Schizophrenia NBT Flashcards
what is the definition of psychosis?
- acute and severe mental condition
- lack of insight; out of touch with reality
how is schizophrenia different from psychosis?
schizophrenia: more common forms of psychosis
- disorganised and bizzare thoughts, delusions, hallucinations, impaired psychosocial functioning
- higher incidence of comorbid conditions including HTN, DM, cardiac conditions, substance abuse disorders
- mortality higher
- onset: commonly adolescence or early adulthood
what are the different diagnoses/disorders with associated psychotic sx?
- organic disorders
- Iatrogenic causes (drug related causes e.g. levodopa/dopamine agonist)
- Psychosis related to alcohol & psychoactive substance misuse (e.g. methamphetamine or other CNS stimulants or alcohol/cocaine withdrawal)
- epilepsy
- cerebral lesions (tumors, stroke, trauma)
- CNS infections; genetic/congenital
- parkinson’s disease
- dementia
- any metabolic disorders affecting nervous system
- endocrine disorders - affective disorders presenting with psychotic smx: mania, psychotic depression, post-partum psychosis
- Schizophrenia itself
- psychosis due to psychological development disorders or stress-related reactions
which neurotransmitters are dysregulated which can cause schizophrenia?
- dopaminergic (DA)
- serotonergic (5ht)
- glutamatergic function
what are the etiology factors of schizophrenia?
- predisposing (factors from early life determining a person’s vulnerability to precipitating factors)
- genetics (possible linkage)
- neurodevelopmental effects - precipitating (events that occur shortly before onset of disorder)
- Drugs = alcohol, BZDs, barbiturates, dopamine agonist (levodopa)
- CNS injury - Perpetuating (factors that prolong course of disorder)
- lack of support
- poor adherence with antipsychotic medications
Most common reason admitted into hospital = substance/withdrawal, non-compliance)
what is the clinical presentation of schizophrenia based on the DSM-5 criteria (no need to memorise)
- two or more of the following, where each for at least a 1-month period:
a. delusions
b. hallucinations
c. disorganised speech
d. grossly disorganised or catatonic behaviour
e. negative symptoms (affective flattening - zero expression on face; avolition - loss of motivation = can affect compliance) - social/occupational dysfunction
- duration
- continuous signs of the disorder for at least 6 months (inclusive of the 1 month sx in (1)) - schizoaffective or mood disorder has been excluded
- disorder NOT due to medical disorder or substance use
- if have pervasive development disorder, must have sx of hallucinations or delusions present for at least 1 mth
how to we diagnose/assess schizophrenia?
- Hx of present illness
- psychiatric Hx: any hx of neurosis or psychosis
- substance use hx: past use of cigarettes/ETOH/substances
- complete medical hx & medication hx
- other med used
- reassess adherence to med every visit - family, social, developmental, occupational hx
- esp 1st-degree family hx (as med they were taking could work for the pt) - physical & neurological exam
- mental state exam (mse) [for accurate diagnosis]
- assess for suicidal/homicidal ideations and risk
- reassess MSE on every interview to evaluate efficacy & tolerability - labs & other investigations
- to exclude general medical conditions or substance-induced sx (e.g. depression, mania, anxiety, insomia, psychosis)
- if patient have hx of unprotected sex: neurosyphilis (CNS infection) = check for WBC
- fasting blood glucose for the 2nd gen anti-psy
- urine toxicology for any substances
- ensure electrolytes are balanced
- ensure kidney is functioning
what is the non-pharmacological treatment?
-
individual cognitive behavioural therapy (CBT)
- in conjunct with med
- can prevent psychosis in ‘at risk’ groups
- …
2, electroconvulsive therapy (ECT)
- reserved for treatment-resistant schizophrenia
- repetitive transcranial magnetic stimulation (rTMS)
- effective for reducing auditory hallucinations in schizophrenia -
Psychosocial rehabilitation
- improve patient’s adaptive functioning
- e.g. vocational: employment
- CBT included
- supportive/ counselling
what are the therapeutic goals of schizophrenia?
- acute stabilisation
- minimise threat to self and others
- minimise acute symptoms - stabilisation
- prevent relapse
- promote medication adherence
- optimize dose vs adverse effect - Stable/maintenance phase
- improve functioning and QOL
- monitor for adverse effect (e.g. tardive dyskinesia)
why is maintaining antipsychotic treatment important?
- reduces risk of relapse in stable illness to <30% per year
- if w/o maintenance therapy:
- -> 60-70% patients relapse within 1 yr
- -> 90% patients relapse within 2 yrs
what are key things to take note for pharmacological treatment of schizophrenia?
- antipsychotic med = aka neuroleptic
- tranquilizes w/o impairing consciousness and w/o paradoxical excitement - short term: calm disturbed patients
- commonly used for schizophrenia (can be used for acute mania, agitated depression, toxic delirium)
- antipsychotics relieve symptoms of psychosis such as thought disorder, hallucinations and delusions, and prevent relapse
- long term treatment often necessary after first episode of psychosis and prevent illness from becoming chronic
- relapse often delayed for several weeks after cessation of treatment
- -> adipose tissue are depot reservoir after chronic regular usage of antipsychotic
- Method to overcome poor treatment adherence:
a. IM long-acting injections
b. community psychiatric nurse (to adminster pills for them)
c. patient and family (caregiver) education (to monitor them)
- Method to overcome poor treatment adherence:
what is the MOA of antipsychotics?
- Mesolimbic tract
- blockade of dopamine receptors the most common MOA for all antipsychotics
- as overactivity in this region is responsible for positive symptoms of schizophrenia - Mesocortical tract (MC) tract
- responsible for higher-order thinking and executive functions
- dopamine blockade/ hypofunction here results in negative symptoms - Nigrostriatal (NS) tract:
- modulates body movement
- dopamine blockade here causes EPSE - Tuberinfundibular (TI) tract
- dopamine blockade of the anterior pituitary leads to hyperprolactinemia
which tract when blocked reduces the positive symptoms of schizophrenia?
Mesolimbic tract
which tract when blocked reduces the negative symptoms of schizophrenia?
Mesocortical tract
which tract when blocked reduces the extrapyramidal SE?
Nigrostriatal tract
which tract when blocked reduces gynecomastia, osteoporosis, sexual dysfunction, hyperprolactinemia?
Tuberoinfundibular tract
which receptor when antagonises improves the positive symptoms of schizophrenia?
D2 receptor antagonism
what are the side effects of D2 antagonism
D2 antagonism: EPSE, hyperprolactinemia
what is the therapeutic effect of 5-HT1A agonism?
anxiolytic
which receptor when antagonises improves the negative symptoms of schizophrenia?
5-HT2A
which drugs have more of the 5-HT2A antagonism?
the SGA (2nd gen anti-psy): aripiprazole, clozapine, risperidone
what SE does H1 antagonism cause?
sedation/weight gain
what SE does a1 antagonism cause
orthostasis (postural hypotension), sedation
what SE does 5-HT2C antagonism causes?
weight gain
what SE does M1 antagonism causes?
memory dysfunction, peripheral anticholinergic effects
what does IKr antagonism causes?
IKr = rapid delayed rectifier
QTc interval prolongation (pro-arrhythmic)
what is the hypothetical threshold for the anti-psychotic drug effects (D2 receptor blockade)
at 60% D2 receptor blockade: anti-psychotic effect threshold
at 70%: prolactin threshold
at 80%: EPS threshold
anti-psy that have weaker affinity can reach the anti-psy effect threshold vs high affinity anti-psy like haloperidol can reach the EPS threshold
–> thus v hard to know where is the threshold
what is the algorithm for schizophrenia treatment?
After diagnosis of schizophrenia:
- use single FGA or SGA (except clozapine)
if inadequate or no response/intolerable SE
2. use another single FGA or SGA (except clozapine) that was not prev tried
if still inadequate or no response/intolerable SE
- Clozapine = for treatment-resistant schizophrenia
- -> 1% of granulocytosis –> death –> thus need to monitor full blood count - Clozapine + (FGA or SGA or electroconvulsive therapy [ECT]) or
- (FGA + FGA or SGA + SGA) + either ECT or other agent (e.g. mood stabiliser)
how is the initial anti-psy med chosen for the patient?
- individualised based on past response/failures on antipsychotics, efficacy and SE profiles of the therapy
what do we need to do to ensure that the antipsychotic drug used is working before changing it to another drug?
1- patient need to be compliant to the antipsychotic (except clozapine) for at least 2-6 weeks at optimal therapeutic doses before being considered as non-responder
2- if on clozapine: 3 months to confirm therapeutic response
3- if on clozapine + another anti-psy: 8-10 weeks required to confirm therapeutic response
4- manage any intolerable SE accordingly or switch to more suitable alternatives
IMPORTANT What dosage form should we consider when a patient is not completely compliant to the drug?
consider long-acting injectable antipsychotic if inadequately compliant, or if patient prefers (e.g. cannot swallow)
what are the long-acting IM anti-psychotics?
All IM: SGA 1. Risperidone microspheres 2. Paliperidone prolong release suspension 3. Aripiprazole LAI
FGA
- Haloperidol decanote
- Flupenthixol Decanoate
- Zuclopenthixol decanote
When can we consider giving clozapine as an anti-psy
only to those who are treatment-resistant
def: those who had failed >= 2 adequate trials of different antipsychotics (at least 1 should be a SGA)
what has to be monitored when a patient is on clozapine?
routine haematological monitoring
in sg: weekly for first 18 weeks, then monthly
monitor for WBC and ANC - leucopenia/agranulocytosis
(a treatment-refractory evaluation should be performed to reexamine diagnosis, substance abuse, medication adherence, and psychosocial stressors. CBT or psychosocial augmentation should be considered)
Which conditions we have to be pre-cautious about before the start of antipsychotic use?
-
CV disease
- CI: those with QTc prolongation
- ECG required in those with CV risk factors, personal hx of CV disease, or patient is being admitted as inpatient - Parkinson’s disease –> the EPS worsens by antipsychotic (can consider quetiapine as it is less likely to cause adverse drug-induced parkinsonism)
- Epilepsy & conditions predisposing to seizures
- depression
- myasthenia gravis
- prostatic hypertrophy
- angle-closure glaucoma
- severe resp disease
- Hx of jaundice
- Blood dyscrasias (blood disease) - esp for Clozapine
- Elderly with dementia - increased risk for mortality and stroke (black box warning)
in which patient antipsychotic use is a black box warning and needs to be documented with the family member?
elderly with dementia
what is the preferred drug for acute agitation (psychiatric emergency)?
1. if patient is cooperative: consider *oral* medication: (a) oral **lorazepam** 1-2mg or (b) oral antipsychotic: - Haloperidol - **Risperidone** - Quetiapine - Olanzapine or (c) oral-inhaled loxapine (CI in asthma/COPD)
(lorazepam or risperidone commonly used)
- if patient uncooperative and remains agitated/aggressive:
consider fast-acting IM injection
(a) IM Lorazepam 1-2mg or
(b) IM Olanzapine (not to be given with IM Lorazempam within 1h of each other)
(c) IM Aripiprazole (less hypotensive than IM Olanzapine)
(d) IM Haloperidol
(e) IM Promethazine
(f) (a) + (d)
(g) (d) + (e)
what drug can be given for catatonia?
(a group of symptoms that usually involve a lack of movement and communication, and also can include agitation, confusion, and restlessness. )
BZD: po/IM Lorazepam
what can be given for depressive sx and/or negative sx of chronic schizophrenia?
for depression: suitable antidepressant
for negative sx: some SSRIs have mild-moderate efficacy
which anti-psychotic drugs are to be taken with food?
- Lurasidone & Ziprasidone
which anti-psychotics are CYP3A4 metabolised?
FGA:
Chlorpromazine, Haloperidol,
SGA:
Aripiprazole, Brexpiprazole, Clozapine, Cariprazine, Olanzapine, Quetiapine, Lurasidone, Ziprasidone
NOT: risperidone, paliperidone
what are the FGA?
Chlorpromazine, Haloperidol, sulpride, trifluoperazine
(Note haloperidol v potent and dosed BD or TDS compared to most anti-psy which is OD)
(0.5-3mg BD/TDS, total dose/day is 5-15mg)
what are the SGA?
- Amisulpride
- Aripiprazole
- Brexpiprazole
- Cariprazine
- Clozapine (max dose 900mg/day v high)
- Lurasidone (w food)
- Olanzapine (5-20mg/day)
- Paliperidone
- Quetiapine (max dose 800mg/day vhigh)
- Risperidone (2-6mg/day)
- Ziprasidone (w food)
- Asenapine
what are the FGA IM long-acting antipsychotics
- Flupenthixol decanoate
- Haloperidol decanoate –> can cause high EPSE
- Zuclopenthixol decanoate
not that impt (grey):
Fluphenazine decanoate
what are the SGA IM long-acting antipsychotics?
- risperidone (every 2 weeks) (supplement with oral dose during 1st 3 weeks)
- Paliperidone PR suspension for injection (every 4 weeks or every 3 months)
- Aripiprazole ER suspension (every 4 weeks/ every month)
FGA have more of what side effects than SGA?
EPSE and increase prolactin
due to D2 block
Which SGA have weight gain as the most important SE?
Clozapine, Olanzapine
which SGA dont have the weight gain SE
- Lurasidone
- Ziprasidone
- Aripiprazole
- Brexipiprazole
how do we manage the EPSE (dystonia) SE?
- Dystonia: muscle spasms, stiffness
- caused by high-potent antipsy (e.g. haloperidol), neuroleptic-naive patients, young M
- thus, use IM anticholinergics (e.g. benztropine, diphenhydramine)
how do we manage the EPSE (Pseudo-parkinsonism) SE?
- pseudo-parkinsonism: tremors, rigidity, bradykinesia
- seen in elderly F, w prev neurological damage (head injury, stroke)
- thus, reduce antipsychotic dose (not v practical) or switch to SGA
- anticholinergics PRN (e.g. trihexyphenidyl (benzhexol), benztropine
how do we manage the EPSE (Akathisia) SE?
Akathisia - restlessness
- due to high potency antipsychotics (e.g. haloperidol) > Risp > Olan > Quetiapine/Clozapine
- management:
- -> reduce antipsy dose or switch to SGA
- -> clonazepam (low dose) PRN
- -> propranolol
- -> anticholinergics NOT helpful
how do we manage the EPSE (tardive dyskinesia) SE?
- irreversible, lip chewing, tongue protrusion
- due to:
- -> FGA > SGA
- -> worsen with anticholinergic drugs
- solution:
- -> discontinue any anticholinergics
- -> decrease antipsychotic dose, or switch to SGA (clozapine possibly effective)
- -> Valbenazine 40-80mg/day (reversible VMAT2 inhibitor)
- -> Clonazepam PRN
how do we manage the hyperprolactinemia SE?
- gynecomstia in Male, lactation
risk:
- FGAs, and
- Paliperidone > Risperidone > other SGAs
solution:
- decrease FGA dose
- dopamine agonist (amantadine, bromocriptine)
- switch to aripiprazole
how do we manage the metabolic SE?
- weight gain, diabetes, increase lipids
risk:
- high: Olanzapine. Clozapine
- moderate: chlorpromazine, quetiapine, risperidone
- low: Aripiprazole, Haloperidol, Lurasidone, Ziprasidone
solution:
- lifestyle modification: diet, exercise
- treat DM (e.g. w metformin), hyperlipidemia
- *switch to lower risk agents = ari, lura, zip, halo
what are the cardiovascular side effects of antipsychotics?
- orthostatic hypotension
- QTc prolongation
- VTE/PE
how does the CV SE of orthostatic hypotension occur? which drugs are higher risk?
- chlorpromazine, clozapine > Risperidone, Paliperidone, Quetiapine > Olanzapine, Ziprasidone, Aripiprazole, Sulpride
how can we manage orthostatic hypotension?
- switch to lower risk agents
- get up slowly from sitting or lying position
which drugs have a higher risk to cause QTc prolongation
Thio > chlorpromazine > Zip > Halo > iloperidone (llo) > Quet > Risp > Olanzapine
- high doses, IV haloperidol, decreased K+, IHD
how can we manage QTc prolongation?
if QTc > 440ms (for M) and >470ms (for F): switch to lower risk agents, refer cardio if >500ms
which drugs increase the risk of VTE/PE?
Low potency > SGA > FGA > high potency, Aripiprazole
how can we manage VTE/PE
manage emergent DVT
what are the CNS SE of antipsychotics?
- sedation
- seizure
- neuroleptic malignant syndrome (NMS)
- psychogenic polydipsia
- temperature dysregulation
which drugs have a higher risk of causing sedation?
chlorpromazine, cloz > quet > olan > risp, pali, zip, ari
how to manage the sedation SE?
switch to a lower risk agents
which drugs have a higher risk of causing seizure?
- cloz, chlorpromazine > other SGAs
- high doses, rapid titration, Hx of epilepsy
how to manage the seizure SE?
- switch to high-potency agents (e.g. halopiderol)
what is neuroleptic malignant syndrome (NMS) and which drugs have a higher risk of causing NMS?
- muscle rigidity, fever, autonomic dysfunction (increase PR, labile BP, diaphoresis = sweating), altered consciousness, increase creatinine kinase (CK)
- lead-pipe rigidity, fever, high CK
- high-potency antipsychotics
- rare, but potentially lethal
- onset: hours to 3 days (within 30 days)
how do we manage neuroleptic malignant syndrome (NMS)?
- IV Dantrolene 50mg TDS
- oral dopamine agonist (e.g. amantadine, bromocriptine), supportive measures
- switch to SGA, low dose, least potent
which drugs increases the risk of psychogenic polydipsia
- def: increase intake of water
- anticholinergics causes it
what can be the management of psychogenic polydipsia?
- fluid restriction, discontinue drugs w anticholinergic properties
which drugs increase the risk of temperature dysregulation?
- anticholinergics
what can be the management of temperature dysregulation
- hydration. appropriate clothing/shade
what is the hepatic SE of antipsychotics?
increase LFTs (usually benign), cholestatic jaundice
which drugs can cause increase LFTs?
- chlorpromazine, olan, quet > other SGAs
what is the management of increase LFT?
if jaundice develops, discontinue antipsychotics
what ophthalmologic SE can be caused by antipsychotics?
cornea/lens changes, pigmentary retinopathy
which drugs increase the risk of cornea/lens changes, pigmentary retinopathy?
Phenothiazines (chlorpromazine, thio), Quet
what is the management for the ophthalmologic SE?
if on Quet, eye exam q6 months
what dermatological SE can be caused by antipsychotics?
maculopapular rash, photosensitivity, pigmentation
which drugs increase the risk of the dermatological SE?
Phenothiazines (chlorpromazine)
what is the management of the dermatological SE?
protective clothing, sunscreens
- consider switch to other antipsychotics
IMPORTANT what is the hematological SE of using antipsychotics
- decrease WBC
- Agranulocytosis –> decrease absolute neutrophil count
which drug can cause the hematological SE?
- CLOZAPINE
what is the management for the hematological SE?
- discontinue antipsychotic if severe: WBC < 3x10^9/L or ANC <1.5x10^9/L
ANC = absolute neutrophil count
when do we monitor BMI in patients taking antipsychotics?
- if the concerned SE is weight gain
- weekly for 1st six weeks or every visit (at least monthly x 3 months for SGA) x 6 months
- q3 months when dose stabilised
when do we monitor waist circumference in patients taking antipsychotics?
- when the concerned SE is obesity
- every visit x 6 mths, then annually
when do we monitor for fasting blood sugar in patients taking antipsychotics?
- when the concerned SE is diabetes mellitus
- for low-risk patients: annually
- for high-risk patients: 4 mths after initiating new antipsychotic (or 3 months after initiating SGA), then annually
when do we monitor for lipid panel in patients taking antipsychotics?
- when concerned SE is hyperlipidemia
- low risk patients: q2-5 yrs
- high risk patient: (3 months after initiating SGA), q6mths
when do we monitor for plasma prolactin in patients taking antipsychotics?
- when concerned SE is hyperprolactinemia
- monitor at baseline
when do we monitor for blood pressure in patients taking antipsychotics?
- when concerned SE is increase or decrease BP
- monitor q3 months after initiating SGA, then annually
when do we do a EPSE exam for rigidity, tremors, akathisia, tardive dyskinesia in patients taking antipsychotics?
when EPSE is a concerned SE
- weekly for 1st 2 weeks after initiation new antipsychotic or until dose stabilised
- low risk patients: FGA q6mths, SGA q12mths
- high-risk patients: FGA q3mths, SGA q12mths
when do we monitor for WBC and ANC (absolute neutrophil count) in patients taking antipsychotics?
- when CLOZAPINE is taken and
leucopenia/agranulocytosis is a concerned SE - in SG: weekly for first 18 weeks, then monthly
when do we monitor for ECG in patients taking antipsychotics?
- when patient taking Ziprasidone and QTc prolongation is a concerned SE
- repeat ECG if symptoms of QTc prolongation (e.g. syncope)
most SGA need to monitor for _ mths
3mths for BMI, and lipid panel, then followed by q6 mths
3mths for fasting blood sugar, lipid, blood pressure, then annually
q12mths for EPSE
in pregnancy, which drugs are of concern?
- olanzapine, clozapine, to watch for gestational diabetes
what drugs are suitable in breastfeeding
- olanzapine or quetiapine
what drugs is not suitable in breastfeeding?
- clozapine should be continued and not breastfeed
which drug is preferred in renal impaired patients?
PO Aripiprazole
which drugs to avoid in renal impaired patients?
- avoid sulpride and amisulpride
which drugs are preferred in hepatic impaired patients
- sulpride and amisulpride
what drugs are to be avoided in elderly*
- avoid drugs with high a1-adrenergic blockade (orthostatic hypotension)
= chlorpromazine, clozapine - avoid drugs with anticholinergic SE (constipation, urinary retention, delirium)
= benztropine, diphenhydramine, benzhexol (aka trihexyphenidyl), other F/SGAs - avoid adverse interactions - go for simple regime
- avoid long T1/2 drugs
- start low go slow
what is the dosing for elderly?
- start low go slow
- simplify regime
what is the precaution for elderly with dementia?
FGA/SGAs reported to increase mortality and CVAs
what are the PD drug interactions that are of concern?
– increase CNS depression by combining 2 CNS depressants; increase risks of seizures by combining drugs that lower seizure thresholds
- additive effect = agonistic + agonistic effect
2 drugs affect same organ system but by different mechanisms:
- synergistic = potentiation
- antagonism: 2 drugs reduce each other’s effect
what drug-disease interaction is of concern
antipsychotics worsen Parkinson’s disease sx
Drugs with CNS depressant effects + antipsychotics causes
- Additive CNS effects
e. g. BZDs and Clozapine –> reduce RR and BP
drugs with CNS depressant effects?
- alcohol, opioids, other psychotropics
drugs with antimuscarinic, anti-H1, a1 blockade or dopamine blockade + antipsychotic
- additive adverse effect
dopamine-augmenting agents (e.g. levodopa, bromocriptine) + antipsychotic
mutual antagonism with antipsychotic
antihypertensives/trazodone + antipsychotics
increases hypotensive effects
CYP1A2 inducers (rifampicin, phenobarbitone, phenytoin, cigarette smoking) + antipsychotic
decreases phenothiazines (CPZ), Halo, Cloz, Olan, Zip
CYP 1A2 inhibitors (fluvoxamine, quinolones, macrolides (except azithromycin), isoniazid, ketoconazole) + antipsychotics
increases phenothiazines (CPZ), Halo, Cloz, Olan, Zip
carbamazepine + clozapine
agranulocytosis
what are the CYP1A2 inducers
rifampicin, phenobarbitone, phenytoin, cigarette smoking
what are the CYP1A2 inhibitors
fluvoxamine, quinolones, macrolides (except azithromycin), isoniazid, ketoconazole
what are the CYP2D6 inducers?
- rifampicin, phenobarbitone, phenytoin, carbamazepine
what happens when CYP2D6 inducers + antipsychotics
decreases phenothiazines (chlorpromazine), halo, risp, ari, Olan, Zuclopenthixol
what are the CYP2D6 inhibitors?
fluoxetine, paroxetine, duloxetine
what happens when CYP2D6 inhibitors + antipsyhotics
increases phenothiazines (chlorpromazine), halo, risp, ari, Olan, Zuclopenthixol
what are the CYP3A4 inducers?
- barbiturates, carbamazepine, phenytoin
what happens when CYP3A4 inducers + antipsychotics
decreases Quet, Zip, Ari, Risp
what are the CYP3A4 inhibitors
fluvoxamine, norfluoxetine, TCAs, imidazoles, isoniazid, macrolides
what happens when CYP3A4 inhibitors + antipsychotics
increases Quet, Zip, Ari, Risp
what happen when 5-HT augmenting agents are added with antipsychotics
may antagonise 5-HT2a receptor blockade –> decrease dopamine release and worsening EPSEs
how do we monitor for effectiveness of therapy?
Mental Status exam (MSE)
psychiatric rating scales
- 4-item positive sx rating scale (PSRS) and brief negative symptom assessment (BNSA)
- easy to administer, 15min
what do we monitor in terms of adverse effects?
- metabolic parameters: fasting plasma glucose, lipids, body weight, BP
- EPSE
- -> drug-induced pseudo parkinsonism: simpson-angus rating scales
- -> akathisia: Barnes akathisia scale
- -> tardive dyskinesia: AIMS, DISCUS
what is the time course of treatment response
- early improvements
- 1st week –> reduced agitation, aggression, hostility
- 2-4 weeks –> decrease paranoia, hallucinations - late improvements
- 6-12 weeks –> decrease delusions, negative sxs may improve
- 3-6 months –> cognitive sx may improve (with SGAs)
SUMMARY
what are the clinical features of schizophrenia
- positive sx, negative sx, functional impairment
- accurate diagnosis necessary to guide treatment and subsequent monitoring
schizophrenia aka thought disorder
SUMMARY
what is the MOA of the antipsychotics (aka thought organisers)
- FGA & SGA
- D2 antagonism (in mesolimbic dopamine tract) improves +ve sxs
- SGA only
- 5HT2A antagonism may improve mood sxs, and possibly also negative sxs
SUMMARY
what is the clinical differences between SGA and FGA?
for efficacy:
- SGA effective for BOTH positive sx and mood sx
- FGA effective mainly for positive sx
for toxicity:
- FGA: more ‘muscle SE’ = EPSE
- SGA more ‘metabolic SE’ (except aripiprazole, brexpiprazole, lurasidone, ziprasidone)
SUMMARY
which SGAs are more sedating, more weight gain?
the ‘ines’ = Clozapine, Olanzapine, Quetiapine
vs
‘ones’ or ‘piprazoles’= risperidone, lurasidone, ziprasidone, aripiprazole)
- less sedating, less weight gain
SUMMARY
what is the non-pharmacological management for schizophrenia?
supportive counselling, social skills therapies, rehab, vocational training
SUMMARY
what is the pharmacological treatment like for schizophrenia?
- 1st line: suitable non-clozapine antipsychotic (SGA or FGA) and titrate
- choose the antipsychotic formulation:
- -> Oral (immediate release, oral dispersible, oral soln, oral extended release)
–> intramuscular:
- IM rapid acting (e.g. IM Haloperidol or IM Olanzapine)
(for v agitated)
- IM long acting (e.g. Haloperidol decanoate)
SUMMARY
what is the duration for an adequate antipsychotic trial?
- at least 2-6 weeks at recommended therapeutic dosing range
- clozapine trial may require 3 mths
SUMMARY
what are the adjunctive treatments for schizophrenia?
- BZDs (for agitation)
- antidepressants (for depression)
SUMMARY
what is treatment resistant schizophrenia (TRS)
- not responsive to at least TWO adequate trials of antipsychotics, of which one is a SGA
- Clozapine is the drug of choice for TRS
- -> monitor baseline and periodic FBC (full blood count) with ANC (absolute neutrophil count) due to risk of agranulocytosis
SUMMARY
What is the acute stabilisation phase?
- goal: reduce agitation, aggression hostility; improve sleep
- if acutely agitated/aggressive:
1st: de-escalate
2nd: consider oral antipsychotic +/- BZD
3rd: if refuse or not possible to administer oral med –> consider FAST-acting IM alternative w monitoring: - -> IM haloperidol 5mg w ECG + IM Lorazepam 2mg
- monitor for treatment-emergent adverse effects
e. g. dystonia, pseudo-parkinsonian SE - treat accordingly (oral or IM benztropine 2mg) - monitor vitals (BP/HR/RR/oximetry, temp, pain, hydration status)
SUMMARY
what is the stabilisation and maintenance phase
- goal: minmise/prevent relapse, maintain baseline functioning
- monitor and manage adverse effects
- if poor adherence to oral med, or if pt prefers IM, consider:
- -> IM long-acting antipsychotic: IM Haloperidol Decanoate
- -> community psychiatric nurse referral
SUMMARY
how do we manage dystonia, tremors/rigidity EPSE?
- anticholinergics (benzotropine/ diphenhydramine/ trihexyphenidyl (benzhexol))
or - switch to lower-potency antipsychotics (e.g. quetiapine, sulpride)
SUMMARY
how do we manage akathisia EPSE?
- clonazepam and/or propranolol, or
- switch to a SGA or lower-potency antipsychotic
SUMMARY
how do we manage tardive dyskinesia EPSE?
- can be irreversible if detected late in advanced stages
- discontinue any anticholinergics
- switch to low potency SGA
- treat with valbenazine
- clonazepam PRN
SUMMARY
how do we manage the metabolic SE
metabolic SE; weight gain, elevated fasting lipids, glucose profiles
- maintain on current antipsychotics to prevent relapse but treat the emergent diabetes, dyslipidemia with lifestyle and med (e.g. metformin for DM, statins for hyperlipidemia) or
- switch to aripiprazole, brexpiprazole, lurasidone, ziprasidone, haloperidol
SUMMARY
how do we manage the daytime sedation SE?
- administer dose in early evening (e.g. 7pm) for sedation to wear off
- consolidate to once-nightly dosing whenever possible (EXCEPT for clozapine or quetiapine due to risk of seizures and severe hypotension)
SUMMARY
how do we manage dizziness (orthostatic hypotension) SE
- rise up slowly from a lying/sitting position
