Schizophrenia and Other Psychotic Disorders Flashcards
What are some positive symptoms?
- Hallucinations
- Paranoia
- Delusions
- Hostility
- Disorganized speech
- Ideas of reference
What are some negative symptoms?
- Affect
- Alogia
- Avolition
- Asociality
- Anhedonia
Mesolimbic path of dopamine hypothesis
- VTA–>
- nucleus accumbens–>
- D2 blockade–>
- decrease in positive symptoms
Mesocortical path of dopamine hypothesis
- VTA–>
- Prefrontal cortex–>
- D2 blockade–>
- Increase in negative symptoms
Nigrostriatal path of dopamine hypothesis
- SN–>
- Basal ganglia–>
- D2 blockade–>
- Increase in EPS
Tuberoinfundibular path in dopamine hypothesis
- Hypothalamus–>
- Pituitary–>
- D2 blockade
- Increase in prolactin
What are some factors to consider when selecting a treatment?
- Side effect profile
- Past responses to treatment (symptom response and tolerability)
- Physical health conditions that may be affected by medication side effects
- Medication formulations
- Drug-drug interactions
What are the antipsychotic treatment response in hours to days?
- Agitation
- Aggression
- Motor activity
What are the antipsychotic treatment response in 2 to 6 weeks?
- Hallucinations
- Disorganized thinking
What are the antipsychotic treatment response in months or longer?
- Delusions
- Negative symptoms
What are the side effects of serotonin receptor antagonism?
- Reduces EPS
- Possibly improve cognition
- Antidepressant properties
What are the side effects of dopamine-D2 receptor antagonism?
- Therapeutic effect
- Extrapyramidal symptoms
- Hyperprolactinemia
What are the side effects of muscarinic-M1 receptor antagonism?
- Anticholinergic effects (dry mouth)
What are some histamine-H1 receptor antagonism?
- Sedation
- Weight gain
What are the side effects of alpha 1 receptor antagonism?
- Syncope
- Orthostatic hypotension
- Reflex tachycardia
What are some clinical pearls of haloperidol?
-IM:PO 1:2
What are some clinical pearls of fluphenazine?
-IM:PO 1:2
-Oral liquid should be diluted prior to use
What are some clinical pearls of chlorpromazine?
-Weight gain
-Sedation
-IM:PO 1:4
What are some clinical pearls of thiothixene?
- Smoking may reduce levels (CYP1A2 induction)
What are some clinical pearls of thioridazine?
- Highest QTc prolongation risk
What are some clinical pearls of trifluoperazine?
- Smoking may reduce levels (CYP1A2)
What are the long-acting formulations of the first generation antipsychotics?
- Haloperidol
- Fluphenazine
Dystonia
- EPS symptoms
- Within 24-96 hours of initiation
- Involuntary muscle contraction resulting in slow repetitive movements or abnormal postures
What is the presentation of dystonia?
- Facial grimacing
- Involuntary upward eye movement
- Muscle spasms of the tongue, face, neck, and back (back muscle spasms cause trunk to arch forward)
- Laryngeal spasms
What are the risk factors of dystonia?
- High potency antipsychotics
- High antipsychotic dose
- Young men
What are the treatments of dystonia?
- Diphenhydramine 25-50 mg IM/IV
- Benztropine 1-2 mg IM/IV
Akathisia
- EPS symptoms
- Days to weeks
- Inner motor restlessness
What are the presentations of akathisia?
- Restlessness
- Trouble standing still
- Paces the floor
- Feet in constant motion
- Rocking back and forth
What are the risk factors of akathisia?
- fast titration
- middle-aged females
What are the treatment options of akathisia?
- Propranolol 20-120 mg/day
- Anticholinergic agent
- Benzodiazepine
Pseudoparkinsonism
- EPS symptoms
- Days to weeks
- Parkinsonian like symptoms
What are the presentations of Pseudoparkinsonism?
- Stooped posture
- Shuffling gait
- Rigidity
- Bradykinesia
- Tremors at rest
- Pill-rolling motion of the hand
What are some risk factors of pseudoparkinsonism?
- High potency antipsychotics
- High dose
- Older age
- Females
What are some treatment options of pseudoparkinsonism?
- Benztropine 1-6 mg/day or trihexyphenidyl 5-15 mg/day
- Diphenhydramine 35-300 mg/day–> amantadine 100-400 mg/day
Dyskinesia
- EPS symptoms
- Months to years
- Rapid, repetitive involuntary movements
What are some presentations of dyskinesia?
- Protrusion and rolling of the tongue
- Sucking and smacking movement of the lips
- Chewing motion
- Facial dyskinesia
- Involuntary movements of the body and extremities
What are some risk factors of dyskinesia?
- Older age
- Females
- Other EPS especially early onset
- Chemical abuse
- Mood disorders
What are some treatment options of dyskinesia?
VMAT inhibitors, switch to clozapine, pyridoxine 400-1200 mg/day
What are some long acting injections of the second generation antipsychotics?
- Aripiprazole
- Olanzepine
- Paliperidone
- Risperidone
What are some clinical pearls of Quetiapine?
- XL formulation dosed once daily (IR dosed BID to TID)
- XL formulation: < 300 calories
- Sedation (XL formulation may assist)– take at bedtime
What are some clinical pearls of Olanzepine?
- High metabolic risk
- Do not give IM olanzapine within 2-hours of IM lorazepam due to risk of cardiorespiratory depression and excessive sedation
- Smoking (smoke hydrocarbons) induces CYP 1A2 metabolism by ~30%
What are some clinical pearls of Risperidone?
- Strong D2 affinity
- Renal dose adjustments
- CrCl 30-60 mL/min: 75% max dose
- CrCl 10-30 mL/min: 50% max dose
- CrCl < 10 mL/min: 25% of max dose
- Hyperprolactinemia risk (gynecomastia, galactorrhea, amenorrhea, sexual dysfunction)
What are the clinical pearls of paliperidone?
- Active metabolite of risperidone
- Renal dose adjustments
- CrCl 50-80 mL/min: 6 mg/day
- CrCl 10-50 mL/min: 3 mg/day
- CrCl < 10 mL/min: avoid use
- Hyperprolactinemia
- Increased bioavailability when given with food
- Ghost tablet (shell in stool)
What are the clinical pearls of aripiprazole?
- Activating at low doses
- Low risk of weight gain
- Dose adjustments for major CYP3A4/2D6
- May assist in antipsychotic-induced hyperprolactinemia
What are the clinical pearls of brexipiprazole?
- Renal dose adjustment: max 3 mg if CrCl < 60 mL/min
- Dose adjust in moderate/severe hepatic impairment
- Dose adjustments for major CYP3A4/2D6 inhibitors
- Treats in agitation associated with Alzheimer’s dementia
What are the cariprazine?
- Avoid in CrCl < 30 mL/min
- Take with 350 calories
- Dose adjustments for CrCl < 50 mL/min and hepatic impairment
- Low weight gain risk
What are the clinical pearls of ziprasidone?
- Take with 500 calories
- QT prolongation (particularly with IM formulation)
- Low weight gain risk
What are the clinical pearls of iloperidone?
Significant orthostasis – titrate by no more than 4 mg/day
What are the clinical pearls of Pimavanserin?
- Dosing 34 mg/day
- Indication: Parkinson’s Disease
What are the clinical pearls of Asenapine?
- SL tablet: no food/drink for 10 minutes after taking
- Contraindicated in severe hepatic impairment
What are the clinical pearls of Lumateperone?
- Only one dose available (42 mg)
- Take with food
- Dose adjustment in moderate/severe hepatic impairment (max 21 mg/day)
What are criterias for metabolic syndrome:
* Waist circumference
* BP
* Fasting blood glucose
* HDL
* Triglycerides
- Waist circumference:
-M: > 40 inch
-F: >35 inch - BP:
- > or equal to 130/85 - Fasting blood glucose:
- > or equal to 110 mg/dL
- HDL
- M: < 40 mg/dL
- F: < 50 mg/dL
- Triglycerides
- > or equal to 150 mg/dL
What are the black box warnings of clozapine?
- Severe neutropenia (REMS)
- Seizure
- Myocarditis
- Orthostatic hypotension, bradycardia, syncope
- Increased mortality in elderly patients with dementia-related psychosis
What is the starting dose of clozapine?
12.5 mg once or twice daily
How do you monitor clozapine?
- Clozapine level: 350-500 ng/mL
- Clozapine:norclozapine ratio
- Measured as trough
What are some REMS monitoring factors of Clozapine?
- Absolute Neutrophil Count (ANC) ≥ 1500/uL before initiating
- ≥ 1000/uL with benign ethnic neutropenia (BEN)/Duffy-null associated neutrophil count
- Monitoring schedule: Weekly x 6 months; biweekly x 6 months; monthly
Recommendation for mild neutropenia (1000- 1499) in clozapine
- Monitor 3x/week
- Resume normal schedule once ANC > 1500/uL
Recommendation for moderate neutropenia (500-999) in clozapine
- Interrupt therapy
- Daily ANC until > 1000/uL (may resume), then 3x week until ANC ≥ 1500/uL
- Return to previous monitoring interval when ANC > 1500/uL
Recommendation for severe neutropenia (<500) in clozapine
- Interrupt therapy
- Daily ANC until > 1000/uL, then 3x week until ANC ≥ 1500/uL
- Do NOT rechallenge unless prescriber determines benefit outweighs the risks
- If rechallenged, resume treatment as new patient under ‘normal range’ monitoring once ANC ≥ 1500/uL
What are some titration-dependent adverse effects of clozapine?
- Orthostatic
- Tachycardia
- Sedation
- Myocarditis
What is the level/dose-dependent adverse effect?
Seizures
What is the dose-independent adverse effects?
- Sialorrhea
- Constipation
- Urinary incontinence
- Seizures
What is the treatment for sialorrhea?
- Atropine eye drops SL
- Ipratropium nasal spray SL
- Glycopyrrolate, benztropine, clonidine
What is the treatment of constipation?
- Osmotic laxatives (Miralax)
- Stimulant laxatives (Senna)
- Stool softeners (Colace)
What are the symptoms of Neuroleptic Malignant Syndrome (NMS)?
- Fever
- Lead-pipe rigidity
- Mental status changes
- Leukocytosis, elevated creatinine kinase, AST/ALT
How do you manage Neuroleptic Malignant Syndrome?
Discontinue antipsychotic (for at least 2 weeks) –> No other psychotropic during 2-week time period (except benzodiazepines) –> Bromocriptine (Cycloset®) and dantrolene (Dantrium®)
How do you treat psychotic agitation?
- Haloperidol
- Fluphenazine
- Chlorpromazine
- Olanzapine
- Ziprasidone
What are the pros of long-acting injectable antipsychotics (LAIA)?
- Fewer medications to take daily
- Fewer Cmax related events
- Aware of nonadherence
- Longer interventions windows
- Continuous coverage
- Closer follow-up
What are the cons of long-acting injectable antipsychotics?
- Limited dose titration
- Time, logistics, cost
- Fear of needles
- Inability to change course
- Concerns about side effects
Haloperidol
- Schizophrenia
- Dose Frequency: every 4 weeks
- Oral overlap/load:Decrease ½ daily dose every 3 weeks
-NOT required if loaded
Fluphenazine Decanoate (Prolixin)
- Psychotic disorder
- Dose frequency: Every 2-3 weeks
- Dose Overlap/load: decrease 1/2 daily dose every 2 weeks