EXAM 5 Schizophrenia Thomason Flashcards
What is the diagnosis criteria for Schizophrenia?
2 or more symptoms of the following for at least 1 month:
-Delusions
-Hallucinations
-Disorganized Speech
-Grossly disorganized/catatonic behavior (unresponsive, staring)
-negative symptoms: blunted, alogia (not talking), abolition (lack of motivation), anhedonia, amotivation
Positive and negative symptoms
Positive:
-Hallucinations
-Delusions
-Disorganized speech
-Grossly disorganized or catatonic behavior
Negative:
-Antipsychotic induced
-Depression
-Extrapyramidal symptoms (EPS, parkinson-like)
-Positive symptoms causing withdrawal
-cognitive symptoms (slow thinking)
-mood symptoms
Which drugs are more effective than others for treating negative symptoms of Schizophrenia?
-Olanzapine (Zyprexa)
-Clozapine
What are Delusions?
!!!
there will be a case to distinguish from hallucinations
False, fixed beliefs
-Delusion of reference (somebody talks about them)
-Religious
-Persecutory
-Gradnios
-Somatic (they believe they have an illness)
-Erotomania
What are Hallucinations?
!!!
Sensory experiences that are not actually present, mostly auditory (speech or sounds)
less common:
visual, olfactory (often brain lesion, check MRI), tactile (feeling bugs or crawling), gustatory
Differentiate other conditions from Schizophrenia
-Schizophreniform: don’t meet the full criteria for Schizophrenia
-Schizoaffective: both, mood disorder and schizophrenia
-major depressive disorder or bipolar disorder with psychotic features -> looks like Schizophrenia
-psychosis due to condition: dementia or high dose of steroids
-substance-induced: marihuana, cocaine, PCP, K2, amphetamine)
Risk factors for developing Schizophrenia
-Perinatal insults (during delivery): hypoxia, fetal distress, influenza, famine (hunger)
-infection or autoimmune causes
-the use of cannabis and amphetamines
-Genetics (10%, 35% if both mom and dad had schizophrenia)
Where does the tuberoinfedibular pathway end?
!!!
Pituitary gland
-when antagonized: prolactin release
RISPERIDONE !!! (also iloperidone)
men get gynecomastia
women (even children) secrete milk
Where does the Nigrostriatal pathway end?
!!!
Basal ganglia
EPS symptoms when antagonized
First gen Antipsychotics block which receptors?
D2 receptors
but also antagonize:
-alpha-1 receptors
-histamine-1 receptors
-msucarainic receptors
What are the side effects of First-gen Antipsychotics?
-QTc prolongation (STOP if greater than 500 ms)
need baseline EKG, then once a year
-Anticholinergic
-Antagonize alpha-2: Orthostatis
-Antagonize Dopamine-2
EPS -> tardive dyskinesia (face, hands)
-dystonia
-akathisia (aunts in the pants)
-parkinsonism
-Hyperprolactinemia, gynecomastia
-sexual dysfunction
-amenorrhea
-osteoporosis
-galactorrhea
Signs of Neuroleptic Malignant Syndrome
can happen with antipsychotics (more often with first-gens)
-muscle rigidity
-hyperthermia
-altered mental status
-autonomic dysfunction
treat with fluids, get the temperature down (cooling blankets, icing)
-dantrolene, benzos (decrease rigidity), amantadine
Which side effect is often seen with fluphenazine or Haloperidol (high-potency antipsychotics)?
Acute dystonic reaction
-tonic contractions of the back, mouth, arms and legs
-young black males most frequently
-early when starting
-give Benadryl or Benztropine (Cogentin)
-prevent by titrating slow
Which drugs can be used for Pseudoparkinsonism?
-Benztropin (Anticholinergic) !!
-Benadryl
-Amantadine
-Pseudoparkinsoism: slowing of voluntary movements after several days or weeks
-often females
What is the best treatment for Akathisia?
Propranolol
-Akathisia - Aunts in their pants, they can’t sit still
-35% incidence -> need to counsel
-seen after 2.5 months
Drug used for tardive dyskinesia
!!!
match the side effect with the treatment
-VMAT-2 inhibitor -> monitor using AIMS
D/C the drug that causes it
-involuntary movements of the face, can be irreversible
-seen after years
-patients may have early EPS signs, genetics involved (their parents had schizophrenia and dyskinesia)
To which receptors do SGAs bind for the most part?
Antagonize
-Dopamine-2 receptors
-5-HT2A receptors
also alpha-2, muscarinic receptors
-all have unique binding profiles -> unique side effects
What are the side effects of SGAs?
-QTc prolongation (especially Ziprasidone and Seroquel) -> use one that has less risk for QTc (like Aripraprazole if it is a concern)
-Tardive dyskinesia - long-term
-Orthostasis for those blocking alpha-2
-Anticholinergic effects:
Urinary retention, constipation, sedation
-Metabolic syndrome
weight gain, diabetes, hyperlipidemia
Which antipsychotic mostly causes weight gain?
Olanzapine (Zyprexa)
Cloazapine
Quetiapine
Olanzapine is used for anorexia bc it stimulates appetite -> weight gain
Antipsychotics with less weight gain
Aripiprazole
Cariprazine
Lumateperone
Ziprasidone
How often should be signs of metabolic syndrome monitored?
at baseline
after 3-4 months
annually
LDL and blood glucose, A1c
weight more often
Which drug is tolerated the most (sedation, less weight gain, orthostatic, QTc)?
Aripiprazole
Which antipsychotics are sedating?
Quetiapine
Olanzapine
Clozapine
Which antipsychotics cause QTc prolongation?
Iloperidone
Ziprasidone
What are the indications of Olanzapine (Zyprexa)?
-Schizophrenia
-Bipolar I
-Depression (combi product with fluoxetine)
-Long-acting injectable (Zyprexa Relprevv)
Indications of Quetipaine
-Schizophrenia
-Bipolar
-Depression
sedation!!, weight gain
How is Quetipaine administered?
-the ER formulation on an empty stomach or light meal (<300 calories) !!
-the IR can be taken with food (IR not seen that often)
Which antipsychotic has a sublingual formulation?
Asenapine
-place under the tongue and allow to dissolve
-don’t eat or drink for at leat 10 minutes after taking it
Side effects of Risperidone
-hyperprolactinemia
-orthostasis (titrate slowly) BID or daily dosing
-EPS (has more D2 antagonism) with higher dosing
-sexual dysfunction
-dose adjust for renal impairment
Which drug is the active metabolite of Risperidone?
Paliperidone (Invega)
-renal dose adjustment
-LAI formulation (Sustenna (1x month)
-counsel on capsule in the stool (OROS formulation) -> since they are paranoid already
AE: increased prolactin levels, EPS
Which antipsychotic has an indication for Schizoaffective disorder?
Paliperidone (Invega)
Schizoaffective disorder: mood disorder + schizophrenia
Which antipsychotic has to be taken with food to ensure absorption?
!!!
Ziprasidone
BID dosing with >500 calories for absorption !!!
-QTc prolongation (10 msec)
Lurasidone -> > 350 calories !!!
Side effects of Iloperidone
-orthostasis (titrate slowly)
-dizziness, dry mouth, fatigue
-hyperprolactinemia!!!
-can have QTc prolongation
->substrate to CYP2D6 and 3A4 (inhibitors increase levels -> QTc)
Indication of Lurasidone
-Bipolar depression !!!
-MDD with mixed features
-Schizophrenia (doesn’t work great for schizophrenia, more often seen for Bipolar depression)
has to be administered with food (>350 calories)
D2 activity: Akathisia, parkinsonism, nausea
Side effects of Aripiprazole
-insomnia (it is activating, some say it is sedative)
-HA
-anxiety
-akathisia -> may be treated with a beta-blocker (propranolol), if D/C the akathisia doesn’t stop for a week due to a long half-life of 75 hr
it is ~weight neutral
CYP2D6 and 3A4 substrate
Which drugs are often associated with the side effects of Akathisia?
-Aripiprazole
-Brexpiprazole
Side effects of Cariprazine
Akathisia
also EPS and Parkinson-like
it is activating: take it in the morning
Disadvantages of LAI
-expensive, often need prior authorization
-less flexible to dose adjustments, patients need to try oral first to see if they tolerate it
-needs time to reach steady state, they need to take oral until it works
-they have to go to the clinic, sometimes pharmacies can administer
-painful injection, injection site rejection
Advantages of LAI
-don’t need to take daily orals
-reduce risk of overdose
-lower risk for rebound symptoms (psychotic - non–psychotic)
-stable steady state
-they see the provider every time they need an injection (can monitor and assess efficacy)
Which antipsychotics have LAI formulations?
First-gens:
-Fluphenazine
-Haloperidol
SGA:
-Risperidone
-Paliperidone (1x monthly Sustenna, 2 injections)
-Aripiprazole (need oral supplementation before it reaches a steady state)
-Olanzapine (post-dose hypotension - monitor for 3h)
Which antipsychotic LAI needs oral supplementation?
!!!
Aripiprazole (Abilify)
Abilify Maintena: 14 days oral
Abilify Asimtufii: 14 days oral
Aristada: 21 days oral or load with 675 mg injection and 30 mg oral
Which LAI has a risk for post-dose hypotension?
Olanzapine
need 3h monitoring
What was the conclusion of CATIE Phase I of the Landmark trial?
they compared Olanzapine with quetiapine, risperidone, ziprasidone, and PERPHENAZINE (1st gen)
-pt stayed longer on Olanzapine - but had more weight gain
-Perphenazine (1st gen) worked as well as the 2nd gens -> since it is 1st gen it is much cheaper BUT it has more EPS side effects
CATIE Phase III
more symptomatic patients (treatment-resistant) chose their antipsychotic drug -> more patients picked clozapine VS combo
Conclusion of the InterSePT trial
Clozapine decreased suicide in schizophrenia
-> it has an FDA-approval for it
FYI: Lithium decreases suicide in bipolar disorder
First-line options for Schizophrenia based on Guidelines
1st: FGA or SGA
2nd: change to another SGA or FGA
3rd: Clozapine for treatment-resistant, need to fail at least 2 antipsychotics
if possible avoid combis of antipsychotics
Indication (role) of Clozapine
-treatment-resistant schizophrenia (failed 2 or more antipsychotics)
-suicidality in patients with schizophrenia or schizoaffective disorder
BBW for Clozapine
-agranulocytosis (high risk in the first 6 months) -MONITORING CBC weekly at the beginning, watch for fever
-Myocarditis (first 8 weeks) - SOB, cardiac symptoms, arrhythmias
-seizures (dose-dependent)
-orthostasis
-need bowel regimen: stool softener, laxatives (don’t use bulking agents - we don’t want bowel infarction)
What tests should be done before starting Clozapine?
-check vital signs: HR and BP
-CBC: WBC and neutrophils count (ANC)
-comprehensive metabolic panel (CMP): Blood glucose
-AIMS: assess tardive dyskinesia
-check EKG, troponin enzymes, C-reactive protein
during therapy check the Clozapine level if they take 100 mg/d (may change the dose based on levels and symptoms)
DDI for Clozapine
!!!
with CYP1A2 inhibitors: decrease the clozapine dose to one-third
with moderate to weak CYP1A2 inh: monitor for side effects
(oral contraceptives, caffeine (competing with Clozapine)
with CYP1A2 inducer: need a higher dose
(cigarettes and cannabis and other inducers like carbamazepine, phenytoin)
Which receptors are targeted by the drug Cobenfy (Xanomeline and trospium chloride)?
NEW DRUG
M1 and M4 receptors, highly expressed in regions associated with schizophrenia
-less EPS and prolactin release since M1 and M4 is less expressed in regions for motor control and hormonal regulation
-avoid in urinary retention, gastric retention, glaucoma, hepatic impairment
Managing using multiple Antipsychotics
-Cross titration: go down with one and up titrate the new antipsychotic
-same in Clozapine augmentation: go down in Clozapine and titrate up the new drug (ex Abilify)
Pregnant women with Schizophrenia
they should continue their meds
-don’t use LAI because we cant dose adjust, use ORAL
-babies may experience EPS, agitation, abnormal muscle tone, difficulty feeding when they are born (since they were exposed)
Which drugs are approved for children?
-Aripiprazole !!!
-lurasidone
-quetiapine
-risperidone (for autistic patients)
-paliperidone
EPS and weight gain are greater than in adults (use weight-neutral meds if possible)
-clozapine may be used for treatment-resistant
Elderly
more delusions and hallucinations
-pick meds with fewer effects on BP
-ALL antipsychotics carry the BBW for increased mortality in elderly with dementia-related symptoms
