Psychosis Flashcards
1
Q
Schzophrenia DSM-5 Definition
A
DSM-5: ≥6 months + ≥ 1 month of ≥ 2 sxs.
One must be: delusions, hallucinations, disorganized speech.
Other: disorganized/catatonic behavior, negative symptoms (blunted affect, alogia, avolition, anhedonia, amotivation). ↓ social/occupational function
2
Q
Define Psychosis
A
Presence of gross impairment of reality testing (e.g. lose touch with reality) as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behavior without apparent awareness on the part of the patient of the incomprehensibility of their behavior
Schizophrenia is one of MANY causes of psychosis
3
Q
Define treatment reistant schizophrenia
A
No significant improvement in sxs despite tx with ≥ 2 APs from 2 different AP classes at optimal dose for 6-8w
4
Q
Define schizophreniform Disorder
A
1-6 months, same sxs as schizophrenia, social/occupation functional impairment not required
5
Q
Define schizoaffective disorder
A
≥2 wks of delusions or hallucinations without mood sxs + uninterrupted period of illness containing either major depressive or manic episode with concurrent sxs diagnostic of schizophrenia. Social/occupation functional impairment not required.
6
Q
Define brief psychotic disorder
A
1 day to 1 month of ≥ 1 of delusions, hallucinations, disorganized speech. Return to premorbid function.
Medication induced, acute stressor event, post-partum –> If return back to normal levels, classified as brief If dysfunction and longer than 1 month Schizoaffective
7
Q
Define Delusional Disorder
A
1 month of delusions. Hallucinations not prominent. Function only mildly impaired, behavior not blatantly bizarre.
8
Q
Define Substance Induced Psychosis
A
Hallucinations or delusions development during or within 1 month of substance use/withdrawal.
9
Q
Substance with highest risk of substance induced psychosis
A
Crystal Methamphetamine
10
Q
Define the duration of untreated psychosis
A
Time from the manifestation of the first psychotic symptom to initiation of adequate treatment
11
Q
Schizophrenia Prevalence. Onset and differences between sexes?
A
Schizophrenia prevalence: 1% in Canada. Usual onset at age 16-30 yrs (men earlier 15-24 yr vs. women 25-34). Equal distribution between sexes.
12
Q
Risk factors for Scizophrenia
A
immigrant ethnic groups
perinatal/early childhood (hypoxia, maternal infection/stress/malnutrition)
urban upbringing
cannabis use
life stress
13
Q
Does a genetic link exist in schizophrenia?
A
Genetic heritability 80%. ↑risk 15-20x if parent has schizophrenia.
14
Q
Describe some commorbidities with Schizophrenia
A
Patients with schizophrenia die 10-20 yrs earlier than avg. population:
↓ access to care, poor diet
↓ exercise
↑ obesity/diabetes (irrespective of meds)
↑ smoking 60-90% (tobacco is a high risk substance; most od use some form of tobacco)
Substance use disorders 45%
↑ CVD ~doubles in first year (not just due to antipsychotics)
Suicide 4.5%
15
Q
What is one reason for which tx with AP is crucial?
A
Risk of death ~doubles if never treated with AP
16
Q
What is a major issue pertaining to treatment of schizophrenia?
A
Medication nonadherence rates ~50-60%
17
Q
Describe the pathophysiology of Schizophrenia
A
Dopamine dysregulation is the key theory underlying the pathophysiology of the disease
Serotonin dysregulation also contributes
Modulates dopamine
Glutamate and GABA also have a role
Less clearly understood
18
Q
Describe the dopaminergic pathways of the brain
A
19
Q
What are some prodromal features of schizophrenia?
A
often recognized retrospectively after the diagnosis has been made
reclusive adolescence without close friends (e.g. not involved in school activities or teams)
not functioning well in occupational, social and personal activities
markedly peculiar behavior, abnormal affects, unusual speech, bizarre ideas and strange
–> perceptual experiences
preoccupation with religion; magical thinking; excessive writing without meaning; sensitivity and irritability when touched by others; unusual sensitivity to stimuli
20
Q
Describe the over-arching experience of schizophrenia sx
A
Complex, heterogenous disorder
No sign or symptoms is specific of schizophrenia
21
Q
Describe the 4 clusters of sx in Schizophrenia
A
Psotive Sx (psychosis)
Negative Sx
Cognitive Sx
Mood Sx
22
Q
Describe Positive Sx
A
23
Q
Describe Negative Sx
A
24
Q
Describe cognitive sx
A
25
describe mood sx
Dysphoria, Depression
Excitement, mania
26
What are some common positive Sx of Schizophrenia? Examples?
Delusions
Hallcuinations
Disorganized Thinking
Grossly Disorganized/Abnormal Motor Behaviour
Catatonia
27
Define Delusions
Fixed beliefs that are not amenable to change in light of conflicting evidence
Common themes: persecutory, referential, somatic, religious, grandiose
28
Define Hallucinations
Perception-like experiences that occur without an external stimuli
Vivid and clear with the full force and impact of normal perceptions and not under voluntary control
May occur in any sensory modality but auditory are most common in schizophrenia
29
Most common type of hallucination
Auditory
30
Describe disorganized thinking
Usually inferred from the individual’s speech
Loose associations (talk about one thing; goes all over no idea where conversation is going)
31
Describe grossly disorganized/abnormal behaviour
May manifest in a variety of ways, ranging from childlike “silliness” to unpredictable agitation
Problems may be noted in any form of goal-directed behavior, leading to difficulties in performing activities of daily living
32
Describe Catatonia
Marked decrease in reactivity to the environment
Ranges from resistance to instructions (negativism); to maintaining a rigid, inappropriate or bizarre posture; to a complete lack of verbal and motor responses (mutism and stupor)
Can also include purposeless and excessive motor activity without obvious cause (catatonic excitement)
Other features are repeated stereotyped movements, staring, grimacing, mutism, and the echoing of speech
33
Describe some negative sx of schizophrenia? Define the term?
34
What are some associated clinical features of schizophrenia?
Substance USe
Smoking
Sucidiality
35
Describe substance use in Schizophrenia
Comorbid SUD very common (~45% of patients)
36
Describe smoking in Schizophrenia. Effect?
More than 50-75% are smokers (vs. 25-30% gen pop.)
Smoking induces CYP1A2 which affects metabolism of olanzapine and clozapine
Smoking may decrease some ADEs of AP through nicotine-dept activation of DA neurons
37
Describe suicidality in Schizophrenia?
Suicide is the leading cause of premature death in patients with schizophrenia
40-50% of all patients with schizophrenia attempt suicide at least 1/lifetime
10-15% of patients with schizophrenia die by suicide
38
What are some risk factors for suicide in schizophrenia?
Risk factors: depressive sxs, young age, male, high socioeconomic status, high premorbid functioning, early onset and a chronic deteriorating course
39
How is schizophrenia diagnosed?
clinical psychiatric history
mental status exam
family/social history
medical history
physical exam
40
What are some lab and diagnostic work ups for Schizophrenia
41
What are some causes of Drug Induced Psychosis?
AMphetamine and coacine use and withdrawal
Bupropion
Caffeine
Cannabis
Steroids
Increase dopamine in mesolimbic pathway --> too mcuh dopamine, leads to positive sx (psychosis)
Chloroquine, efavirenz, ketamine –different mechanism but still dopamine mechanisms
42
Describe substance induced psychosis. WHich agents are most likely to cause psychosis in withdrawal states ?
Most likely where withdrawal can be lead to psychotics is alcohol, benzodiazepines
43
What scales can be used for assesing Schizophrenia?
44
Non-pharm TX Schizophrenia
Exercise, healthy diet, adequate sleep
Decrease substance use
Decrease caffeine/nicotine/alcohol
Support service interventions to ↑ medication adherence individualize based on patients’ needs
Establish trusting therapeutic relationship; include patient in treatment decisions (shared decision making) when possible
Community-case management (multidisciplinary team), vocational and occupational rehabilitation techniques, cognitive behavioural therapy (↑ coping and decraesed distress and negative affect)
45
What are the main receptor targets in schizophrenia?
46
describe Anti-psychotics and the receptors they work on
47
Describe the A/E associated with the different generations of AP
48
Describe the unique profiles of anti-psychotics
Despite groupings, antipsychotics are very different from each other
Overall efficacy is similar (except clozapine)
Receptor profiles & rate of dissociation from receptors relates to tolerability
Differences in metabolic pathways is important for drug interactions
49
Describe the effect of D2 Antagonism
50
Describe the effect of 5HT for anti-psychottic function
51
Where does D2 blockage and 5HT antagonism fit into doapminergic pathways?
52
D2 Blockade A/E
53
Alpha Antgonism S/E
54
Muscarinic Antgonism S/E
55
H1 Antagonism A/E
56
Hallmark of 1st Gen AP
Strong D2 Blockers
57
FGA's High Potency
High Potency FGAs = Higher risk of movement disorders
Weaker anticholinergic effect
Common meds:
Haloperidol
Fluphenazine
Perphenazine
Flupenthixol
58
Low potency FGA
Low Potency FGAs = Lower risk of movement disorders
Stronger anticholinergic effects
Highly sedating
Most common agents
Chlorpromazine
Methotrimeprazine
59
Comparison of FGA's
Methotrimeprazine - Most Sedating
Haloperidol - Most risk of EPS
60
2nd Gen AP's
61
Second GeneratioN ANtipsychotics Receptors
Developed based on different receptor activity (esp. 5HT2A/2c) in addition to D2 blockade
↓ risk of movement disorders but ↑ metabolic adverse drug effects
62
Risperidone Receptors
High affinity for dopamine (D2), serotonin (5-HT2) and alpha-adrenergic receptors
Also binds, with lower affinity, to alpha-2 and H1 receptors – not very sedating
NO affinity for muscarinic receptors
No anticholinergic side effects!
63
Risperidone Dosing Main Concept
> 8 mg OD - Behaving like FGA --> EPS s/e
64
Risperidone Formulations
oral solution, oral tablets, orally disintegrating tablets (M-tabs), and LAI
65
A/E Unique Risperidone
Increased prolactin/sexual dysfunction (more vs other SGAs) --> Highest risk of Galactorhhea
EPS (more vs SGAs; less vs haloperidol)
Possible risk of QT prolongation
66
DI Risperidone
Pharmacodynamic interactions (e.g., CNS depressants) and 3A4/2D6 interactions
67
Paliperidone MOA
Primary active metabolite of risperidone (9-hydroxyrisperidone)
68
Formulation Paliperidone
Oral: OROS technology (like Concerta)
Delivers sustained level over 24 hours
Shell will pass in the stool
Tablets
Long acting injectable
Invega Sustenna (once monthly), Invega Trinza (every 3 months)
69
Paliperidone A/E
Headache
Orthostatic hypotension (less vs risperidone)
EPS
Insomnia (more vs risperidone) or somnolence
Weight gain (less vs risperidone)
Increased prolactin/sexual dysfunction (similar to risperidone)
Anxiety
Rhinitis
Possible risk of QT prolongation
70
Drug Interactions Paliperidone
Minimal risk of drug interactions
71
Olanazpine USe
Metabolic ADEs limit initial use.
Histamine and Muscarinic Effects
72
Olanzapine Formulations
Short-acting injectable available (for inpatient use for acute agitation)
Tablets
Orally disintegrating tablets (Zydis)
Long-acting injectable available US only*
73
Olanzapine A/E
WEIGHT GAIN (>10lbs or >7% of baseline weight)
Dizziness
Sedation
Anticholinergic effects
Increased liver enzymes
Orthostatic hypotension
Increased risk of T2DM, dyslipidemia (more vs. others)
EPS (especially akathisia); dose-dependent
Possible risk of QT prolongation
74
Olanzapine D.I.
Smoking! (CYP1A2)
Pharmacodynamic interactions with drugs of similar actions, 1A2 inhibitors/inducers
75
Quetiapine Formulations
XR - OD
IR - BID
76
Quetiapine Dosing
Lower doses used for insomnia, bipolar, depression, anxiety
77
Quetiapine A/E
Headache, dizziness
Sedation / somnolence
Orthostatic hypotension
Conditional risk of QT prolongation
Weight gain
Increased liver enzymes
Increased risk of T2DM and dyslipidemia
May reduce thyroid hormone levels
78
Quetiapine D.I>
PD interactions and 3A4 interactions
79
Ziprasidone Dosing
Rapidly titrate in the first week up to 120-160mg/day in bipolar disorder or agitated/irritable patients
To avoid ziprasidone-induced “activation” syndrome
Anxiety, restlessness, insomnia, increased energy, and hypomanic-like symptoms, which develop soon after treatment initiation and occur at the lower end of the dosage range (20-40mg PO BID). Over comes these effects at higher doses due to
80
Ziprasisone Administration
Administer WITH FOOD
Meals with >500 kcal to maximize absorption & therapeutic effect
81
Ziprasidone Unique A/E
Considered to be weight neutral
Some will experience weight gain due need to take with food
Less hyperglycemia/ hyperlipidemia vs. other SGA
Dyspepsia, nausea, constipation
Conditional risk of QT prolongation
?higher risk versus other agents
Contraindicated in patients with QT prolongation, recent MI, uncompensated heart failure, or with concurrent QT prolonging drug
82
Ziprasidone D.I.
Pharmacodynamic interactions and 3A4 inducers/inhibitors
83
Asenapine Dosing
SL tablets
Initial = 5mg BID
Max= 10mg BID
84
Asenapine Coverage
EDS (for bipolar disorder)
Failed/intolerance to less costly SGA options (e.g., quetiapine and/or risperidone)
Not covered for use in schizophrenia
Because superiority vs placebo not clearly demonstrated
Not clinically used for schizophrenia
85
Asenapine A/E
Headache, dizziness
Drowsiness or insomnia
EPS
Akathisia (restless, agitation)
Suicidal ideation
Mouth numbness x 1 hr post dose (oral hypoesthesia)
Orthostatic hypotension
Minimal effect on weight, glucose, lipids
Increased prolactin
Possible risk for QT prolongation
86
Asenapine DI
PK DIs with 1A2 inhibitors/inducers; PD interactions with CNS depressants, QTc prolonging agents, etc
87
Lurasidone Benefit
Little to no metabolic concerns
88
Lurasidone Effoicacy
Efficacy established in studies up to 6-weeks
Rarely used for schizophrenia in clinical practice
Still some EPS, sedation, etc.
89
Lurasidone Metabolism
Metabolized by 3A4
Thus influenced by inhibitors/inducers of 3A4
90
Lurasidone Dose
Dose = 40mg PO daily WITH food
Titrate as needed to 120-160mg PO daily
WITH food – to increase bioavailability (350kcal)
91
3rd Generaton AP
92
Third Gen AP EFfects
↓ risk of metabolic & movement ADEs
High rates of akathisia
Aripiprazole >> brexpiprazole
93
Describe the MOA of Ariprazole
94
What is a key feature of 3rd generations AP compared to otehr regarding dosing?
All have long half-lives
95
Dosing of ARiprazole and Formulations. Half-life and titration?
96
Adeverse EFfecrs of Ariprazole
Headache
GI complaints (e.g., nausea)
Insomnia or sedation (more often activating vs. sedating)
Akathisia
Some anxiety
Minimal weight gain
EPS
Orthostatic hypotension
Suicidal behaviour
Possible risk of QT prolongation
97
Drug Interactions of ARiprazole
Monitor for PK interactions (2D6, 3A4)
98
Brexiprazole Indication and MOA
Indication: schizophrenia, MDD add-on therapy
Acts as a partial agonist at the 5HT1A and D2 and antagonist at 5HT2A (+ additional receptor effects)
99
Brexiprazole HAlf-Life
Half-life = 91 hours
100
A/E of Brexiprazole
similar to aripiprazole but less akathisia
101
Carprazine limittaions
Just introduced to the Canadian market in 2022
Limited clinical experience
Not covered by SK drug plan
+++ expensive
102
Cariprazine Receptor Action
High affinity partial agonist at D3 + D2 receptors
At low doses → higher affinity for D3 than D2
Lower affinity for D2 than aripiprazole and brexpiprazole
High affinity partial agonist at 5HT1A
Antagonist at 5HT2A, 5HT2B
D3 Receptor activity may theoretically improve negative sx and cognitive impairments
103
CAriprazine PK
104
CADTH Cariprazine Recccomendations
Unclear whether cariprazine offers clinical benefits over other treatments
Not enough evidence to show cariprazine filled a treatment gap
Additional therapy for non-responsive patients, provide greater range of dosages, lower frequency of administration, minimize adverse effects
105
Cariprazine Uses
106
Key Points for Selecting an AP
107
What occurs in first episode psychocis relating to phsyiology?
First episode psychosis destroys 10-12 cc of brain tissue
Neurotoxicity of psychosis is mediated by neuro-inflammation and oxidative stress
Each subsequent psychotic episode will destroy more brain tissue clinical deteroriation, treatment resistance, functional disability
108
When/why should long-acting injectable antipsychotics be considered?
If oral medications are effective and tolerated, may continue with oral therapy or switch to long-acting injectable depot to improve adherence (given q2-4weeks)
May be considered if a patient relapses due to non-adherence or if patient prefers injection
Paradigm shift in practice to offer depots earlier (however must first confirm oral tolerability)
109
Key Thing with LAIA
Would never start a depot without a trial of oral for a week or a few days – no way to remove depot agents – develop a/e are stuck with the agent in their system
- Before starting an agent, must always do an oral trial first
110
Benefits of LAIA's
111
Key Critical Poinmts for initiation of LAIA
Establish tolerability with oral first!
Always double check how long to overlap with oral! (different periods of overlap)
May not show up on last 4 months of PIP but may still be pharmacologically active in the patient’s body. Always double check date of last dose! (given long half-life)
Consult the product monograph or SwitchRx for information on how to switch for one depot to another.
Still need to establish oral tolerability first! (of new agent prior to depot)
112
Avilable LAIA's
Ariprazole --> 3rd Gen --> Abilify Materna
PAliperidone --> Invega SUstenna and INvega Trinza
113
ABlify MAterna
Long half-life – takes time for onset of action; needs two weeks of standard oral initiation
New initiation – two abilify injection (no way to know if oral is tolerated) risk of akathisia
114
Invega Sustenna
No oral overlap
Risperidone – can swict to Invega Sustenna
115
Invega Trinza
Invega Trinza – Need to have been on Invega Sustenna for 4 months
Very long t1/2- if present with EPS – scary
116
Anti-psychotic A/E Summary
Someone eats pussy and works avenues
117
AP Monitoring
118
Canadian Schizophrenia Guidelines
tress the importance of:
earlier treatment of symptoms
need for greater attention to the physical care of people with schizophrenia due to the reduced lifespan
greater emphasis on recovery and the need to provide personalized care rather than focusing primarily on symptomatic management
119
What is important in first episode psychosis management?
Early treatment is critical
Early detection & tx can dcrease depression, ↑ mood/cognitive scores, ↑ overall function at 10yrs
First 2-5 years of illness are critical to offset future disability and improve outcomes;
longer duration of untreated psychosis results in dcreased response to treatment.
120
TX of first Episode Psychosis
No particular AP or class found to be clinically superior in 1st episode population
usually SGA (compared to FGA: decraesed AE, decraesed discontinuation, & equal efficacy)
choose agent based on AE profile & use lowest effective dose
using a long-acting antipsychotic injection may decrease relapse vs oral therapy
121
First Episode Psychosis Tx Duration. Risk of relapse?
controversial; minimum 18 months CDN'17
Indefinite therapy reasonable
risk of relapse after first episode 82%
5x higher if not on tx & relapses have decreased response to treatment
122
First Episode PSychosis Adequate TRial
Adequate trial: 4-6 weeks @ optimally tolerated dose
123
Acute Exacerbation Mangement
124
Sx Treatment in Psychosis
Symptoms fluctuate over lifetime; target therapy to sxs
Non-psychotic symptoms such as mood changes may also be present and necessitate treatment with non-AP medications
mood stabilizers, anti-depressants
125
Benefits of Maintenance TX
Maintenance treatment contributes to relapse prevention and hospitalization rates but does not eliminate risk of relapse
Risk of re-hospitalization or death ↑ when the duration of AP tx prior to discontinuation gets longer; may relate to AP-induced neurologic changes
126
Duration of Maintenance Tx
2017 Can. Schizophrenia Guidelines suggest maintenance AP therapy for 2 yr
Possibly up to 5 years longer
127
Psychosis and SUD
SUDs are found in up to 45% of schizophrenia patients
Stimulant and cannabis use are associated with psychosis
Example: cannabis users develop psychosis 2.7 years before non-users
Substance use also results in worse outcomes
Treatment nonadherence, relapse, etc.
Often difficult to determine whether psychosis came first and substances are used for self-treatment, or whether substances have caused the psychosis
Screen all psychosis patients for SUD
128
Psychosis and SUD: Indicative of underlying psychotic disorder
psychosis persists with abstinence;
symptoms do not align with type/amount of substance used;
family hx of psychosis;
typical positive symptoms of schizophrenia
e.g. auditory hallucinations
presence of negative/cognitive symptoms
129
Psychosis and SUD: TX
No evidence of benefit for one AP over another for psychosis &
Clozapine preferred limited data.
130
Define TRS/Psychosis. How many meet this criteria?
131
First Line TX TRS
Clozapine; response rate of 30 but often underprescribed due to fear of ADE, lack of familiarity
Delaying clozapine initiation may decrease response
132
Cloazapine MOA and receptors
133
Cloazpine Efficacy. Other indications?
Most effective antipsychotic for treatment-resistant schizophrenia
30% response rate
Other uses:
Tardive dyskinesia (mixed evidence)
Bipolar disorder
Schizoaffective disorder
Psychosis in patients with Parkinson’s disease (lot less likely to cause movement effects)
134
Common s/e Clozapine
135
Serious S/E Cloazpine
136
Cloazpine Induced Agranulocytosis
Clozapine-induced agranulocytosis 1-2%
Dangerously low neutrophil count (<0.5x109/L)
Neutropenia occurs at neutrophil count <1.5x109/L
↑ infection risk
Reversible upon discontinuation of clozapine
Health Canada mandates registration of each patient into a monitoring database to detect potentially reversible agranulocytosis (2%)
Requires monitoring of CBC with differential
137
Clozapine Induced Myocarditis
Clozapine-induced myocarditis 0.06-3.88%
Mortality rate 10-23%
Inflammation of the heart muscle
Cardiomyopathy can also occur
Requires monitoring of CRP and troponin
138
Clozapine Induced Constipation
Constipation 14%
Severe constipation can lead to adynamic ileus
Mortality rate 7.3%
Requires bowel function monitoring
139
When does agranulocytosis occur?
Agranulocytosis most likely to occur in first 6 months of treatment
140
When does myocarditis occur? Monitoring?
Myocarditis most likely to occur in first 4-8 wks of treatment
Monitoring Troponin and CRP weekly x 6 weeks is 99% sensitive to identify myocarditis
141
When does cardiomyopathy occur?
Cardiomyopathy most likely to occur after months to years of treatment
142
What should be noted about mserious a/e of clozapine?
However, agranulocytosis, myocarditis and cardiomyopathy can still occur at anytime during treatment
Literature demonstrates a clear need to implement close and structured monitoring of patients on clozapine to prevent development of agranulocytosis and myocarditis
143
What is myocarditis?
Allergic-like reaction causing inflammation of the heart
144
What is cardiomyopathy?
Disease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body
145
how can Cardiomyopathy and myocarditis be monitored?
High sensitivity troponin T
CRP
146
What is agranulocytosis and reason for blood work?
147
Is agranulocytosis reversible?
reversible upon clozapine discontinuation
148
What is required by health canada regarding Clozapine?
Clozapine can only be used if hematological monitoring (CBC with diff - neutrophils) can be guaranteed AND patient is actively registered with a clozapine registry (has a clozapine “PIN #”)
Available through manufacturer-specific registries and distribution systems (e.g. CSAN – Clozaril Support and Assistance Network)
149
Clozapine Registeries Avilable
150
Monitroing of Clozapine
Weekly blood tests for the first 6 months
High risk period
Change to once every 2 weeks if “green light” has been maintained during the first 6 months of therapy and patient is clinically stable
Change to once every 4 weeks if “green light” for another 6 months
Monitoring MUST continue for as long as the patient is on clozapine and even for 4 weeks after stopping
151
Clozapine Missed Doses
Monitoring frequency does not have to be modified if therapy is interrupted for 3 days or less but dosing needs to re-titrated if miss >48 hours
Hematological testing should be resumed weekly for an additional 6 weeks if therapy is disrupted for more than 3 days
So important to always assess adherence!
152
Describe the zones of clozapine and what to do in each zone?
153
Clozapine: If in red zone?
Non-rechallengeable =
Must stop and cannot ever restart therapy if total WBC <2.0 x 109 or ANC <1.5 x 109 from clozapine therapy
Must be communicated with clozapine registry
Will require weekly CBC x 4 weeks when stopped
Likely would be done more frequently than weekly when patient is neutropenic (patient would be hospitalized)
154
Key Critical Point for dispensing of clozapine?
Also quantity of clozapine dispensed must be limited to the frequency of clozapine bloodwork
i.e. patient on q2weekly blood work can only have 2 weeks of clozapine dispensed from community pharmacy
155
Can clozapine be switched to a generic?
Do NOT switch between brand/generics
paid by the government
156
How does smoking interfere with clozapine?
Smooking reduces clozapine by 40%
1A2 Induction
Does not occur via nicotine rather aromatic hydrocarbons
157
Clozapine Augmentation
Multiple clozapine augmentation strategies but lim. consensus on best
Data for aripiprazole, fluoxetine, sodium valproate for total psychosis, memantine for negative symptoms
158
Clozapine Resistant TRS and AP use
No consistent evidence to support use of high dose AP, switching APs, or AP polypharmacy
159
Non-Pharm TRS
ECT if clozapine resistance; Trans Magnetic Stimulation less evidence but better tolerated than ECT; Cognitive Behavioural Therapy.
160
Acute EPS Sx: How do they occur?
o Most are due to dopamine (D2) blockade
o Involuntary
161
What dos tardive mean?
Appearing late; after 30 days
162
WHy are tardive sx concerning?
Often permemenant
163
When do acute EPS side effects occur?
Within 30 days
164
TX of Acute EPS
Respond to antiparkinsonian drugs (except akathisia which may be mediated by alternate mechanism and thus responds to other treatments)
165
Tardive Syndrome TX
Valbenazine and deutetrabenazine are FDA-approved drugs for treating tardive dyskinesia (TD). No other medication or strategy have proven efficacy in clinical trials.
PREVENTION is key!
166
Tardive Sx TX Facts
Early recognition and discontinuation of offending antipsychotic are recommended to improve chance of remission but stopping antipsychotic is not always an option
Dosage reduction or use of lowest effective dose is an another alternative but the success of dosage reduction or cessation has not been proven and must be weighed against the risk of relapse
If medication is stopped or dose reduced, a slow taper is recommended to avoid worsening TD due to withdrawal emergent syndromes
Switching to atypical antipsychotics such as clozapine/quetiapine has been recommended but high doses of atypical may also cause TDs
Anticholinergic agents: No benefit and may worsen TDs (may benefit tardive dystonia)
167
Acute Dystonias Summary
Head and neck torsions and spasms
Occurs within 24-48 hours of the first dose. Can be tardive.
May be life-threatening if laryngeal/pharyngeal involvement
1st line: benztropine. Can also use IM diphenhydramine
168
Acute dystonia Scale
Extrapyramidal Symptom Rating Scale (ESRS)
Simpson Angus EPS SCALE (SAS)
169
Akathesia, Tx and Rating Scale
Restless symptoms, can cause violent outbursts
Can be tardive
Contributes to suicide and violence
Treament: reduce dose or change AP, benzodiazepines, beta-blockers, mirtazapine
Use the BARS scale to monitor
170
Acute pseudoparkinism
Tremors, rigidity, brady kinesia
Biggest risk if high potency FGA
Treatment: reduce dose/change AP, antiparkinsonian drugs
Same rating scales as acute dystonias
171
Pisa Syndrome
Leaning to one side
Treat with antiparkinsonian drugs
Antiparkinsonian drugs (benztropine, procyclidine, trihexyphenidyl)
172
Rabbit Syndrome
Fine tremor of lower lip
Treat with antiparkinsonian drugs
Antiparkinsonian drugs (benztropine, procyclidine, trihexyphenidyl)
173
Tardive Dyskinesia
Involunary abnormal movements of the face, lips, jaw, tongue, eyelids, limbs, trunk, neck, or respiratory
Onset after 3 or more months of therapy
Persistent, does not go away when you stop the AP
Treatment: switch to SGA or TGA?
Valbenazine and deutetrabenazine
Use AIMS scale to monitor
174
What is neuroleptic malignant syndrome? Sx, Time it occurs, TREATMENT?
175
Drug Interactions Chart
