10 - Schizophrenia Flashcards
1
Q
Schizophrenia
A
- Usually chronic, often severe & disabling brain disorder
- Broad spectrum of presentation, & of functional impairment
- Persons w/ SZP are often fearful, withdrawn, isolated, & have gross impairment of capacity for relationships
- Heterogeneous disorder involving thought, behaviour, affect (mood), perception, cognition, abnormal interpretation of reality, impaired function
2
Q
SZP clinical course
A
- Usually prodromal features – “odd”, suspicious, withdrawn
- “1st break” between 18-28 y
- Suicide risk highest in 1st 5 years, may be 15% lifelong
- Chronic disorder w/ few or many exacerbations & recoveries
- Wide range of functional status/ capacity
- Sx may change over time
3
Q
SZP NT features
A
- Relative dopaminergic excess in mesolimbic & mesocortical areas correlate w/ psychotic sx
- Relative dopaminergic shortfall in frontal lobes correlates w/ negative & cognitive sx
- Roles of glutamate, GABA, serotonin apparent but not yet well defined
4
Q
Define neurosis and psychosis
A
- Neurosis = characteristics or trait, perhaps odd but unlikely “pathologic”
- Psychosis = abnormal mental state/ sx (a NOW descriptor)
5
Q
SZP sx clusters
A
- Positive –> hallucinations, delusions, illusions, anxiety, restlessness, hostility, bizarre actions/ statements, paranoia, suicidal
- Negative –> lack of pleasure in everyday life, diminished ability to initiate & sustain planned activity, immobile facial expression, poverty of speech (minimal & simplistic content, flat monotonous voice)
- Cognitive –> poor insight & judgement
- Cognitive impairment often related to prolonged neurotransmission imbalance, & impacted by acute sx
- Positive = personality traits that shouldn’t be there; negative = traits that should be there & aren’t fully expressed
6
Q
Describe SZP hallucinations
A
- Common sx of SZP
- May experience in 1 or more of the senses (auditory, visual, tactile, olfactory)
- “Voices” – most common, may be multiple & varied in nature
- May be present only in exacerbations or may persist in some form on a chronic basis
- Command hallucination = “voices” tell person they must do something in order to prevent something; very dangerous
7
Q
Describe SZP delusions
A
- False, often fixed beliefs which persist despite “proof” of falseness or impossibility
- May be paranoid, bizarre, grandiose
- Response to even favourable tx may be limited or poor
8
Q
SZP thought disorder
A
- Disorganized, illogical
- Abnormal interpretation of reality
- Garbled speech
- Thought blocking or “removal”
- Made up words
9
Q
Movement disorders w/ SZP
A
- May accompany acute exacerbations
- Clumsy, uncoordinated
- Involuntary movements, grimacing
- Repetitive/ unusual patterns
- Rarely catatonic
10
Q
Functional impairment w/ SZP
A
- Cornerstone of diagnosis, assessment, and tx and support
- Dysfunction often related primarily to impact of negative and cognitive sx
- Degree of impairment correlates w/ time & severity of poorly-controlled sx
- First 5 years after dx are critical
11
Q
Diagnostic factors for SZP
A
- Deterioration of function
- 6-month duration of sx, features
- Onset before 45 y/o
- Rule out – affective disorders, organic disorders, substances, subtype of developmental delay
12
Q
Lifelong major goals of therapy for SZP
A
- Prevent harm
- Bring thoughts and behaviour under px control
- Restore contact w/ reality
- Maximize functional recovery
- Prevent relapse
13
Q
Phases of SZP tx
A
- Initial (acute)
- Stabilization
- Maintenance & recovery
14
Q
Antipsychotic drug options
A
- 1st gen antipsychotics (FGA) = typical, traditional
- 2nd gen (SGA) = atypical, novel
- So called “3rd gen” = mixed; dopamine antagonist/ agonist effects
15
Q
Geriatric concerns w/ antipsychotic medication
A
- Hazardous side effects – sedation, orthostasis, falls
- Increased sensitivity; decreased clearance capacity
- Poor “secondary” indications – wandering, belligerence, hypnotic
- May be helpful for agitation, aggressiveness, unsafe behaviour
- Warnings for SGAs & FGAs
- Consider alternatives – BZD, mood stabilizers, beta-blocker & start low, go slow
16
Q
SZP/psychosis – initial goals and tx for acute psychosis
A
- Ensure safety, prevent harm
- Prevent rapid & severe decline
- Secondary goals = reduce agitation, hostility, anxiety, suffering; normalize sleeping & eating pattern; convey empathy & caring
- Early effects often include reductions in agitation, anxiety, hostility, distress
- Hallucinations may remain intact but w/ lessened intensity, frequency, persistence, individual distress
- BZD may allow for minimal antipsychotic use
- FGA or SGA may be preferred
- Positive sx, anxiety, harm reduction are the targets of initial or acute management
17
Q
Acute agitation - medication
A
- BZD may be first line
- BZD + antipsychotic = yellow standard for agitation
- If hx is clear and high risk for harm – may need to consider zuclopenthixol, quite sedating on 1st exposure, 24-72 h duration of calming effects
18
Q
Stabilization phase tx for SZP
A
- Slow, often erratic improvement over 3-12 weeks (highly variable); focus often has to remain on positive sx
- 1-3 weeks –> look for decreased intensity of hallucinations, paranoia; improvements in self-care, anxiety, socialization
- 3-12 weeks –> further improvements, likely discharge when “safe” but improvement/ regression dependent on ongoing adherence
- Negative sx usually a much slower response & often more resistant to medication than positive sx
19
Q
Pharmacist’s role in SZP tx
A
- Don’t reinforce stigma
- Support therapeutic alliance on illness
- Don’t assume the indication; you would prefer to be treated as an individual, not be defined by an illness
- Non-judgmental questions to guide counselling
- Listen!
- Optimal timing of meds; simplification; adverse effect management advice & strategies
- Supporting the pt is more critical than adding to overwhelming info
20
Q
Pt counselling for SZP
A
- Discussing the chemical imbalance may help to relate to medical illness
- Sets up dialogue for “every day” medication (instead of when they feel bad)
- May decrease self-stigma
21
Q
First gen antipsychotics for SZP – MOA, potency, SE, limitations
A
- Efficacy tied to dopamine receptor blockade (D2)
- Effective, but many consider 2nd line for “new” px
- “Potency” refers to D2 receptor binding affinity; potentially “equi-effective” regardless of D2 blockade “potency”
- Tolerability and outcome are the keys
- SE = anticholinergic (dry eyes, dry mouth), CV (postural hypotension), sedation, neurologic (movement disorders; D2 antagonism decreases seizure threshold), prolactin elevation (men – gynecomastia, dysfunction in libido; women – menstrual disturbance, hirsutism, osteoporosis; don’t want to elevate prolactin for long periods), neuroleptic malignant syndrome (rare, can be life-threatening, pt becomes rigid)
- Tx limitations = negative & cognitive sx often respond poorly
22
Q
Extrapyramidal movement disorders (EPS)
**probably on midterm
A
- Dystonic reactions – uncoordinated/ spastic innervation of a muscle group
- Akathisia – motor restlessness, pacing
- Akinesia – decreased muscular movements
- Rigidity – trunk, limbs, digits, facial
- Tremors – may include pill rolling, rabbit syndrome
- Tardive dyskinesia – occurs later on; easiest way to treat is to prevent
23
Q
EPS management
A
- *Prevention and early detection
- Anticholinergics
- Propranolol for akathisia
- BZDs for akathisia and other EPS
24
Q
Second gen antipsychotics – first line agents, SE, MOA
A
- Broader impact on serotonergic and dopaminergic transmission (receptors)
- Different SE profiles; less movement disorders, but greater metabolic issues
- All SGAs offer improved impact on negative sx, demonstrated effect on positive sx, and alternatives for poor responders
- First line = risperidone, olanzapine, quetiapine, ziprasidone
25
Q
SGA clozapine – MOA, compared to FGA, downside, general dosing, contraindications
A
- High 5HT2 affinity and low D2 affinity (ratio 20:1)
- If pt stops, sx can come back quickly b/c D2 receptors open up quickly
- Vs FGA –> broader spectrum of efficacy (especially tx resistant px and negative sx); decreased risk of EPS & tardive dyskinesia; no prolactin effects; no up-regulation of D2 receptors (tardive effects)
- Downside = agranulocytosis, not dose-related so requires mandatory CBC’s (originally weekly, then can go to q2weeks or q4weeks); drowsiness, hypersalivation, tachycardia, dizziness; constipation; seizure risk; weight gain/ metabolic issues
- Started at very low doses relative to the maintenance dose
- Not 1st line agent but has best results for px w/ “tx-resistant” SZP & in suicide risk
- Adequate trial should be minimum 3 months, but ideally 6 months or longer in tx-resistant populations
- Contraindicated in px w/ hx of drug-related blood dyscrasias or poorly-controlled seizure disorders
26
Q
Risperidone - MOA, compared to FGA, compared to other SGAs
A
- Potent 5HT2 and D2 blocker; affinity 5HT2 > D2
- Vs FGA –> broader spectrum of efficacy; less EPS but advantage becomes smaller as dosage rises; improved tolerability
- Vs other SGA –> strongest and tightest D2 affinity and binding; implications on adherence gaps, EPS, and prolactin-related AE; least sedating
27
Q
Paliperidone advantages
A
- Simplified dosing but less flexibility
- Food can increase Cmax and AUC
- Less potential for P-450 interactions; less prolactin effects/ weight gain (compared to risperidone)
- Likely worth the extra cost for select px
28
Q
Olanzapine - MOA, compared to other SGA, SE
A
- High affinity for multiple receptors (M1, 5HT2a, H1, 5HT2c, D2)
- t1/2 allows for once daily dosing
- Smoking increases clearance; nicotine actually helps some sx
- SE = somnolence, dizziness, weight gain, metabolic syndrome; seizure risk low, similar to FGAs
- Can be dosed around dinnertime to get sedative effects around bedtime
- Both olanzapine and quetiapine have hypnotic (for sleeping) and anxiolytic effects
- Starting dose very close to target dose; risk for EPS increase at doses > 20 mg/d
- Vs other SGAs –> increased metabolic & weight effects (**biggest reason why guidelines moving away); expensive acquisition cost; sedation, anxiolytic
29
Q
Quetiapine – MOA, SE, XR formulation, compared to other SGAs
A
- High affinity for multiple receptors; much lower affinity and looser binding at D2
- May or may not be able to give as a single daily dose at HS (some people still experience sedation in the morning, so would split up the dose for these px)
- SE = can be very sedating; dry mouth, tachycardia, akathisia, tremor
- XR formulation –> prolong Tmax; some reduction of adverse effects; extends action at D2 receptor somewhat; best depression evidence of SGAs for this formulation
- Vs other SGAs –> sedation (can be either intolerable or advantageous), anxiolytic, some weight gain (less than olanzapine), multiple tablets (may be obstable or benefit), not all px manage once daily
30
Q
Ziprasidone – MOA, drug interaction, advantage
A
- Highest 5HT2a: D2 affinity ratio
- Bioavailability 60% w/ food
- Main drug interaction = QTc prolongation
- Favourable metabolic profile (weight gain, BG, lipids) compared w/ other SGAs, but success rate may be inferior to other SGAs and FGAs, so utilization currently low
31
Q
Aripiprazole - MOA, advantage
A
- Perhaps “third generation” b/c has mixed antagonist/ agonist effects at dopamine receptors
- Fewer metabolic effects than clozapine, olanzapine, and quetiapine
- Effective for SZP, but largest role is augmentation of antidepressant tx (lower dose)
32
Q
Lurasidone - MOA, SE, other indication
A
- Antagonizes 5HT2 and D2; partial agonist at 5HT1A; minimal effects at H1, MI (cholinergic)
- “Modest” metabolic effects
- Most frequent SE = drowsiness, akathisia, nausea, parkinsonian, agitation
- Also indicated for bipolar depression
33
Q
SZP maintenance tx
A
- Usually considered a chronic disease or condition of NT imbalance; lifelong tx may be best
- Adherence to tx correlates w/ both reduced relapse risk and w/ continued functional improvement
34
Q
Antipsychotic combinations
A
- Increased adverse effect and cost w/ minimal evidence to support
- Case reports include moderate to major benefits in isolated px
