64. Schizophrenia/Psychosis Flashcards
Common symptoms of schizophrenia
Hallucinations
Delusions
Disorganized thinking/behavior
Schizophrenia pathophysiology is multifactorial and includes altered brain structure and chemistry, primarily involving ___
dopamine, gerotonin, glutamine
DSM-5 dx criteria for schizophrenia
Negative s/sx: lack of emotion (apathy), social withdrawal, loss of motivation (avolition), lack of speech (alogia)
Others: loss of interest in everyday activities, inability to plan or carry out activities, poor hygiene
Positive s/sx: hallucinations, delusions, disorganized thinking/behavior, difficulty paying attention
Drugs that can cause psychotic symptoms
Anticholinergics (centrally-acting, high doses)
Dextromethorphan
Dopamine or dopamine agonists (e.g. Requip. Mirapex, Sinemet)
Interferons
Stimulants, esp if already at risk (includes amphetamines)
Systemic steroids (typically with lack of sleep - ICU psychosis)
Illicit recreational substances: bath salts, cannabis, cocaine (esp “crack”), LSD, methamphetamine, ice, crystal, PCP
Antipsychotics primarily block ___ receptors. Newer antipsychotics also block ___ and other receptors
Dopamin receptors
serotonin
Are positive or negative symptoms of schizophrenia more difficult to treat?
Negative symptoms are more difficult (e.g. lack of motivation, cognitive and functional impairment
What type of antipsychotics are used first-line d/t lower incidence of extrapyramidal symptoms (EPS)?
Second-gen antipsychotics (SGAs)
What type of antipsychotics have higher incidence of EPS, including painful dystonias (muscle contractions), dyskinesias (abnormal movements), tardive dyskinesias (repetitive, involuntary movements, such as grimacing and eye blinking), and akathisia (restlessness)?
First-gen antipsychotics (FGAs)
T/F: Tardive dyskinesia can be irreversible and drug causing TD should be d/c
True
IM antipsychotics are often mixed with other drugs (in “cocktails”), such as ______
BZDs for anxiolytic/sedative effects
Anticholinergics to reduce dystonias
Example: “Haldol cocktail” = haloperidol, lorazepam, and diphenhydramine
Adherence to antipsychotics is poor. What are some formulations that can increase adherence?
Long-acting injections - given IM, less frequent than daily tabs/caps
ODTs - useful with dysphagia and prevents cheeking (when tabs are hidden inside cheek and spit out later)
Oral solutions/suspensions - for children and people with feeding tubs
Acute IM injections - for “stat” relief to calm down agitated, psychotic pt for their own safety and others
Antipsychotics are NOT indicated for agitation control in ___ pts with ___ d/t increased risk of mortality when sued for this purpose (mostly d/t CV conditions)
elderly pts with dementia-related psychosis
Several antipsychotics also carry warning for increased risk of ___ in pts with dementia. All antipsychotics carry a warning for ___
stroke in pts with dementia
Falls
First-gen antipsychotics (FGAs) mainly work by blocking _____ receptors with minimal ___ receptor blockade
dopamine-2 (D2) receptors
Serotonin (5-HT2A) receptors
Many FGAs are in the ___ class; they can be easily recognized with names ending in “-azine”
phenothiazine
Examples of FGAs
High Potency: Haloperidol (Haldol)
Others:
Low potency: chlorpromazine, thioridazine
Mid-potency: loxapine, perphernazine
High potency: fluphenazine, thiothixene, trifluoperazine
What drug class is haloperidol (Haldol)
Butyrophenone
Administration frequency for haloperidol decanoate (Haldol Decanoate)
IM monthly
For vconversion from PO, use 10-20x the PO dose
Administration frequency for fluphenazine decanoate
IM every 2 weeks
Boxed warnings for FGAs
Elderly prts with dementia-related psychosis: increased risk of death from antipsychotics
Thioridazine: QT prolongation
Loxapine inhalation powder (Adasuve): bronchospasm (REMS)
Warnings for FGAs
CV effects: QT prolongation (esp thioridazine, haloperidol, chlorpromazine), orthostasis/falls, tachycardia)
Anticholinergic effects: constipation, xerostomia, blurred vision, urinary retention
CNS depression
Extrapyramidal symptoms (EPS): including Parkinsonism, dystonic reactions, akathisia, tardive dyskinesia (increase EPS with injections)
Hyperprolactinemia: infertility, oligomenorrhea/amenorrhea (less or no menstrual periods), galactorrhea (abnormal breast discharge), ED/less libido
Neuroleptic malignant syndrome (NMS): use may be a/w NMS; monitor for mental status changes, fever, muscle rigidity, autonomic instability
Blood dyscrasias (leukopenia, neutropenia, and agranulocytosis), ocular effects)
Side effects for FGAs
Sedation, dizziness, anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention)
EPS symptoms (Parkinsonism, dystonic reactions, akthisia, tardive dyskinesia): can give anticholintergic (e.g. benztropine, diphenhydramine) to limit/avoid painful dystonic reactions
Others:
Adasuve: dysgeusia (bad, bitter, metallic taste in mouth)
Injections (haloperidol, fluphenazine): injection site pain/redness
Describe a/w Sedation and EPS vs potency of FGAs
Lower potency drugs have increased sedation and decreased EPS
Higher potency drugs have decreased sedation and increased EPS
All cause sedation and EPS
Second gen antipsychotics (SGAs) block ______ receptors
What makes aripiprazole, brexpiprazole, and cariprazine unique?
dopamine (D2) and serotonin (5-HT2A)
D2 and 5-HT1A partial agonists, and brexpiprazole is also a 5-HT2A antagonist
Aripiprazole formulations and dosing frequency
Abilify PO qAM
Abilify Maintena - IM suspension, monthly
Aristada - IM suspension, give every 4-8 weeks
Side effects of aripiprazole
Akathisia, activating or sedating, HA, anxiety, constipation
Lower risk of weight gain, some QT prolongation, EPS (in children)
Clozapine (Clozaril) is very effective and has lower risk of EPS/TD, but used no sooner than 3rd line d/t _____
severe side effect potential (metabolic effects, neutropenia)
Boxed warnings for clozapine (Clozaril)
Sig risk of potentially life-threatening neutropenia/agranulocytosis (REMS)
Myocarditis and cardiomyopathy; d/c if suspected
Seizures (Dose related)
Others: Bradycardia, orthostatic hypotension, syncope and cardiac arrest; risk is highest during initial titration period, esp with rapid dose increases; titrate slowly
Side effect of clozapine (Clozaril)
Agranulocytosis, seizures, constipation, somnolence, metabolic syndrome (increased weight, BG, lipids), sialorrhea (hypersalivation), hypotension
To start clozapine (Clozaril), baseline ANC must be ____. Check ANC weekly x6 months, then every 2 weeks x 6 months, then monthly
Stop therapy if ANC < ___
≥1500
<1000
Examples of second-gen antipsychotics
Aripiprazole (Abilify)
Clozapine (Clozaril)
Lurasidone (Latuda)
Olanzapine (Zyprexa)
Paliperidone (Invega)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Ziprasidone (Geodon)
Lurasidone (Latuda) side effects
Somnolence, EPS (dystonias), nausea
Risk of metabolic syndrome, but lower risk than other SGAs - minimal effect on weight, lipid, and blood glucose
Olanzapine boxed warning
Zyprexa Relprevv: sedation (including coma) and delirium (including agitation, anxiety, confusion, disorientation), must be administered in a registered healthcare facility and monitored 3 hrs post-injection (REMS requirement)
Olanzapine (Zyprexa) side effects
Somnolence, metabolic syndrome (increased weight, BG, lipids), orthostasis
Concern of smoking and olanzapine
smoking reduces drug levels
Paliperidone formulations and dosing frequency
Invega PO daily
Invega Sustenna - IM injection monthly
Invega Trinza - IM injection, every 3 months (start only after receiving Invega Sustenna x4 months)
Invega Hafyera - IM injection give every 6 months (start only after receiving Invega Sustenna x4 months or Invega Trinza x1 dose)
Side effects paliperidone
increased prolactin - sexual dysfunction, galactorrhea, irregular/missed periods
EPS, esp at higher doses
tachycardia, QT prolongation
Metabolic syndrome (increased weight, BG, lipids)
somnolence
Invega can leave ghost tablet in stool (OROS)
Quetiapine (Seroquel) side effects
somnolence, metabolic syndrome (increased weight, BG, lipids), orthosasis, possible ocular effects (cataracts)
Lower EPS risk - often used for psychosis in Parkinson disease
How should quetiapine XR (Seroquel XR) be used?
Take XR at night, without food or with a light meal (≤300kcal)
Risperidone formulations and dosing frequency
Risperdal 2-16mg/day, divided
Risperdal Consta - IM injection every 2 weeks
Perseris - SC injection monthly
Side effects of risperidone (Risperdal)
increased prolactin - sexual dysfunction, galactorrhea, irregular/missed periods
EPS, esp at higher doses
tachycardia, QT prolongation
Metabolic syndrome (increased weight, BG, lipids)
somnolence
How should Ziprasidone (Geodon) be taken
take with food
Contraindications for ziprasidone (Geodon)
QT prolongation - do not use with QT risk
Asenapine (Saphris) formulation and administration notes
Saphris = SL tab
No food or drink after 10 min after dose
Side effect of asenapine (Saphris)
Tongue numbness (SL tab)
Others: Somnolence, EPS (5% more than placebo), QT prolongation
Antipsychotics with higher metabolic risk should be avoided if pt has ____
DM or CV disease
Antipsychotic treatment considerations: Pt has cardiac/QT risk
Do not choose QT-prolonging drug like ziprasidone, haloperidol, thioridzzine, or chlorpromazine
Antipsychotic treatment considerations: Hx of movement disorder (e.g. Parkinson disease)
Do not choose drug with high risk of EPS (e.g. FGAs, risperidone, paliperidone (at high doses)
Quetiapine is preferred
Antipsychotic treatment considerations: Overweight/metabolic risk (e.g. increased TG)
Do not choose a drug taht worsens metabolic issues like olanzapine or quetiapine
Lower metbaolic risk with: aripiprazole, ziprasidone, lurasidone, and asenapine
Antipsychotic treatment considerations: Nonadherence or experiencing homelessness
Choose long-acting injection
Paliperidone (Invega Hafyera) - 6 months
Paliperidone (Invega Trinza) - 3 months
Aripiprazole lauroxil (Aristada) - 4-8 weeks
Paliperidone (Invega Sustenna) - 4 weeks
Aripiprazole (Abilify Maintena) 4 weeks
Haloperidol (HAldol Decanoate) - 4 weeks
Olanzapine (Zyprexa Relprevv) - 2-4 weeks
Risperidone (Risperdal Consta) - 2 weeks
Fluphenazine decanoate - 2 weeks
Antipsychotic treatment considerations: STAT! acute psychosis (and refusing PO meds)
Haloperidol (Haldol) IV or IM - sometimes in combo with diphenhydramine and loraepam
Alt: ziprasidone (Geodon) IM, olanzapine (Zyprexa) IM
Antipsychotic treatment considerations: failure with 2 or more antipsychotics
Clozapine (Clozaril) tab
Versacloz suspension
Antipsychotic treatment considerations: Chronic treatment - not adherent to daily PO treatment or swallowing difficulties
Long-acting IM injection
ODT: aripiprazole (Abilify) ODT, olanzapine (Zyprexa Zydis) ODT, Risperidone ODT
Sublingual : asenapine (Saphris)
Oral liquids: aripiprazole (Abilify), fluphenazine, haloperidol, risperidone (Risperdal)
Patch: asenapine (Secuado)
What 2 antipsychotics are typically used in parkinson disease?
Quetiapine - low risk of EPS
Pimavanserin (Nuplazid) approved for psychosis with Parkinson disease - inverse agonist and antagonist at serotonin 5-HT2A receptors and lesser extent at serotonin 5-HT2C receptors; dose not effect dopamine receptors and dose not worsen motor symptoms of Parkinson disease
T/F: All antipsychotics can prolong QT interval
True
___, a FGA, is a high-risk for QT prolongation
Thioridazine
Smoking can reduce plasma levels of which antipsychotic drugs? (pts who smoke can require higher doses)
olanzapine and clozapine
