Schizophrenia & Antipsychotics Flashcards
Schizophrenia criteria for diagnosis
Must have 1 of delusions, hallucinations, or disorganized speech
Anosognosia
Patient lack of awareness or insight into schizophrenia illness
Occurs in about 57-98%
Most common predictor of nonadherence
Positive symptoms
Antipsychotics most effective
Clinically significant = acute phase schizo
Hallucinations
Delusions
Paranoia/suspiciousness
Conceptual disorganization
Hostility
Grandiosity
Excitement
Loose associations
Thought broadcasting
Thought insertion
Negative symptoms
Antipsychotics may not be completely effective
Flat affect
Social withdrawal
Lack of personal hygiene
Prolonged time to respond
Poor rapport
Poor abstract thinking
Lack of spontaneity, flow of convo
Emotional withdrawal
Ambivalence
Asociality
Amotivation
Anhedonia
Cognitive symptoms
No current medications effectively treat
Poor executive function
Impaired attention
Impaired working memory (does not learn from mistakes)
Stages of Schizophrenia
Prodromal (gradual development of symptoms but not super noticeable)
Acute (clinically significant positive sypmtoms)
Stabilization (acute phase decreasing)
Stable (positive symptoms declined, possible to have negative or cognitive symptoms)
Neurotransmitters involved in schizophrenia
Dopamine
Serotonin
Glutamate
Low potency FGA
Chlorpromazine
Thioridazine
Low potency = low affinity for DA receptor = more drug available to go to other receptors = more side effects
AC = Sedation = OH > EPS
Moderate potency FGA
Loxapine
Perphenazine
Trifluoperazine
Moderate AC, sedative, OH, EPS ADE
High potency FGA
Haloperidol
Fluphenazine
Pimozide
Thiothixene
EPS»_space;> AC = sedative = OH
FGA side effect based on receptor
Anticholinergic: dry mouth, constipation, blurred vision, urinary hesitancy
Antihistamine: sedation (dose related)
Alpha blockade: orthostatic hypotension
Dopamine blockage (in nigrostriatal pathway): EPS, hyperprolactinemia
SGA Partial dopamine agonists
Aripiprazole
Brexipiprazole
Cariprazine
Stabilizes dopamine transmission
SGA with D3 receptor blockade
Cariprazine - may have benefit at negative and cognitive symptoms
Aripiprazole
SGA with serotonin 1A partial activity
Aripiprazole
Brexipiprazole
Cariprazine
»
Clozapine
Quetiapine
Ziprasidone
May benefit cognition, decrease EPS, and improve mood
Monitoring parameters for ALL SGAs
Baseline & periodically
BMI
Blood pressure
Fasting glucose
Lipids
Waist circumference
Antipsychotics with highest risk of weight gain, diabetes
Olanzapine
Clozapine
> > >
Quetiapine
Risperidone
Low potency FGA > High potency FGA
SGA with no EPS
Lumateperone (caplyta)
SGA with no glucose or lipid effect
Lumateperone (caplyta)
Most sedating SGA
Clozapine
Quetiapine
SGA with most orthostasis
Clozapine
Iloperidone - has strict titration schedule to minimize OH
SGA with warning for suicidal ideation
Aripiprazole
Brexipiprazole
Cariprazine
Lumateperone
Lurasidone
Quetiapine
These are also used for treatment of mood disorders (depression)
Pseudoparkinsonism
EPS
Bradykinesia, rigidity, tremor, akinesia
- Reduce dose
- Change to another antipsychotic with less risk
- If cannot change, add on diphenhydramine, trihexyphenidyl, benztropine
SGA with highest Parkinsonism risk
Paliperidone
Risperidone
Lurasidone
Olanzapine
Parkinsonism Risk Lay On
Dystonia
Acute EPS - usually from high dose parenteral agents
Torticollis, laryngospasm, oculogyric crisis (upward deviation of both eyes)
- Treat using IM anticholinergics
- Prevent with PO anticholinergics
Akathisia
EPS
Restlessness, inability to stay calm
- Reduce antipsychotic dose
- Change to agent with less risk
- If unable, lipophilic BB
- If cannot do BB, then benzo, mirtazapine, trazodone, cyproheptadine
Responds POORLY to anticholinergics!
SGA with low akathisia
Clozapine
Iloperidone
Quetiapine
Tardive Dyskinesia
EPS
Abnormal, involuntary movements of orofacial muscles. May be irreversible.
Risk highest with high doses, >54 y/o, women
- Lower dose
- Change agent - but caution as their disease may be stable at the current agent
- Use Valbenazine or Deutetrabenazine
DO NOT GIVE ANTICHOLINERGICS
Agents with lowest Tardive Dyskinesia Risk
Clozapine – not associated with TD.
SGAs have low potential
Valbenazine (Ingrezza)
VMAT2 inhibitor used for TD
Adjust for strong CYP3A4, 2D6 inhibitors
ADR: sleepiness, depression, QTc prolongation
Deutetrabenazine (Austedo)
VMAT2 inhibitor for TD
Adjust for strong CYP2D6 inhibitors
ADR: sleepiness, depression, QTc prolongation
BBW: increased risk of suicide
Neuroleptic Malignant Syndrome
Medical Emergency
Agitation, confusion, muscle rigidity, fever, tachycardia, autonomic instability, diaphoresis
- D/C Antipsychotic
- Supportive cares
- Bromocriptine or dantrolene
- Wait at least 14 days before restarting antipsychotic
Highest risk with high potency FGAs
Hyperprolactinemia highest risk and lowest risk
Breast enlargement, galactorrhea, sexual dysfunction, infertility, menstrual changes
Highest risk: FGAs, risperidone, paliperidone
Aripiprazole may lower prolactin concentrations
QTc prolongation
Chlorpromazine
IV haloperidol
Thioridazine
Clozapine
Ziprasidone
Iloperidone
Antipsychotics that lower seizure threshold
Chlropromazine
Cariprazine
Clozapine
Antipsychotics with lowest seizure risk
Aripiprazole
Fluphenazine
Haloperidol
Pimozide
Rispseridone
Thioridazine
Trifluoperazine
CYP1A2 substrates, inducer, inhibitor
Sub:
Clozapine
Asenapine
Ziprasidone
Olanzapine
Inducer:
Cannabis
Tobacco
Inhibitor:
Caffeine
CYP2D6 sub, inhib
Substrate:
Brexipiprazole
Iloperidone
Perphenazine
Aripiprazole
Risperidone
Inhibitor
Cannabis
Chlorpromazine
Fluphenazine
CYP3A4 subs
CHILL ZAP QB
Cariprazine
Haloperidone
Iloperidone
Lumateperone (avoid with inducers, inhibitors)
Lurasidone
Ziprasidone
Aripiprazole
Pimavanserin
Quetiapine
Brexipiprazole
Haldol & Fluphenazine decanoate
Require bridging with oral therapy
Made with sesame oil
BBW for clozapine
Agranulocytosis
OH, Bradycardia, syncope, cardiac arrest (titrate slowly)
Seizure
Myocarditis, cardiomyopathy
ANC monitoring for normal ANCs (>1500, or >1000 (BEN)) on clozapine
Initiation - 6 months: weekly
6 mo-12 mo: every 2 weeks
> 12 mo: monthly
If >30 day treatment interruption, will restart monitoring
Mild neutropenia on clozapine
ANC 1000-1499
Continue treatment
Monitor ANC 3x weekly until >1500 then resume normal monitoring
Severe neutropenia on clozapine
ANC <500
Stop and do not rechallenge
Monitor ANC daily until >1000 (or >500 for BEN)
Monitor 3x weekly until >1500 (or >baseline for BEN)
Unique side effect from aripiprazole & brexipiprazole
Pathological gambling, other compulsive behavior
Aripiprazole LA-I and overlap
Ability Maintena, Asimtufi: 14 days
Aristada Initio: 1 dose of 30mg
Aristada: if not given with Initio, then needs 21 day overlap
Can you bathe or swim with asenapine patch?
Unknown
But you can shower
Brexipiprazole dose reduction needed when..
CrCl < 60
Moderate hepatic impairment
Antipsychotics CI with severe hepatic impairment
LICAR (b/c liquor is bad for liver)
Lumateperone
Iloperidone
Cariprazine
Asenapine
Risperidone
Cariprazine half life
2-4 days, metabolites have longer
Dose changes may not be clinically seen for a while
Lumateperone unique MOA
-Presynaptic partial agonism for D2
-Postsynaptic antagonism D2
-60x more affinity for Serotonin 2A than D2
-Glutamatergic activity moderator
May be why low incidence of EPS
Lurasidone administration
At least 350kcal of food
Olanzapine-samidorphan
Combination to help mitigate weight gain
Delay for a minimum of 7 days after opioids (14 days if long acting)
Paliperidone LA-I
Establish tolerability with paliperidone first but no bridging required
Must have one-time pretreatment with Sustenna before going to 3-month (Trinza) or 6-month (Hafyera) form
Renal adjustments needed
Brexpiprazole (<60ml/min)
Lurasidone
Paliperidone
Risperidone (<30ml/min)
Risperidone LA-I
Establish tolerability first
Risperdal Consta (IM) requires 3 week bridge with oral risperidone
SC Perseris and Uzedy do not require oral overlap
Ziprasidone administration
Must be taken with 500 calories
Ziprasidone warning
DRESS – can be fatal
Cutaneous skin reactions, eosinophilia, fever
Hepatitis, nephritis, pneumonitis, myocarditis, pericarditis
Treatment initiation
FGA or SGA is reasonable, individualize approach
If has history of use with antipsychotics, can be more aggressive
Older adults with other physical issues may need 1/4-1/2 normal starting dose
Time to effect
2-4 weeks - reassess 2-4 weeks after reaching therapeutic dose
Changing or discontinuing antipsychotics
Gradual discontinuation to avoid withdrawal
Treatment resistant schizophrenia DOC
Clozapine
Adjunctive options
Lamotrigine (add to clozapine if partial response)
Benzos during acute phase
Antidepressants if depressed
Precedex in acute setting for agitation
