Schizophrenia Flashcards
Structure of chlorpromazine
phenothiazine
Structure of haloperidol
butyrophenone
Structure of trifluoperazine
piperazine
Structure of thloridazine
piperidine
Structure of flupenthixol
thioxanthene
Structure of sulpride
benzamide
Structure of olanzapine
thienbenzodiazepine
Structure of clozapine
dibenzodiazepine
Structure of quetiapine
dibenzothiazine
Subtle differences in MOA of sulpride/amisulpride, risperidone, olanzapine/quetiapine, ziprasidone, aripiprazole
Sulpride/Amisulpride- presynaptic D4 at lower doses, d2 blockade at higher doses
Olanz/Queti- D2/5HT2 antagonists + H1 (sedative)
Risperidon- D2/5HT2 antagonists + a1 blockade (first dose hypotension)
Ziprasidone- 5HT/D2 antagonist, agonist at 5HT21A w/ monoamine reuptake inhibition
Aripiprazole- partial agonist D2, 5HT2 antagonist, partial agonist 5HT1A
What are the main principles of managing first episode psychosis
High index of suspicion
Proactive retention for the first 3-5 years
Initial treatment in outpatient setting
In patient if risk of aggression to self or others
In patient in least restrictive
24-48 hr wait and watch time
Commence low dose antipsychotic +/- benzo
Organic screen
Psychoeducation
Psychological treatment (CBT)
If no response with 2 antipsychotics, consider clozapine
Follow up in EPPIC or similar service
What are the risk factors for suicide in schizophrenia
Individual: Young, single, unemployed, male** Caucasian Depression and hopelessness** Previous suicide attempt** Drug and alcohol ** Insight retained** Good premorbid function** Akathisia Deteriorating physical function
Social:
Social isolation
Unemployment
Hospitalisation close to roads or railway
Principles of managing suicidal ideation in schizophrenia
1. Prompt initial assessment Emergency medical treatment as required Prompt initial assessment of SI/following attempt Psychotic sx: command hallucinations, persecutory delusions, spy/conspiracy delusions Depressive sx Access to lethal means Social support and supervision 2. Ensure immediate safety Inpatient treatment with observation Remove access to means of self harm 3. Appropriate management Management of psychosis/depression
Poor prognostic factors
poor premorbid insidious young onset cognitive impairment \+ventricle size
Good prognostic factors
Elevation during Affective Female FHx Developed country
Number who have a prodrome
80-90%
Attenuated- late prodrome
= UHR mental state
Outcomes/prognosis in FEP (after 13 years)
15-20% won't recur Few in employment 52% >2 years sx free 52% no negative sx 55% good/reasonable social function
What are the factors affecting compliance in patients
- Patient factors
- therapeutic alliance
- attitudes toward medication, family attitudes
- insight impaired
- stigma
- cultural factors - Illness factors
- delusions
- hallucinations
- cognitive impairment
- depression - Medication factors
- lack of efficacy
- side effects
- complexity of regime
- cost
Strategies to manage non-compliance
- Patient/family
- psychoeducation
- involve the family
- CBT/IPT
- compliance therapy/adherence therapy incorporating motivational interviewing - Medication
- dosette box, alarm, mobile phones, post it notes
- normalise taking
- depot - Illness
- treat illness aggressively
If patient refuses: intensive follow up, inform GP, psychoeducation for family to detect early relapse sx, ofer trial of supervised medication, rather than abrupt cessation
Terms in schizophrenia: dementia precoce, manic depressive/dementia precox/catatonia/hebephrenia, schizophrenia, first rank. Names associated
Dementia precoce- Morel
Manic depressive/Dementia precox/Catatonia/Hebephrenia- Kraeplin
Schizophrenia- Bleuler
First rank- Schneider
Principles of managing treatment resistance
- Establish true resistance
- Treat pseudoresistance
- Clozapine is treatment of choice
- Dose: 300mg min effective, levels >350
How do you manage pseudoresistance
Reassess diagnosis Rule out organic Optimise dose Serum levels Assess compliance Check for pharmakokinetic/pharmacodynamic interactions Screen for co-morbidities
What are the negative sx in schizophrenia
Abulia* Alogia* Apathy Affective blunting* Anhedonia Social withdrawal
What are the causes of negative symptoms
Primary- schizophrenia Secondary- Severe positive sx Depression, demoralisation (post-psychotic depression) Post remission exhaustion syndrome Medication/EPSE Drug misuse Organic
Crow two syndrome hypothesis
1. Mostly Positive sx Good premorbid Normal cognition Good treatment response 2. Negative sx Poor function Impaired cognition Brain structural abnormalities 3. Syndrome - psychomotor poverty - disorganisation - reality distortion
Subtypes of schzophrenia
Catatonic Paranoid Disorganised Undifferentiated Post-schizophrenia depression Residual Simple
Components of family therapy in schizophrenia
Therapeutic alliance with family Psychoeducation Address high EE Increase problem solving capacity of family Enhance communication through circular questions Boundary setting Promote individual independence Allow venting Involve family in relapse prevention
What are the components of CBT in schizophrenia
- Therapeutic alliance
- Challenging assumptions
- Reconceptualisation of symptoms
- Mood modification
- Anxiety modification
- Compliance therapy
- Coping strategies and problem solving
Techniques in adherence therapy
Use reflective listening Summarising statements Inductive questions (conclusions from observations) Explore ambivalence Use normalising rationales
Components of cognitive remediation therapy
- Assessment
- Treatment to remediate impairments
- Cognitive mediation- errorlesss learning, easy discrimination of components being learnt, individual should not experience failure, extremely gradual increase of difficulty of task to be learnt
Components and principles of social skills trainings
Social skills deficits model- deficits cause vulnerability to psychiatric illness
Stress-vulnerability model- social skills protect againts psychiatric disorder
Targets
1. Non verbal
2. Para-linguistic
3. Linguistic
Modelling, feedback and opportunities to generalise behaviour
Efficacy- Meta-analysis Schiz Bull 2006 showed skills can be learned and maintained in artificial environment, but generalisation rarely occurs, it must be programmed.
Important trials
CATIE
CutLASS
EUFEST
What are the criteria for prodromal states
Attenuated= sub threshold symptoms over period of 1 week to 5 years
Schizotypal disorder trait or first degree rel with schizophrenia + decrease in GAF over period of 1 month to 5 years
BLIPS (brief intermittent psychotic symptoms)- at least one psychotic sx for <1 week over past year
- Trait + attenuated
- Trait or attenuated < 5 years
- Trait or attenuated or BLIPS + GAF <60
Any of the above predict psychosis over 12 months
Consequences of untreated psychosis
Slower and less complete recovery Higher relapse rates Treatment resistance Increased negative symptoms Functional impairment Substance misuse Higher suicide Decreased quality of life Neuropsychological deficits
Important management points dystonia
Benztropine IV or IM 1-2mg
Important risk factors/management points pseudoparkinsonism
Can assess with Simpson-Angus rating scale
Differentiated by Parkinson’s by bilateral tremor
Risk factors: elderly females, pre-existing neurological
Reduction of dose, change to atypical if on typical, prescribe anticholinergic
Important management points akathisia
Measured by Barnes Akathisia Scale
Incraeses suicide risk
Reduce dose Change to atypical Benzt may help if other antiparkinsonian sx present Propranolol Cyproheptadine Benzo Clonidine
Important risk factors/ management points TD
Lip smacking, tongue protrusion, choreiform, pelvic thrusting
Measured by AIMS
Risks: diabetes, typicals, organic neuro, female, smoking
Stop anticholinergic
Reduce dose
Change to atypical
If untreated, clozapine
Tetrabenazine (Huntington’s)
Benzo
Vit E
Tips for restarting antipsychotic after NMS
- Wait 2 week
- Lower potency (Olanzapine, questiapine) lower dose, titrate slowly
- Avoid co-administration with Lithium
- Avoid dehydration
- Monitor for sx
NMS: sx, Ix, risks, management
Sx: Diaphoresis, fever, rigidity, fluctuation consciousness, autonomic instability (fluct BP, tachyC)
Ix: CK++, leukocytosis, altered LFTs
Risks: high potency typicals, abrupt dose change, abrupt withdrawal of anticholinergic, parkinson’s/organic, hyperthyroid, dehydration, psychomotor agitation, ID
Management:
- Medical emergency
- Withdrawl AP
- monitor vitals
- Rehydration, bromocriptine, dantrolene, benzo’s
- Cooling blankets, artifical ventilation if required
- ECT
- Restart antiP with caution
Hematological SE clozapine
Agranulocytosis
Neutropenia
TE/PE
CV SE clozapine
Myocarditis CM TachyC- high % benign Prolonged QTc PeriC Pericardial effusion Cardiac failure MV insufficiency
Core facts: prevalence, mortality, comorbidity, heritability, risk with Identical, both parents, 1 parent, genetic association
Prev: 15-19/1000
Mortality: 20% reduced life expectancy
Co-morbid: HIV/HEP B/HEP C + men in first year, epilepsy, IHD, celiac substances
Heritability: 60-80% (Neureglin, NRGI, dysbindin, DISCI, COMT Val158Met)
Identical twin- 46%
both parents- 40%
1 parent- 15%
Metabolic syndrome sx and management
Central adiposity Raised TG/LDL Reduced HDT T2DM, glucose intolerance Hypertention
Management:
1. Baseline monitoring
2. FHx obesity, DM, dyslipidemia, HTN, CVD
3. BMI, waist, BP, FGL, lipids- every 3-6 months
4. Treat with SGA with least weight gain potential
5. Psychoeducation
6. Lifestyle modification- dietician, exercise
7. Pharmacotherapy if required
(orlistat, sibutramine (MAORI), rimonabant (Cannabinoid receptor antagonist, topiramate, metformin)
Mechanism of AP induced weight gain in schizophrenia
Individual factors
- increased body fat
- alcohol
- leptin dysfunction
- ghrelin dysfunction
- insulin resistance
Meds:
- 5HT2c antagonist, H1 antagonist
- reduced energy expenditure
Characteristics of late onset schizophrenia, compared to early-onset schizophrenia
Onset >45, or >65 in very late Greater sensory impairment Social isolation Eccentric premorbid Greater likelihood of visual hallucinations Encapsulated delusions Partition delusions Greater female preponderance Greater risk of developing TD Lesser genetic risk No past hx Less formal TD Less affective blunting
Contributory factors to psychosis in old age
Sensory impairment Social isolation Neurocognitive changes, neurochemical Age related deterioration in frontal and temporal cortices Pharmacokinetic/pharmacodynamic changes Polypharmacy
Common misidentifying delusions in AD
Capgras
Phantom boarder
Mirror sign
TV sign
DSM V criteria SZP
2 or more, >1 month (must have 1,2, or 3) Delusions Hallucinations Disorganised speech Grossly disorganised/catatonic behaviour Negative symptoms Continuous disturbance for >6 months
Schizophreniform= >1month, less than 6
Brief psychotic= >1 day, <1 month
Delusional disorder= one or more delusions >1 month, and criteria A for schizophrenia has never been met
DSM V for Schizoaffective
- Major mood + criteria A of schizophrenia
- Delusions or hallucination for 2 + weeks in absence of major mood episode
- Criteria for mood are filled during active and residual periods of illness
Aetiology of schizophrenia
- Biochemical:
- DA
- Glutaminergic hyperactivity
- 5HT +(LSD, cloz)
- a-adrenergic ++
- GABA -ve (leads to + NE/5HT/DA) - Neurodevelopmental- obstetric compl, motor/cognitive problems, cerebral structure, dysmorphic
- Disconnection hypothesis= -ve grey matter, memory/frontal lobe impairment, -ve white matter in frontal lobes
