10 - Schizophrenia Flashcards Preview

Year 3 - Clinical (Winter) > 10 - Schizophrenia > Flashcards

Flashcards in 10 - Schizophrenia Deck (34)
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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  • Persons w/ SZP are often fearful, withdrawn, isolated, & have gross impairment of capacity for relationships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  • Usually prodromal features – “odd”, suspicious, withdrawn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