Schizophrenia Flashcards
Schizophrenia sns
A) Two or more of the following, each persisting for a significant portion of at least a 1-month period:
(1) delusions
(2) hallucinations
(3) disorganized speech
(4) grossly disorganized or catatonic behavior
(5) negative symptoms
(e. g. Affective flattening, Alogia, Anhedonia, Avolition)
B) Social/occupational dysfunction
one or more major areas of functioning such as work
C)Continuous signs of the disorder for at least 6 months.
D. Schizoaffective or mood disorder has been EXCLUDED.
E. Disorder is NOT due to a medical disorder or substance use.
F. If a history of a pervasive developmental disorder is present, there must be symptoms of hallucinations or delusions present for at least 1 month.
Non-Pharmacological Treatment
Individual Cognitive Behavioural Therapy (CBT)
– Used in conjunction with medications and family Intervention
- First Episode Psychosis: Assess for PTSD
Electroconvulsive Therapy (ECT) – Reserved for treatment-resistant Schizophrenia
Repetitive Transcranial Magnetic Stimulation (rTMS) – Effective for reducing auditory hallucinations in Schizophrenia
Psychosocial rehabilitation programs:
- improving patient’s adaptive functioning
Electroconvulsive Therapy (ECT) – Reserved for treatment-resistant Schizophrenia
Electroconvulsive Therapy (ECT) – Reserved for treatment-resistant Schizophrenia
Effective for reducing auditory hallucinations in Schizophrenia
Repetitive Transcranial Magnetic Stimulation (rTMS) – Effective for reducing auditory hallucinations in Schizophrenia
Repetitive Transcranial Magnetic Stimulation (rTMS) –
Repetitive Transcranial Magnetic Stimulation (rTMS) – Effective for reducing auditory hallucinations in Schizophrenia
Pharmacological Treatment:
Establishing Therapeutic Goals
- Acute Stabilization
a. Minimize threat to self and others
b. Minimize acute symptoms
c. Improve role functioning
d. Identify appropriate psychosocial interventions
e. Collaborate with family and caregivers; Support for Carers - Stabilization
a. Minimize/prevent relapse
b. Promote medication adherence
c. Optimize dose vs. adverse effects - Stable/maintenance phase
a. Improve functioning & quality of life
b. Maintain baseline functioning
c. Optimize dose vs. Adverse effects
d. Monitor for prodromal Sx of Relapse
e. Monitor for Adverse effects (e.g. Tardive Dyskinesia)
Pharmacological Treatment
Class
Function
Duration
when will Relapse
Antipsychotic Medications”
– Also known as “Neuroleptics”
• Generally tranquilize without impairing consciousness and without causing paradoxical excitement.
In the short term, they are used to calm disturbed patients whatever the underlying psychopathology which may be. • E.g. schizophrenia, mania, toxic delirium, or agitated depression.
Antipsychotics relieve symptoms of psychosis such as thought disorder, hallucinations and delusions, and prevent relapse.
- Usually less effective in apathetic withdrawn patients.
- Patients with acute symptoms of schizophrenia generally respond better than those with chronic
symptoms.
Long-term treatment often necessary after the first episode of psychosis and prevent illness from becoming chronic.
may relapse if treatment is withdrawn inappropriately.
Relapse is often delayed for several weeks after cessation of treatment.
- Adipose tissues act as depot reservoir after chronic regular usage of antipsychotics.
– The antipsychotic (stored in fat cells) then diffuses back into blood stream after treatment cessation, until depletion
Methods to overcome poor treatment adherence
Methods to overcome poor treatment adherence
• Community Psychiatric Nurse
• IM long-acting injections
• Patient and Family (Caregiver) Education
Mechanism of Action - Antipsychotics
The central dopamine systems is composed of the following 4 tracts:
(1) Mesolimbic Tract: Blockade of the dopamine receptors in this tract is probably the common mechanism of action for all antipsychotics, because overactivity in this region is responsible for positive symptoms of Schizophrenia.
Blockade of the remaining 3 dopamine tracts causes adverse effects.
(2) Mesocortical (MC) Tract: This tract is responsible for higher-order thinking and executive functions. Dopamine blockade or hypofunction in this region results in negative symptoms.
(3) Nigrostriatal (NS) Tract: This tract modulates body movement. Antipsychotic-induced dopamine blockade in this region causes Extrapyramidal Side Effects (EPSE).
(4) Tuberoinfundibular (TI) Tract: Dopamine blockade in this region of the anterior pituitary leads to hyperprolactinemia.
D2 antagonism clinical implication
D2 Antagonism:
improve (+)ve Sx
causes EPSE, Hyperprolactinaemia
5-HT2A Antagonism:
clinical implication
5-HT2A Antagonism:
Antidepressant effects?
improve (-)ve Sx?
D2 receptor blockage %
60% = antipsychotic 70% = prolactin threshold 80% = EPS threshold
Algorithm for Schizophrenia
Use a single FGA or SGA (except Clozapine) –>
INADEQUATE OR NO RESPONSE (~4-6 weeks) –>
Use another single FGA or SGA (except Clozapine) not previously tried –>
INADEQUATE OR NO RESPONSE (~4-6 weeks) –>
Clozapine
–> Clozapine + Augmenting Agent (FGA or SGA or ECT)
OR
Clozapine
–> Refusal or Intolerable side effects –>
Combination Therapy e.g. Antipsychotic combinations (either FGA+FGA, or FGA+SGA), Antipsychotic + either ECT or other agent (e.g. mood stabilizer)
Algorithm for Schizophrenia – Important Footnotes
- Medication selection is INDIVIDUALISE for a patient, based on physician’s assessment of clinical circumstances, past response/failures on antipsychotics, patient needs, efficacy and side effect profiles of the therapy.
- Patients require COMPLIANCE to an adequate trial of antipsychotic (excluding Clozapine) of at LEAST 4-6 weeks at optimal THERAPEUTIC doses (300 – 1000mg/day of Chlorpromazine equivalence) before being CONSIDERED as “non-responders” to the medication (Clozapine requires more time, up to 3 months). An adequate augmentation trial of up to 8-10 weeks is required if another antipsychotic is added to Clozapine.
- Manage any intolerable ADRs accordingly or switch to more suitable alternatives
- Consider a DEPOT/long-acting injectable antipsychotic if inadequately compliant,
- such as IM Risperidone microspheres, IM Paliperidone prolonged release suspension, IM Haloperidol decanoate or IM Fluphenazine decanoate, IM Flupenthixol Decanoate, IM Pipothiazine Palmitate. - Consider Clozapine in those who are Treatment-Resistant, i.e. those had failed 2 adequate trials of different antipsychotics (at least 1 should be a SGA).
Routine hematological monitoring is required for patients on Clozapine. A treatment refractory evaluation should be performed to reexamine diagnosis, substance abuse, medication adherence, and psychosocial stressors.
Cognitive Behavioral Therapy or Psychosocial augmentation should be considered.
DEPOT/long-acting injectable antipsychotic
- such as IM Risperidone microspheres, IM Paliperidone prolonged release suspension, IM Haloperidol decanoate IM Fluphenazine decanoate, IM Flupenthixol Decanoate, IM Pipothiazine Palmitate.
Precautions to Antipsychotic use
– Cardiovascular disease
• QTc prolongation (contraindicated)
• ECG may be required if physical exam identifies cardiovascular risk factors, or if there is personal history of cardiovascular disease, or if patient is being admitted as inpatient.
– Parkinson’s disease
• May be exacerbated by antipsychotics
– Epilepsy And conditions predisposing to epilepsy
– Depression – Myasthenia gravis – Prostatic hypertrophy – Angle-closure glaucoma – Severe respiratory disease – History of jaundice
– Blood dyscrasias, • especially for Clozapine
– Elderly with Dementia • Increased risks for mortality and stroke.
Adjunctive Treatments
Acute Agitation (Psychiatric Emergency)
If patient cooperative: • Consider Oral Medication (A) p.o. Lorazepam 1 – 2mg, or (B) p.o Haloperidol* (tab, solution) 2 – 5mg or (C) (A)+(B), or
(D) p.o. Risperidone (tab, orodispersible, solution) 1–2mg, or
(E) (A)+(D), or
(F) p.o. Olanzapine (tab, orodispersible) 5 – 10mg, or
(G) p.o. Quetiapine 50-100mg (tab)
If patient uncooperative and remains agitated/ aggressive:
• Consider fast-acting IM injection
(a) IM Lorazepam 1 – 2mg, or
(b) IM Haloperidol* 2.5 – 10mg (pre-treatment ECG recommended but can be impossible to do), or
(c) (a)+(b), or
(d) IM Promethazine 25-50mg, or
(e) (b)+d).
Note *Consider use of anticholinergic where appropriate
• IM Aripiprazole, IM Ziprasidone, IM Olanzapine or S/L Asenapine may be considered if available
Catatonia
– Benzodiazepines • po/IM Lorazepam
Management of Side Effects
EPSE Dystonia ~10%
EPSE Dystonia ~10%
- Muscle spasms, e.g. oculogyric crisis, torticollis
- Onset: within minutes (if IM/IV) or hrs (if p.o.)
Risk
High potency antipsychotics: (eg haloperidol), neuroleptic-naïve patients, young
management: IM anticholinergic (benztropine, diphenhydramine)
management of ADR
EPSE: Pseudo-parkinsonism ~20%
EPSE: Pseudo-parkinsonism ~20%
- Tremors, rigidity, bradykinesia, bradyphrenia, salivation
- Onset: days or weeks
Risk
- Elderly females, those with previous neurological damage (e.g. head injury, stroke)
Management
- Decrease antipsychotic dose, or switch to SGA
- Anticholinergics PRN, e.g benzhexol (aka trihexyphenidyl), benztropine.
EPSE: Akathisia ~25%
ADR MANAGEMENT
EPSE: Akathisia ~25%
- Restlessness
- Onset: hrs to weeks
Risk
- High-potency antipsychotics> Risp> Olan> Quet/Cloz
Management
- DECREASE antipsychotic dose, or switch to SGA
- Propranolol 20mg TDS (max 160mg/day)
- Clonazepam (low dose) PRN
- Anticholinergics generally unhelpful
EPSE: Tardive dyskinesia ~15-20%
management of SE
EPSE: Tardive dyskinesia ~15-20%
- Orofacial movements (lip chewing, tongue protrusion), choreiform hand movements pelvic thrusting.
- Onset: months/years to develop, 50% irreversible.
RISK
- FGA > SGA
- Those who develop acute EPSEs when initiated on FGA
- 5% of patients per year of antipsychotic exposure
- Worsen with anticholinergic drugs
Management
- Discontinue any anticholinergics
- DECREASE antipsychotic dose, or switch to SGA (Clozapine most effective)
- Valbenzine 40-80mg/day
- Tetrabenazine 25 – 200mg/day
- Clonazepam or diazepam PRN
- ? Vitamin E: 400 – 1600IU/day.
Hyperprolactinaemia management
Hyperprolactinaemia
- Galactorrhea
- Amenorrhoea
- DECREASE libido
- Gynecomastia (males)
RISK
- FGAs, Pali > = Risp >other SGAs
Management
- DECREASE FGA dose
- Dopamine agonist (e.g. amantadine, bromocriptine)
- Switch to Aripiprazole
management Metabolic SE
Metabolic
-Weight gain (of >7% from baseline), Diabetes, increase
Lipids
RISK
- High: Olan, Cloz
- Moderate: CPZ, Quet, Risp
- Low: Ari, Zip, Lura, Halo
Management
- Lifestyle modification: diet, exercise
- Treat diabetes (e.g. with metformin), hyperlipidaemia
- Switch to lower risk agents
ADR of antipsychotics
Dystonia
Pseudo-parkinsonism
Akathisia
Tardive dyskinesia
Hyperprolactinaemia
Metabolic
CVS = OH, QT
CNS = sedation, seizure, neuroeptic malignant syndrome (NMS)
Increase LFT
Retinopathy Rash pigmentation photosensitive agranulocytosis (clozapine)
Orthostatic hypotesion
management
risk
CPZ > Cloz > Risp
management: switch to lower risk agent eg
FGA : flupenthixol, sulpiride
SGA: Aripiprazole, olanzapine
QT prolong
risk and management
Thio > CPZ
management, switch to low risk agent
eg olan, ris
sedation
risk and management
CPZ, cloz > Quet
switch to lower risk agent
eg aripri
seizure
risk and management
cloz, cpz > other sga
switch to high potency agent eg: halo
NMS
risk and management
risk = high potency AP
management = IV dantrolene/oral dopamine agonist / supportive measure
switch to SGA
monitoring of SE
BMI
BMI = weekly for 1st 6 weeks or q visit x 6mth
(monthly x 3 months for SGA) x 6mth
q3mth when stabilise
monitoring SE FBG
3 months after initiating SGA then annually
WBC and ANC monitoring
weekly for 1st 18 weeks then monthly.
Monitoring of side effect
BMI waist circumference FBG lipid panel plasma prolactin BP EPSE exam
WBC and ANC (clozapine)
ECG (ziprasidone)
Pregnancy give ________
haloperidol
clozapine
Breast feed give ________
Sulpiride
olanzapine
Renal impairement give )___________
haloperidol
olanzapine
liver impairement give _______________
haloperidol
sulpiride/amisulpride
elderly: note
avoid drug with high propensity for A1 blockage or Anticholinergic SE
eg: ziprasidone, amisulpride, sulpride
start low go slow
Benzodiazapines + Clozapine: DROP RR, DROP BP
Benzodiazapines + Clozapine: DROP RR, DROP BP
Antihypertensives, Trazodone + antipsy
worsen hypotension
Carbamazepine + Clozapine
Agranulocytosis
CYP inducer VS CYP inhibitor
inducer decrease concentration of antipsy
inhibitor increase concentration of antipsy
influcence by 1A2
Phenothiazines, Halo, Cloz, Olan, Zi
influence by 2D6
Phenothiazines, Halo, Risp, Ari, Olan, Zuclopenthi
influence by 3A4
Quet, Zip, Ari, Risp
Time course of treatment response
Time course of treatment response
– Early improvements
• 1st week – decrease agitation, aggression, hostility
• 2-4 weeks – decrease paranoia, hallucinations, bizarre behaviours, – improved organization in thinking
Late improvements
• 6-12 weeks – decrease delusions, Negative Sxs may improve
• 3-6 months – Cognitive Sxs may improve (SGAs)
CYP1A2 inducer
Rifampicin
Phenobarbitone
Phenytoin
Cigarette smoking
CYP1A2 inhibitor
Fluoxamine Quinolone Macrolide Isoniazid Ketoconazole
CYP2D6 inducer
Rifampicin
Phenobarbitone
Phenytoin
Carbamazepine
CYP2D6 inhibitor
Fluoxetine
Paroxetine
Duloxetine
CYP3A4 inducer
Barbiturates
Carbamazepine
Phenytoin
CYP3A4 inhibitor
Fluvoxamine Norfluoxetine TCA Imidazole Isoniazid Macrolide
