Week 2: Schizophrenia, Depressive Disorders Flashcards
Schizophrenia (SPh: my abbreviation)
chronic mental disorder that affects the way a person, thinks, acts, expresses emotions, and perceives reality
DSM 5 Criteria for SPh
must have 2 or more of the following, each present for a significant portion time during a 1 month period ( or less if successfully treated. at least one must be
1.delusions (fixed false belief)
- Hallucinations
- Disorganized speech (frequent derailment or incoherence).
- Grossly disorganized or catatonic behavior
- negative symptoms (i.e diminished emotional expression or avolition
*note: for significant portion of the time since onset of disturbance, level of functioning in one or more areas such as work, interpersonal relations, or self-care, is markedly below the level achieved prior to the onset
Schizoaffective disorder
uninterrupted period of illness during which there is a for mood epode (depression or manic)
delusions or hallucinations for 2 or more weeks in the absence of major mood episode during ht lifetime of the illness
SS that meet criteria for major mood episode are present for the majority of the total duration of the illness
disturbance not attributable to the elects of a substance (
Diagnosis of SPh
- complete patient history
- Mental Status Exam
*Rating Scales: PANSS (Positive and negative Syndrome Scale)
*Brief Psychiatric Rating Scale - rule out other conditions (Physical, Labs) and co occurring disorders to establish correct diagnosis
Drugs:
*coticosteroids
*stimulants
*marijuana
*DA-Augmenting agents
*Hallucinogens
Diseases:
hiv/aids
EPILEPSY
cva/tbi
infections
Huntingtons disease
Diagnosis of SPh
- complete patient history
- Mental Status Exam
*Rating Scales: PANSS (Positive and negative Syndrome Scale)
*Brief Psychiatric Rating Scale - rule out other conditions (Physical, Labs) and co occurring disorders to establish correct diagnosis
Drugs:
*coticosteroids
*stimulants
*marijuana
*DA-Augmenting agents
*Hallucinogens
Diseases:
hiv/aids
EPILEPSY
cva/tbi
infections
Huntingtons disease
Positive symptoms
Hallucinations
delusions (fixed false beliefs)
ideas of influence (actions are controlled by external forces
disorganized speech
negative symptoms
flat Affect ( (no emotional expression)
alogia (inabilit to carryon a logical conversation)
Anhedonia (inability to experience pleasure int things you used to (depression)
Avolition( lack of motivation )
Cognitive symptomsOF-Schizophrenia
impaired attention
impaired working memory
impaired executive function
SPh Treatment
Non Pharm
comprehensive psychosocial services are needed in addition to psychotropic medication management to achieve success such as…
psychosocial rehabilitation
pshycoeducation
Therapeutic Alliance
Active community treatment…etc.
What are among the most important factors in choosing an aNTIPSYCHOTIC AGENT for an individual patient
- SIDE EFECT PROFILES
others include….
*drug interactions
*family history
*adherance
*cost
General Approach to Choosing therapyFOR-SCHIZOPHRENIA
- SE and other considerations drive choice since differentiating APS based on efficacy is challenging
- optimize mono therapy(facilitate balance between efficacy and SE)
- Combo drug therapy reserved for treatment resistant pts. (lack of evidence supporting polyp harm, but risks well known, such as non adherence)
- Clozapine For treatment resistance or earlier use indicated for suicidal pts.
- long acting injectables for those who prefer them
Patho of Dopamine antagonism at different sites
Nigrostiratal
*function: extraparymidal system, movement
*effect: movement disorders
Mesolimbic:
function: emotional function, motivational behavior
effect: relief of psychosis
Mesocortical;
function:cognition, executive function
effect: Akathisia (inability to remain still), relief of psychosis
tuberoinfundibulnar
function: prolactin release
effect: increased prolactin
Treatment considerations for stabilization and maintenance-in-MDD
full efficacy could take 6-12 weeks or longer, 3-6 months for chronically ill pts.
partial responders would be evaluated for adherence
1st episode treatment:
12 months after remission, continue treatment, chronic lifelong therapy in most pts
treatment resistance: lack of improvement with at least 2 APS from diff classes at optimal dose for at least 8 weeks (some guidelines fewer)
rating scales to track progress
gradual discontinuation unless pt experiencing severe ADR
for switching agents, gradual taper off while other agent is slowly titrated up
treatment resistant-schizophrenia
lack of improvement with at least 2 APS from diff classes at optimal dose for at least 8 weeks (some guidelines fewer)
First Generation Antipsychotics
(Typical)
Chlorpromazine (Thorazine)
Fluphenazine (Prolixin)
Haloperidol (Haldol)
Perphenazine (Trilafon)
Thiordazine (Mellaril)
Thiothixene (Navane)
END-IN-ZINE-EXCEPT-HALOPERIDOL-AND-THIOTHIXENE
FGA class related side effects-and-BWW
extrapyrimdal side effects
Qtc prolongation
prolactin elevation
dermatologic
photosensitivity
blue-gray skin
orthostatic hypotension
altered thermoregulation
BBW: dementia related psychosis (i..e elderly pts with dementia
Black Box warning for FGA
Elderly patients with dementia related psychosis treated with FGA increased risk of death
DOES NOT MEAN IT CANNOT BE USED, careful monitoring must be done. benefit should outweigh the risk. can start with smaller dose
this BBW does not include the use of FGA in elderly pts with hx schizophrenia who was on long term treatment
Second Genration Antipsychotcs
Aripiprazole (Abilify)
Brexiprazole (Result)
Asenapine (Saphris)
Olanzipine (Zyprexa)
Cariprazine (Vrylar)
Clozapine (Clozaril, Fazaclo)
Iloperidone (Fanapt)
Lumateperone (Caplyta)
Lurasidone (Latuda)
Paliperidone (Invega)
Risperidone (Risperdal)
Ziprasidone (Geodon)
Quetiapine(Seroquel)
SGA (Atypicals) SE profile
Metabolic effects
*hypertriglyceriideemia
*hyperglycemia
*weight gain (waist circumference)
qtc prolongation
blood dyscrasia/neutropenia (most common offender clozapine)
decreased seizure threshold
anticholinergic effects (such as constipation(clozapine big offender)
sedation
prolactin elevation
opthalmic effects (quetiapine big offender)
Suggested Schizophrenia pharmacotherapy algorithm
Stage 1:
*Treatment naive: any antipsychotic except clozapine
(and olanzipine due to extensive SE profile)
*previously treated w. an APS, and treatment is being restarted : any app except clozapine or previous med that had poor efficacy or intolerance
…
NO IMPROVEMENT IN 2-4 WEEKS
…
Stage 2:
*inadequate response to above
*any psychotic (not used above) except clozapine
NOTE: Clozapine may be considered in severly suicial, EPS, hx violence or substance abuse
…
NO IMPROVEMENT IN 2-4 WEEKS
…
Stage 3:
*inadequate response to above
*considered treatment resistant
*Clozapine mono therapy
Stage 4:
* Inadequate response to above
*can use alternative antipsychotics, augmentation(mood stabilizers, APS polyp harm, etc.)
Note: A;WAYS VERIFY ADHERANCE. Use of Long acting injectables can be considered if poor adherence
treatment considerations for clozapine
extensive monitoring.
labs drawn
office visits once a week for first 6 mo.
every other week for next 6 months.
then once ammonite
Long acting Injectables treatment considerations
- good for non adherent patients: HOWEVER, NON ADHERANCE SHOULD NOT BE DUE TO SE PROFILE
*stabilization on oral therapy best approach
oral challenge of the same drug before initiating LAI us best practice
most LAI do not take immediate effect, overlap is often needed, there are exceptions
FGA TREATMENT potencies
High
(Haloperidol:Haldol)
FLuphenazine ( Prolixin)
Moderte/ high
Thiothixine (Navane)
Trifluoperazine (Stelline)
Medium moderate
Lozapine
Molindone
Perphenazine
Low potency
Chlorpromazine
Thioridazine
what is the importance of potency
potency effects both EPS risk and anticholinergic risk
Trend of anticholinergic and EPS risk with High vs Low potencies
Low potency:
increased anticholinergic risk
decreased EPS risk
High potency:
increased EPS risk
decreased anticholinergic risk
Aripiprazole (Abilify)
Unique MOA:
Generation:
Dosage form Availability and notes
Unique MOA: partial D2 and 5HT1A agonist
Generation:second generation
Dosage form Availability:
PO tab
LAI: Maintena: 14 day overlap
Aristada: 21 day overlap
Mycite
Apripiprazole (abilify clinical pearls
IMPULSIVITY: MUST COUNSEL
little weight gain
may cause insomnia, akathisia, restlessness,
pts and caregivers should be alert for uncontrollable and excessive urges
Asenapine (Saphris)
Unique MOA:
Generation:
Dosage form Availability and notes
Unique MOA: high affinity antagonism D2 sand 5HT2a
Generation: SECOND GENERATION
Dosage form Availability and notes;
Topical Patch: wear for 24hours upper arm back, abdomen, or hip. can shower but cannot win, don’t apply heat
Sublingual tablet: must counsel cannot eat or drink for 10 min
Asenapine (Saphris)
Clinical Pearls
NEW TOPICAL PATCH AVAILABLE
among least anticholinergic and less sedating
do not eat or drink after SL dose for 10 min
high risk of QTC prolongation.
CI: severe hepatic disease
topical patch may cause skin irritation
anaphylaxis may occur after single dose
Brexipprazole (Rexulti)
Unique MOA:
Generation:
Dosage form Availability and notes
Unique MOA: partial 5HT1A and D2 receptor agonist and 5HT2A receptor antagonist
Generation: second generation
Dosage form Availability and notes: oral tab only
Brexipiprazole Clinical pearls
IMPULSIVITY
dose related Akathisia,
long half life (91 hours)
Fewer metabolic changes than others
Clozapine (Clozaril)
Unique MOA:
Generation:
Dosage form Availability and notes
Unique MOA: antagonist of D1 ad D4(D2 less, 5-HT2 and others, M4 for agonist
Generation: second
Dosage form Availability and notes:
PO tablet
ODT (oral disintegrating tablet)
Oral solution:
ODT and oral EXPENSIVE. NOT usually covered by insurance
Clozapine clinical pearls
gold standard for treatment resistant schizophrenia or earlier if pt has high suicidal risk
BLOOD DYSCRASIA
HIGH METABOLIC RISK
CONSTIPATION-can lead to bowel obstruction. can lead to hospitalization or death.
DDI: Clozapine/ olanzapine use with benzos(especially lorazepam IM)
monitor ANC(absolute neutrophil count) levels as per REMS monitoring
REMS monitoring program
first 6 mo. q week
every other week for next 6 mo.
every month thereafter
Illoperidone
Unique MOA:
Generation:
Dosage form Availability and notes
Unique MOA: high affinity D2, D3, and 5ht2a
Generation: SECOND
Dosage form Availability and notes
PO
Illoperidone (Fanapt)
clinical pearls
ORTHOSTATIC HYPOTENTION. slow titration needed
no notable prolactin elevation reported
qtc prolongation
LLOWWWWW-BP
Lorasidone (Latuda)
Unique MOA:
Generation:
metabolism
Dosage form Availability and notes
Unique MOA: antan: D2 and 5HT2a
Generation:second
metabolism: cyp3a4
Dosage form Availability and notes: PO
Lorasidone (Latuda)
clinical Pearls
DO NOT USE WITH STRONG CYP3A4 inhibitors/inducer
alsoindicated for use in adolescents
indicated for depression associated w. bipolar disorder or in adolescents with major depressive episodes
Lumateperone (Caplyta)
Unique MOA:
Generation:
Dosage form Availability and notes
Unique MOA:
Generation: second
Dosage form Availability and notes:
oral capsule
Lumateperone Clinical Pearls
DO NOT USE WHEN BREASTFEEDING
may impair fertility especial if taken in 3rd trimester
Olanzipine (Zyprexa)
Unique MOA:
Generation:
Dosage form Availability and notes
Unique MOA:
Generation: SECOND
Dosage form Availability and notes
PO,
ODT
short acting IM
LAI (Relprevv): requires 3 hr observation period due to post injection delirium and sedation
Olanzipine (zyprexa)Treatment-considerations
can cause DRESS
METABOLIC ISSUES
post injection delirium-PDSS REMS PROGRAM FOR LAI
Qtc-risks
sedation
anticholinergic
Paliperidone (Invega)
Unique MOA:
Generation:
Dosage form Availability and notes
Unique MOA:
Generation:
Dosage form Availability and notes:
PO: OROS TABLET,LAI
Paliperidone clinical pearls
EPS
Prolactin
No PO overlap required for LAI
med shell may be seen in stool