schizophrenia clinical Flashcards
what are the positive symptoms of schizophrenia
abnormal behaviours
hallucinations
delusions
though insertion/withdrawal/echo/broadcasting
disorganised speech
disorganised or catatonic behaviour
what are the negative symptoms of schizophrenia
absence of normal behaviours
flattened mood
no motivation
apathy
alogia
anhedonia
social isolation
slow movements
self-neglect
how is 1CD10 used to diagnose schizophrenia
at least one of the following for 1m
- Thought insertion/echo/broadcasting/withdrawal
- Delusions of control
- Hallucinatory voices
- Culturally inappropriate persistent delusions
OR at least two of the following
- Persistent hallucinations of any modality occurring every day for weeks/months
- Breaks of interpolations in train of thought resulting in incoherence
- Catatonic behaviour – excitement, posturing, mutism, stupor
- Negative symptoms such as apathy, poverty of speech
- Significant change in loss of interest, aimlessness, idleness, self-absorption and social withdrawal
how does DSM5 diagnose schizophrenia
Two or more of the following (with one of 1/2/3), each present for a significant amount of time over a 1m period
1. Delusions
2. Hallucinations
3. Disorganised speech
4. Grossly disorganised or catatonic behaviour
5. Negative symptoms
Social/occupational dysfunction
- For a significant amount of time since onset
- Level of functioning in one or more major areas is remarkedly below the persons level prior to onset
Continuous signs for 6m that must include 1m of symptoms 1/2/3
Exclusions
- Schizoaffective disorder or bipolar disorder ruled out
- Presentation is not attributable to the physiological effects of a substance (e.g. drug of abuse, medication) or other medical condition.
what are the differential diagnosis for schizophrenia
substance misuse
physical illness
severe mood disorder
PTSD
OCD
personality disorder
ASD/communication disorder
dementia
how do 1st gen antipsychotics work
D2 antagonists with H1, muscarinic and alpha 1 activity
what are some 1st gen antipsychotics
Phenothiazine
- Chlorpromazine
- Pericyazine
- Prochlorperazine
Butyrophenones
- Haloperidol
Thioxanthenes
- Flupentixol
- Zuclopenthixol
Substituted benzamides
- Sulpiride
- Amisulpride
what are the most common s/e witth 1st gen antipsychotics
neurological s/e
EPSEs
anticholinergic
cardiac
hyperprolactinaemia
sexual dysfunction
how do second gen antipsychotics work
5HT2 antagonists, fast D2 dissociation and 5HT1A agonism
what are some examples of 2nd gen antipsychotics
- Clozapine
- Olanzapine
- Risperidone
- Quetiapine
- Aripiprazole
- Lurasidone
what are the main side effects of 2nd gen antipsychotics
metabolic syndrome
anticholinergic
hyperprolactinemia
sexual dysfunction
how are antipsychotic depot/LAI used
1st gen need IM test - ESPEs and oily carrier
2nd gen need oral meds first but no IM
which antipsychotics can be given as depo
haloperidol - 4 weekly
flupentixol
zuclopenthixol
aripiprazole - oral/IM loading dose required
risperidone - 2/3 week delay, oral meds
olanzapine - post inj syndrome, monitor for 3 hrs
what are the advantages to using depot injection antipsychotics
- Continuous coverage
- Better for patients
- Immediate notification of non-adherence
- Remains in system 1-2 weeks after missed dose
- Avoids first pass
- Reduced relapse rates
- Smoother release profile
what are the disadvantages of using depot antipsychotics
- Painful, can cause site reactions
- Oral to IM conversion not always straightforward
- Stigma
- Dose titrations harder
- Adverse effects can persist until drug is cleared
what are the general monitoring requirements for antipsychotics
QTc - ECG
BP
pulse
plasma glucose
lipid panel
weight/BMI
what is rapid tranquilisation and what medicines are used for it
use of IM meds when oral is not available or suitable and urgent sedation is needed
IM lorazepam or haloperidol with promethazine
what are the monitoring requirements for rapid tranq
pulse
BP
RR
temp
hydration
consciousness
what is used to treat treatment resistant schizophrenia
clozapine - weak D2R antagonist with action at 5HTAR, anticholinergic, antihistaminergic and alpha 1 adrenergic properties
when would a patient be considered for clozapine treatment
no response to 2 antipsychotics - one being 2nd gen- after treatment for at least 4/6 weeks
clozapine monitoring requirements
Register with approved clozapine blood monitoring service (weekly for 18, 2 weekly until 1 year and then monthly)
what do clozapine blood test results of WBC >3500/mm3 and ANC >2000/mm3 suggest
routine tests - continue as normal
what do clozapine blood test results of WBC between 3500 and 3000/mm3 or the ANC between 2000 and 1500/mm3 suggest
repeat test twice weekly until improvement or decline - continue treatment
what do clozapine test results of WBC below 3000/mm3 and/or absolute neutrophils below 1500/mm3 suggest
immediate cessation of treatment - blood tests daily until resolution - no further prescribing unless error occurred or prescriber takes accountability
what are the symptoms of antipsychotic withdrawal
N&V
sweating
muscle pains
insomnia
restlessness
anxiety
seizures
EPSEs
- akathisia
- dystonia
- dyskinesias
may have cholinergic rebound
what EPSEs are associated with antipsychotics
dystonia - switch/give procyclidine
parkinsonisms- dose reduction, procyclidine or switch to 2nd gen
akathisia- dose reduction, benzo course or switch
tardive dyskinesia - stop anticholinergics, reduce dose or switch to clozapine or quetiapine
what is metabolic syndrome and which antipsychotics cause it
- Weight gain, increased insulin and glucose and dyslipidaemia - 2nd gens (olanzapine/clozapine)
what are the monitoring parameters for metabolic syndrome in antipsychotic use
waist circum
fasting BM
HbA1c
lipid panel
- before, a2 wks, annually (3m for clozapine and olanzapine)
what are the symptoms and management of hyperprolactinaemia associated with antipsychotics
can be asymptomatic
- sexual dysfunction, menstrual issues, breast growth, loss of bone mineral density, increased breast cancer risk
manage by reduce dose, switch to prolactin sparing (aripiprazole) or add low dose aripiprazole (off license)
how is sexual dysfunction as a result of antipsychotics managed
- Monitor prolactin
- Consider spontaneous resolution
- Adjust dose
- Switch
- Add 3-6mg aripiprazole (unlicensed)
- Specialist – sildenafil or priapism
how is sedation as a result of antipsychotics managed
- Review all meds
- Use minimum effective dose
- Counsel
- Diminish with longer use
- Trial dose reduction
- Switch
- Prescribe at night
- Avoid psychostimulants – can worsen
what are the central anticholinergic effects that can be seen with 1st gen antipsychotics and clozapine
- Cognitive impairment
- Delirium
- Hyperthermia
- Confusion
what are the peripheral anticholinergic effects that can be seen with 1st gen antipsychotics and clozapine
- Dry mouth
- Constipation
- Blurred vision
- Glaucoma
- Urinary retention
how are anticholinergic s/e of antipsychotics managed
- Identify patients who have pre-existing conditions (narrow angle glaucoma etc)
- Review other meds
- Low and slow
- Trial dose reduction
- Switch
what are the cardiac s/e associated with antipsychotic use
- Orthostatic/postural hypotension (alpha1 antagonists)
- Reflex tachycardia (alpha1 antagonists and anticholinergic)
- Ventricular tachycardia
- Torsades de pointes
- Delayed cardiac repolarisation
- Myocarditis
- Myocardial infarction
- Cardiomyopathy
what cardiac monitoring is required for antipsychotics
- BP and pulse baseline
- ECG
- Repeat at 12 weeks and then annually
how are cardio side effects of antipsychotics managed
- Education
- Gradual dose titration
- Dose reduction
- Switching
- Add in appropriate medication to reduce HR
- Review concurrent medication that may exacerbate effects
- If myocarditis is suspected - STOP and refer as appropriate
what are the cardiac side effects of clozapine
thromboembolism
myocarditis - 6-8wks of treatment - hypotension, tachycardia, fever, flu, fatigue
cardiomyopathy - 9m of treatment
what are the haematological side effects of clozapine
Agranulocytosis (0.4%)
- Managed by enrolment onto clozapine monitoring system
- WBC & platelets at baseline and weekly for 18, 2 weekly until 1yr – monthly
what are the constipation side effects of clozapine
dose reduction
- Anticholinergic, antihistaminergic and 5HT3 antagonism
stimulants/softeners - no bulk
what are the hypersalivation side effects of clozapine
dose related- may improve over time
- reduce or switch
- antimuscarinics - can worsen other S/E
lifestyle
what is Neuroleptic malignant syndrome
Acute disorder of thermoregulation and neuromotor control
what are the symptoms of neuroleptic malignant syndrome
- Fever
- Diaphoresis
- Rigidity
- Confusion
- Fluctuating consciousness and BP
- Tachycardia
- Elevated CK
- Altered LFTs
- Leucocytosis
what are the risk factors for neuroleptic malignant syndrome
- High potency 1st gen
- Recent/rapid dose increase/reduction
- Abrupt anticholinergic withdrawal
- Antipsychotic poly pharmacy
- Male
- Young
- Dehydration
- Psychosis
- Brain/Parkinson’s disease
- Alcoholism
- Hyperthyroidism
how are antipsychotics restarted after neuroleptic malignant syndrome
- Allow at least 5 days before restarting
- Low and slow
- Consider an antipsychotic that is structurally unrelated to the causative agent or one with lower dopamine affinity (quetiapine, clozapine or aripiprazole)
- Avoid Depot or LAI
which antipsychotics cause QT prolongation and what do they interact with
haloperidol/quetiapine
- (es)citalopram
- Eryth/clarithromycin
- Tamoxifen
- Sotalol
- Amiodarone
- Venlafaxine
which antipsychotics cause neutropenia/agranulocytosis and what do they interact with
clozapine
- Carbamazepine
- Cytotoxics
- Chloramphenicol
which antipsychotics cause sedation and what do they interact with
Chlorpromazine, Clozapine, Olanzapine, Quetiapine ,Pericyazine, Zuclopenthixol
- Alcohol
- Benzos
- Mirtazapine
- Antihistamines
- Opiates
- Trazadone
- TCAs
which antipsychotics cause anticholinergic s/e
- Chlorpromazine
- Clozapine
- Zuclopenthixol
which antipsychotics cause low BP and what do they interact with
chlorpromazine, clozapine, risperidone
- antihypertensives
- TCAs
- alcohol
which antipsychotics cause seizures and what do they interact with
clozapine, chlorpromazine
- TCAs
- sudden benzo withdrawal
which metabolic changes cause sedation and what do they interact with
chlorpromazine, clozapine, olanzapine
- lithium
- mirtazapine
- TCAs
- valproate
which antipsychotics are metabolised by CYP
- Clozapine
- Olanzapine
- Aripiprazole
- Chlorpromazine
- Haloperidol
- Risperidone
- Zuclopenthixol
- Quetiapine
what are some CYP inhibitors
- Caffeine
- Cimetidine
- Ciprofloxacin
- Amiodarone
- Duloxetine
- Fluoxetine
- Paroxetine
- Sertraline
- Diltiazem
- Clarith/erythromycin
- Verapamil
what are some CYP inducers
- Phenytoin
- Barbiturates
- Tobacco smoke
- Rifampicin
- Carbamazepine
what effect does tobacco smoke have on antipsychotics
reduces plasma clozapine levels by 50%
reduces olanzapine levels by 50%
what effect does caffeine have on antipsychotics
- Increase in clozapine levels by up to 60%
