IC11 Schizophrenia Flashcards
Dx a/w psychotic sx
- Organic disorders: iatrogenic causes/ drug induced, alcohol/substance misuse
- Affective disorders: mania, depression, post-partum psychosis
- Schizophrenia
Drugs that can cause psychosis
alcohol, benzodiazepine, barbiturates, antidepressants, corticosteroids, CNS stimulants (amphetamines), beta blockers (propanolol), dopamine agonist (levodopa, bromocriptine)
criteria for schizophrenia
- ≥2 sx for 1mth
1. delusions
2. hallucinations
3. disorganised speech
4. grossly disorganised, catatonic behaviour
5. negative sx - impaired daily function
- duration: ≥6mths
- exclude medical disorder/ substance use
Non-pharm
supportive counselling, social skill therapy, vocational training (employment, rehab), CBT, family support, ECT, psychosocial rehab
Acute stabilisation tx goals
minimise threat to self and others, minimise acute symptoms, decrease agitation, improve slp
Stabilisation tx goals
prevent relapse, promote medical adherence (usually lifelong), optimise dose
Stable/maintenance tx goals
improve functioning and QOL
Indication for antipsychotics
schizophrenia, adjunct with antidepressants for MDD, bipolar disorders
Purpose of antipsychotic
In short term, used to calm disturbed pt but does not induce coma (unlike benzodiazepine and barbiturates)
- relief sx of psychosis
- prevent relapse
When will relapse occur after stopping meds
Relapse often delayed for several weeks after cessation
Methods to overcome poor tx adherence
IM long acting injection, community psychiatric nurse, pt and family/caregiver education
Effect of blocking dopamine in mesolimbic tract
Mesolimbic tract (D2): dopamine blockade → reduction in positive sx in schizophrenia
Effect of blocking dopamine in mesocortical tract
dopamine blockade/ hypofunction → increase negative sx
Effect of blocking dopamine in nigrostriatal tract
Nigrostriatal tract (D1/D2): dopamine blockade → Extrapyramidal SE (EPSE/ Parkinson’s like movement disorders) — eg resting tremors, cork-wheel rigidity, shuffling gait, hunch back, stiff posture
Effect of blocking dopamine in tuberoinfundibular tract
Tuberoinfundibular tract (D2/D3): dopamine blockade → increase prolactin (breast swelling, lactation, gynaecomastia)
D2 antagonism cause…
Antagonism: improve +’ve sx, EPSE, hyperprolactinemia
5HT1A agonism cause…
Agonism: anxiolytic (calming)
5HT2A antagonism cause…
Antagonism: improve -’ve sx
5HT2C antagonism cause…
Antagonism: weight gain
H1 antagonism cause…
sedation, weight gain
alpha-1 antagonism cause…
postural hypotension
M1 antagonism cause
blurred vision, dry mouth, constipation
PK: Tmax and T1/2 of antipsychotics
Tmax: 1-3hrs
T1/2: long (can do OD) except clozapine, quetiapine (BD dosing)
Eg of FGA
chlorpromazine, haloperidol
Eg of SGA
clozapine, olanzapine, quetiapine, risperidone, aripiprazole, brexpiprazole
Eg of IM antipsychotics
- rapid acting (haloperidol q4wks, olanzapine q4wks, risperidone q2wks)
- paliperidone (q3mths)
- long acting (haloperidol decanoate)
Tx plan for schizophrenia
- Step 1 and 2: Use single FGA/SGA (except clozapine) for 2-6 weeks
- Step 3: Use clozapine
Adequate trial duration of antipsychotic before determining ineffective
at least 2-6 weeks at optimal therapeutic doses
monitoring for clozapine
must do FBC every WEEK for first 18weeks, then monthly/28 days
when can clozapine be used?
failed ≥2 adequate trials of different antipsychotics (at least one must be SGA)
Precaution to antipsychotic use
- CVD — CI in QTc prolongation
- PD — EPSE worsened by antipsychotics
- Prostatic hypertrophy — urinary retention worsened by antimuscarinic/anticholinergic (ARU is a medical emergency)
- Angle-closure glaucoma
- Severe respiratory disease
- Blood dyscrasia — esp for clozapine (agranulocytosis)
- Elderly with dementia — increased risk of mortality and stroke
Acute agitation (psychiatric emergency) tx if cooperative
- PO lorazepam
- PO antipsychotic (if pt has agitation + psychosis → give antipsychotics): haloperidol, olanzapine, quetiapine, risperidone
Acute agitation (psychiatric emergency) tx if NOT cooperative
(use fast acting IM injection)
- IM lorazepam (benzodiazepine)
- IM olanzapine
- IM haloperidol
- IM promethazine (sedating antihistamine)
- IM haloperidol + promethazine/ lorazepam
Catatonia (abnormal movements) tx
PO/IM lorazepam (benzodiazepines)
FGA SE
EPSE, hyperprolactinemia
Clozapine, Olanzapine, Quetiapine SE
no EPSE, more sedating and weight gain/DM/lipid
Risperidone SE
less EPSE, less metabolic
Aripiprazole, Brexpiprazole SE
no EPSE, no metabolic
4 sx of EPSE
- dystonia
- pseudo-parkinsonism
- akathisia
- tardive dyskinesia
mx of dystonia
- IM benztropine/ diphenhydramine (anticholinergic - can cause constipation)
- decrease dose, switch to SGA
mx of pseudo-parkinsonism
- PO anticholinergic PRN (benztropine, benzhexol)
- decrease dose, switch to SGA
mx of akathisia
- decrease dose, switch to SGA
- low dose clonazepam/ lorazepam PRN
(NO anticholinergic)
mx of tardive dyskinesia
- discontinue any anticholinergic
- decrease dose, switch to SGA
- tx: valbenazine
- clonazepam/ lorazepam PRN
mx of hyperprolactinemia
- decrease FGA dose
- switch to aripiprazole/ brexpiprazole
mx of metabolic SE
- Lifestyle modification: diet, exercise
- Treat DM → metformin
- Treat hyperlipidemia → statins
- switch to aripiprazole, brexpiprazole, cariprazine, lurasidone
mx of OH
get up slowly
mx of QTc prolongation
monitoring
mx of daytime sedation
take meds at evening
sx of neuroleptic malignant syndrome (NMS)
fever, increase CK, lead pipe rigidity, sweating, confusion
mx of NMS
AnE
- IV dantrolene/ PO dopamine agonist (bromocriptine)
- switch to SGA
causes of NMS
- succinylcholine (neuro-muscular blocker) used in operating theatre
- potent IM antipsychotics
- sudden withdrawal of levodopa
mx of agranulocytosis
AnE, if severe discontinue
Monitoring parameters
BMI, fasting blood sugar, lipid panel, blood pressure, EPSE exam, WBC and ANC count (for clozapine)
drugs to avoid in elderly
- alpha-1 antagonism (decrease BP, postural hypotension)
- anticholinergic/ antimuscarinic (constipation, urinary retention) effects
Drug-disease interactions
antipsychotics worsen Parkinson’s Disease
Drug-drug interactions
- CNS depressant effects
- Drugs with M1, a1, H1 blockade -> additive AE
- Dopamine agonists (eg levodopa, bromocriptine)
- Antihypertensives -> increase hypotension
- Carbamazepine -> agranulocytosis with clozapine
Monitoring for effectiveness of therapy
MSE (mental status exam)
Monitoring for adverse effects
- Metabolic parameters: fasting plasma glucose, lipids, body weight, BP
- EPSE: pseudo-parkinsonism, akathisia, tardive dyskinesia
Tx response (early improvement)
- 1st week: decrease agitation
- 2-4 weeks: decrease paranoia, hallucinations
Tx response (late improvement)
decrease delusions
