decanoate, zuclopenthixol decanoate.
what tx can be considered for acute agitation (where patient is cooperative)?
consider
1) oral lorazepam 1-2mg
2) oral antipsychotic
- halo 2-5mg tab/sol with pre tx ecg
- risp orodispersible tab/sol 1-2mg
- quetiapine IR tab 50-100mg
- olanzapine orodispersible tab 5-10mg
what tx can be considered for acute agitation (where patient is uncooperative)?
1) fast acting
IM lorazepam 1-2mg
2) antipsychotic
- IM olanzapine, aripiprazole, haloperidol, promethazine
what tx can be considered for catatonia (abnormal movement/behaviour, withdrawal)
po/im lorazepam
or ECT
what tx can be considered for depressive sx or negative sx
depression: antidepressant
negative symptoms: mild/moderate efficacy antidepressant
which oral antipsychotics have poor Tmax >3h (less rapidly absorbed and or slower onset)
aripiprazole
brexpiprzole
olanzapine
which oral antipsychotics have shorter t1/2 (will require divided dosing)
chlorpromazine
sulpiride
amisulpride
clozapine
quetiapine
ziprasidone
which antipsychotics can be given with food to increase BA
lurasidone
ziprasidone
what are the EPSE side effects and their characteristics?
fast onset (hours to weeks)
1) dystonia: muscle spasms (mins to hours)
2) akathisia: restlessness
3) pseudo-parkinsonism: dyskinesia, tremors, rigidity, salivation..
late onset
4) tardive dyskinesia: orofacial movements, tongue protrusions (IRREVERSIBLE)
what are the risks and management of dystonia caused by antipsychotics?
associated with high potency antipsychotics
lower dose or switch to SGA
manage with IM anticholinergics: benzatropine, diphenhydramine
what are the risks and management of pseudo-parkinsonism caused by antipsychotics?
higher likelihood in elderly females and previous neurological damage (stroke, head injury)
lower dose or switch to SGA
manage with benztropine or trihexyphenidyl (benzhexol)
what are the risks and management of akathasia caused by antipsychotics?
associated with high potency antipsychotics
FGA> risp > olan >quetiapine, clozapine
Lower dose or switch to SGA
anticholinergics are not effective
consider
clonazepam PRN or
propanol 20mg TDS (max 160mg/day)
what are the risks and management of tardive dyskinesia caused by antipsychotics?
FGA > SGA
WORSENS WITH ANTICHOLINERGICS
DISCONTINUE any anticholinergics
lower dose or switch to SGA
consider:
- reversible vesicular monoamine transporter 2 (VMAT2): valbenazine 40-80mg/day
- clonazepam PRN
what are the risks and management of HYPERPROLACTINAEMIA caused by antipsychotics?
FGA > pali > risp > SGA
decrease dose of drug
consider switching to aripiprazole OR
use dopamine agonist (amantadine, bromocriptine)
manifestations of hyperprolactinaemia?
males
decrease libido
galactorrhea or amenorrhea
male:
gynaecomastia
what are the risks and management of metabolic disorders caused by antipsychotics?
risk:
high: olanzapine, clozapine
mid: risp, quet, cpz
low: brex, ari, lura, cariprazine, zipra, haloperidol
management:
- change to lower risk agents
- lifestyle modification: diet and exercise
- treat diabetes with eg metformin AND hyperlipidaemia
what are the manifestations of metabolic disorders?
increase FBG, diabetes
increased lipids
weight gain
what are the risks and management of orthostatic hypotension caused by antipsychotics?
risk:
- CPZ, Clozapine > Risp, pali, quetiapine > olan, lura, ari, sulpiride (choose these)
get up slowly from a sitting or lying position
switch to lower risk agents.
what are the risks and management of QTC prolongation caused by antipsychotics?
risk:
high doses, IV haloperidol, decreased serum k+, IHD, female gender
thioridazine > CPZ > ziprasidone > halo > ilo > quet > risp > olan
if qtc >440ms (male), >470ms (female) = switch to lower risk agent
if qtc >500ms, refer to cardiologist
what are the risks and management of VTE/PE caused by antipsychotics?
low potency FGA (CPZ)
prevent monitor and treat
what are the risks and management of sedation caused by antipsychotics?
CPZ, clozapine > quetiapine > olanzapine
consider amisulpride, aripiprazole, brexpiprazole, ziprasidone, paliperidone (switch to lower risk agents)
what are the risks and management of seizures caused by antipsychotics?
CPZ, clozapine > other antipsychotics (consider -dones, piprazoles)
also high doses, rapid titration, or history of epilepsy.
consider switching to high potency agents
what are the risks and management of NMS caused by antipsychotics?
high potency antipsychotics
management:
- IV dantrolene 50mg TDS
- oral dopamine agonist: amantadine, bromocriptine
- switch to SGA
what is the presentation of NMS
autonomic dysfunction: increase PR, labile BP, diaphoresis (sweating)
altered consciousness
increased CK
muscle rigidity
fever
what is the risk associated with anticholinergics + antipsychotics
psychogenic polydipsia (thirst)
temperature dysregulation
what are the risks and management of hepatic side effects caused by antipsychotics?
CPZ, quetiapine, olanzapine > other SGAs
if jaundice occurs, discontinue and switch
what are the hepatic side effects:
increased LFTs
cholestatic jaundice
what are the risks and management of opthamologic side effects caused by antipsychotics?
phenothiazines (CPZ, thioridazine), quetiapine
if on QUET: EYE exam q6months
what are the ophthalmologic side effects:
cornea, lens changes
pigmentary retinopathy
what are the dermatological side effects
maculopapular rash
photosensitivity
pigmentation
what are the risks and management of DERM SE caused by antipsychotics?
phenothiazines
protective clothing or switch to another agent
what are the risk associated with clozapine?
may decrease WBC and ANC and cause agranulocytosis
discontinue if severe: WBC<3x10^9 or ANC <1.5x10^9
what are the parameters to monitor for antipsychotics
x7
Metabolic:
- BMI, Waist circumference, FBG, Lipid
Plasma prolactin
BP
EPSE exam
how often to monitor for BMI?
WEEKLY x 6 wks
OR
EVERY VISIT (at least monthly) x3-6 months (3mth for SGA)
Q3months when dose stabilised
how often to monitor for waist circumference
EVERY VISIT x 6 months
then
ANNUAL
how often to monitor for FBG
low risk: annual
high risk: 4 months from initiation (3 months if SGA), then annually
how often to monitor for LIPIDS
low risk: q2-5 years
high risk: 3 months after initiation (SGA), THEN Q6 MONTHS
how often to monitor for PLASMA PROLACTIN
at baseline
how often to monitor for BP
3 months after initiation
THEN
ANNUALLY
how often to monitor for EPSE
q weekly x 2 weeks OR until dose stabilised
low risk: q6mth (FGA), q12mth (SGA)
high risk: q3 mth (FGA), 12mth (SGA)
how often and wat to monitor for side effects in clozapine
WBC and ANC for leucopenia and/or agranulocytosis
weekly x 18 weeks
then monthly
what to monitor specifically for ziprasidone
QTC prolongation
do ECG
repeat if risk of symptoms like syncope.
what antipsychotics to choose for pregnancy
clozapine
olanzapine
what antipsychotics to choose for breastfeeding
olanzapine
quetiapine
continue clozapine and stop breastfeeding
what antipsychotics to choose for hepatic impairment
amisulpride and sulpiride
RENALLY CLEARED
what antipsychotics to choose for renal impairment
aripiprazole PO
DO NOT USE AMISULPRIDE OR SULPIRIDE
WHAT to caution and treatment planning for elderly on antipsychotics
consider drugs with high alpha adrenergic and anticholinergic side effects
start low go slow, simplify, and avoid long t1/2 drugs
risk of increased mortality and CVAs in dementia patients on FGA / SGA.
what is one pertinent drug disease to caution
drug disease: antipsychotics will worsen PD
what are substrates of cyp1a2
1a2 substrate
phenothiazines
halo
olan
zipra
clozapine
1a2 inhibitors and inducers
ia2 inducers: rifampicin, phenobarbital, phenytoin, cigarette smoke
1a2 inhibitors: fluvoxamine, macrolides, quinolones, isoniazid, ketoconazole
cyp 2d6 substrates?
phenothiazines
halo
olan
risp
aripiprazole
brexpiprazole
2d6 inhibitors and inducers
2d6 inhibitors: fluoxetine, paroxetine, bupropion, duloxetine
2d6 inducer: rifampicin, phenobarbital, phenytoin, cbz
3a4 substrates for antipsychotics
lumateperone (CONTRA)
lura (CONTRA)
quet
cariprazine
risp
ari
brex
3a4 inhibitors?
3a4 inhibitors: macrolides, azoles, grapefruit juice, fluvoxamine, norfluoxetine, TCA, imidazole, isoniazid
3a4 inducers: CBZ, phenytoin, barbiturates
what drugs will have additive cns effects
cns depressants
- alcohol, opioids, psychotropics like benzodiazepine
what drugs will have additive adverse effects
antimuscarinics, antihistaminic, alpha1 adrenergic blockade, dopamine blockade
what drugs will antagonise antipsychotics
dopamine agonists
levodopa
bromocriptine
What drugs will increase hypotensive effects
antihypertensives,
trazodone (SARI)
what happens with adrenaline + antipsychotic combination
pressor effects reversed by CPZ or other low potency antipsychotics
what will increase the toxicity and alter response of antipsychotics
TCAs
what may cause neurotoxicity
lithium
what drug with special interaction with clozapine?
carbamazepine maybe increase risk of agranulocytosis
what is the time course of treatment response?
early:
1st week: decreased agitation, aggression, hostility
2nd-4th week: decrease hallucinations, paranoia, bizarre behaviors
improved organisation in thinking
late:
6-12 weeks: decreased delusions, possibly negative symptoms may improve
