Chapter 64 - Schizophrenia Flashcards
Dystonias:
prolonged contraction of muscles during drug initiation, including painful muscle spasms; life-threatening if airway is compromised.
Higher risk with younger males.
Centrally-acting anticholinergics (diphenhydramine, benztropine) can be used for prophylaxis or treatment.
Akathisia:
restlessness with anxiety and an inability to remain still;
treated with benzodiazepinesor propranolol.
Parkinsonism:
looks similar to Parkinson disease, with tremors, abnormal gait and bradykinesia;
treat with anticholinergics or propranolol if tremor is the main symptom.
Tardive dyskinesias(TD):
abnormal facial movements, primarily in the tongue or mouth;
higher risk with elderly females.
TD can be irreversible.
Must stop the drug and replace with an SGA with low EPSrisk (e.g., quetiapine, clozapine).
Dyskinesias:
abnormal movements;
more common with dopamine replacement for Parkinson disease.
Hallucinations:
sensing something that is not present, such as
imaginary voices.
Delusions:
a belief about something real that is not true, such as imagining that your family (which is real) wishes to hurt you (delusion).
Disorganized thinking/behavior:
inability to focus attention and communicate organized thoughts.
DSM-5 DIAGNOSTIC CRITERIA FOR SCHIZOPHRENIA
Note: delusions, hallucinations or disorganized speech must be present
Negative signs and symptoms
- Loss of interest in everyday activities
- Lack of emotion (apathy)
- Inability to plan or carry out activities
- Poor hygiene
- Social withdrawal
- Loss of motivation (avolition)
- Lack of speech (alogia)
Positive signs and symptoms:
- Hallucinations: can be auditory (hearing voices), visual or somatic
- Delusions: beliefs held by the patient that are without a basis in reality
- Disorganized thinking/behavior, incoherent speech, often on unrelated topics, purposeless behavior, or difficulty speaking and organizing thoughts, such as stopping in mid-sentence or jumbling together meaningless words
- Difficulty paying attention
meds/ illicit drugs that can cause psychosis
1- Anticholinergics (centrally-acting, high doses)
2- Dextromethorphan
3- Dopamine or dopamine agonists (e.g.,Requip, Mirapex, Sinemet)
4- Interferons
5- Stimulants, especially if already at risk (includes amphetamines)
6- Systemic steroids (typically with lack of sleep - ICU psychosis)
Illicit substances
1- Bath salts (synthetic cathinones, MDPV)
2- Cannabis
3- Cocaine, especially “crack” cocaine
4- Lysergic acid diethylamide (LSD, hallucinogenics)
5- Methamphetamine, ice, crystal
6- Phencyclidine (PCP)
FGA or SGA as 1st line?
SGAs are used first-line due to a lower incidence of extrapyramidal symptoms (EPS),
yet there are many patients who are stabilized on FGAs and in some initial cases, they may be preferable.
FGAs have a high incidence of EPS, Sx:
- dystonias (muscle contractions),
- dyskinesias (abnormal movements),
- tardive dyskinesias (repetitive, involuntary movements, such as grimacing and eye blinking) and
- akathisia (restlessness, inability to remain still).
Long-Acting Injections:
eliminate the need for daily oral tablets or capsules. They are given IM.
Orally Disintegrating Tablets (ODTs)
are useful with dysphagia (difficulty swallowing) and prevents cheeking (when tablets are hidden inside the cheek and spit out later).
ODTs dissolve quickly in the mouth.
Oral solutions/suspensions
are useful for children and people with a feeding tube (e.g., PEGtube).
Acute IM Injections
provide “stat” relief to calm down an agitated, psychotic patient for their own safety and the safety of others.
IM antipsychotics are often mixed with other drugs (in “cocktails”), such as:
- benzodiazepines for anxiolytic/sedative effects, and
- anticholinergics to reduce dystonias
(e.g., the “Haldolcocktail” contains haloperidol, lorazepam and diphenhydramine).
Can you give Olanzapine and benzodiazepines together?
olanzapine: BBW for sedation/ coma
should not be given together (i.e., in an injection) due to risk of excessive sedation and breathing difficulty.
BBW for antipsychotics and elderly patients with dementia:
Antipsychotics are not indicated for agitation control in elderly with dementia-related psychosis.
There is an increased risk of MORTALITY when used for this purpose, mostly due to CARDIOVASCULAR conditions (e.g., heart failure, sudden death) and INFECTION.
Several antipsychotics also carry a warning for an increased risk of STROKE in patients with dementia. All antipsychotics carry a warning for FALLS.
First-generation antipsychotics (FGAs) work mainly by
blocking dopamine-2 (D2) receptors, with minimal serotonin (5-HT2A)receptor blockade.
low potency FGA:
- chlorpromazine (pro? ma)
- thioridazine (redda mish awiye)
lower potency drugs have inc sedation and lower EPS
mid potency FGA
- loxapine (Adasuve)
- perphenazine (per phenazine)
high potency FGA
- Haloperidol (halo)
- Fluphenazine (ouf awiyye)
- Thiothixene (thick potent)
- Trifluperazine
higher potency drugs have lower sedation and inc EPS
BBW for elderly with dementia related psychosis:
Elderly patients with dementia-related psychosis: i risk death from antipsychotics
BBW QT prolongation drug?
Thioridazine
redda btaamul QT
FGA that cause QT prol
thioridazine, haloperidol, chlorpromazine
FGA that requires REMS and why?
BBW
Adasuve (Loxapine)
causes bronchospasm
Warnings with FGA:
1) Cardiovascular effects:
- QT prolongation (especially with thioridazine, haloperidol, chlorpromazine),
- orthostasis/ falls,
- tachycardia
2) Anticholinergic effects:
- constipation,
- xerostomia,
- blurred vision,
- urinary retention
3) CNS depression
4) Extrapyramidal symptoms (EPS): including
- Parkinsonism,
- dystonic reactions,
- akathisia,
- tardive dyskinesia
(inc EPSwith injections)
- can give anticholinergic (e.g.,benztropine, diphenhydramine) to limit/avoid painful dystonic reactions
5) Hyperprolactinemia:
- infertility,
- oligomenorrhea/amenorrhea (less or no menstrual periods),
- galactorrhea (abnormal breast discharge),
- erectile dysfunction/ dec libido
6) Neuroleptic malignant syndrome (NMS):
- use may be associated with NMS;
- monitor for mental status changes, fever, muscle rigidity, autonomic instability
7) Blood dyscrasias (leukopenia, neutropenia and agranulocytosis),
8) ocular effects
FGA that has metallic taste
Adasuve:dysgeusia(bad,bitter, or metallic taste in mouth)
FGA drugs that can be given as injection? doses?
Haloperidol (Haldol):
- Oral (tablet, solution): start 0.5-2 mg BID-TID,
up to 30 mg/day
- IV: usually 5-lO mg
- Decanoate (monthly): IM only; for conversion from
PO, use 10-20x the PO dose
Fluphenazine:
6 - 12 mg/ day, divided doses
Decanoate: IM every 2 weeks)
Second-generation anti psychotics (SGAs) moa:
block dopamine (D2) and serotonin (5-HT2A) receptors.
…, … and … are unique: they are D2 and 5-HTlA partial agonists, and … is also a 5-HT2A antagonist.
Aripiprazole, brexpiprazole and cariprazine are unique: they are D2 and 5-HTlA partial agonists, and brexpiprazole is also a 5-HT2A antagonist.
Aripiprazole
- brand
- dose
- Abilify
- Abilify Maintena IM suspension
- Aristada injection IM suspension
Tablet, ODT, IM suspension
DOSE:
- 10 - 30 mg PO QAM
- Ability Maintena: lM suspension, give monthly
- Aristada: lM suspension, give every 4-8 weeks
SE:
- Akathisia, activating or sedating,
- headache,
- anxiety,
- constipation
- Lower risk of weight gain,
- some QT prolongation,
- EPS (in children)
1) Drugs that are also used for Tourette syndrome (for tics and vocal outbursts)
2) Drugs that are also approved for irritability associated with autism
- Haloperidol
- Aripiprazole
- Aripiprazole
- Risperidone
What drug do you only give if pt failed to respond to treatment with 2 standard AP treatments, or had significant ADRs?
why?
Clozapine
(must try SGA first)
Clozapine is very effective and has dec risk of EPS/TD, but used no sooner than 3rd line due to severe side effect potential:
- metabolic effects,
- neutropenia
Abrupt D/C of clozapine can cause:
seizure
Clozapine brand names:
Clozapine (Clozaril, Versacloz suspension)
Clozapine dose:
300-900 mg/day, divided
- start at 12.5 mg and titrate;
- titrate off since abrupt discontinuation can cause seizures)
BBW with clozapine:
1) Significant risk of potentially life-threatening neutropenia/agranulocytosis (REMS program)
2) Bradycardia, orthostatic hypotension, syncope and cardiac arrest; risk is highest during the initial titration period especially with rapid dose increases; titrate slowly
3) Myocarditis and cardiomyopathy; discontinue if suspected
4) Seizures, dose related; start at no higher than 12.5 mg once or twice daily, titrate slowly, using divided doses; use with caution in patients at seizure risk (e.g., seizure history, head trauma, alcoholism or taking medications which lower seizure threshold)
SE with clozapine
- Agranulocytosis,
- seizures,
- constipation,
- somnolence,
- metabolic syndrome (inc weight, BG, lipids),
- sialorrhea (hypersalivation),
- hypotension
monitoring with clozapine
- REMS: prescribers and pharmacies must be certified and patients must be enrolled with the Clozapine REMS
- To start treatment, baseline ANC must be
>= 1,500/mm 3 - Check ANC weekly x 6 months,
- then every 2 weeks x 6 months,
- then monthly
- stop therapy if ANC < 1,000/mm 3
patients who smoke can require higher/lower doses of:
- Smoking reduces drug levels
- Clozapine
- Olanzapine
Lurasidone Brand name
Latuda
Lurasidone dose:
40-160 mg/day, divided
Take with food >= 350 kcal
CI with lurasidone
Use with strong CYP450 3A4 inducers and inhibitors is CI
SE with lurasidone
- Somnolence,
- EPS (dystonias),
- nausea,
- risk of metabolic syndrome but nearly weight, lipid and blood glucose neutral
Olanzapine brand name
- Zyprexa,
- Zyprexa Zydis ODT,
- Zyprexa Relprevv injection
Olanzapine+ fluoxetine
brand + indication?
- Symbyax
- for treatment-resistant depression
Olanzapine dose:
10-20 mg QHS
- IM Injection (acute agitation)
-Relprevv inj suspension lasts 2-4 weeks; restricted use
Zyprexa Relprevv BBW:
(Olanzapine)
- Sedation (including coma) and delirium (including agitation, anxiety, confusion, disorientation) have been observed following injection;
- must be administered in a registered healthcare facility and patients are monitored for 3 hours post-injection
- Zyprexa Relprevv REMS program requirements
SE with olanzapine
- Somnolence,
- metabolic syndrome (inc weight, blood glucose, lipids),
- orthostasis
Paliperidone brands
- lnvega
- lnvega Sustenna
- lnvega Trinza
Active metabolite of risperidone; SEs similar
Paliperidone Dose
PO: 3·12 mg daily
- CrCI < 50 ml/min: 3 mg daily
- CrCI < 10 ml/min: Not recommended
OROS delivery enables once daily dosing-do not break or crush
lnvega Sustenna IM injection, give monthly
lnvega Trinza IM injection, give every 3 months (start only after receiving lnvega Sustenna x 4 months)
Paliperidone se
SIDE EFFECTS
- inc prolactin
- sexual dysfunction,
- galactorrhea,
- irregular/missed periods
- EPS, especially at higher doses
- Tachycardia,
- QT prolongation
- Metabolic syndrome (inc weight, blood glucose, lipids)
- Somnolence
which drug can leave a ghost tablet (empty shell) in the stool
Invega (paliperidone)
Quetiapine brand
- Seroquel
- Seraquel XR
Quetiapine dose
400 - 800 mg/day, divided BID or XR qHS
Take XR at night, without food or with a light meal
(< = 300 kcal)
quetiapine se
- Somnolence,
- metabolic syndrome (inc weight, blood glucose, lipids),
- orthostasis,
- possible ocular effects (cataracts)
- Low EPS risk - often used for psychosis in Parkinsons
Risperidone brands
- Risperdal
- Risperdal Consta IM
- Perseris SC
Risperidone dose
2-16 mg/day, divided
- Risperdal Consta: IM injection, give every 2 weeks,
25-50 mg - Perseris: SC injection, monthly
se of risperidone
- inc prolactin
- sexual dysfunction,
- galactorrhea,
- irregular/missed periods
- EPS, especially at higher doses
- Tachycardia, QT prolongation
- Metabolic syndrome (inc weight, blood glucose, lipids)
- Somnolence
Ziprasidone brand
Geodon
ziprasidone dose
40-160 mg/day, divided BID
Take with food
Acute injection: Geodon IM 10 mg Q2H or 20 mg Q4H
Max: 40 mg/day IM
CI & SE of ziprasidone
CI:
QT prolongation; do not use with QT risk
SIDE EFFECTS
Somnolence, EPS, dizziness, nausea
Asenapine
brand
dose
CI
SE
1) Saphris Sublingual tablet
- DOSE: 10-20 mg/day, divided BID
- No food/drink for 10 min after dose
2) Secuado patch
- DOSE: 3.8-7.6 mg applied daily
CONTRAINDICATIONS
Severe hepatic impairment
SIDE EFFECTS
- Somnolence,
- tongue numbness (sublingual tablet),
- EPS (5% more than placebo),
- QT prolongation
Brexpiprazole
Rexulti
2-4 mg daily
SIDE EFFECTS
Weight gain, dyspepsia, diarrhea, akathisia
Cariprazine
Vraylar
1.5-6 mg daily
SIDE EFFECTS
EPS, dystonias, headache, insomnia
lloperidone
Fanapt
12-24 mg/day, divided
Titrate slowly due to orthostasis/ dizziness
SIDE EFFECTS
Dizziness, somnolence, orthostasis, tachycardia
QT prolongation
Lumateperone
Caplyta
42 mg daily
SIDE EFFECTS
Somnolence, EPS
… have variable degrees of metabolic side effects, including weight gain, increased cholesterol, increased triglycerides (TGs) and increased blood glucose (BG).
Drugs with higher metabolic risk should be monitored during treatment and avoided if diabetes or cardiovascular disease is present.
- SGA
Although at a lower incidence than … ,some of the can cause dose-related EPS.
Prolactin levels can increase, causing gynecomastia (painful, swollen breast tissue), galactorrhea, sexual dysfunction and oligomenorrhea/amenorrhea.
FGAs
SGAs
… has the highest efficacy, but has multiple boxed warnings (e.g., …).
It can be tried after failure with at least two other anti psychotics (at least one SGA)
Clozapine
agranulocytosis, seizures, myocarditis
3 things should be assessed to know if a drugs is working well:
1) Patient has had an adequate trial (at least 6 weeks) of an anti psychotic,
2) whether the dose is adequate
3) whether the patient has been taking the medication as prescribed
Can you reuse a drug that didnt work well in the past?
Can you reuse a drug if pt had se to it previously?
If the drug was being taken (at a reasonable dose and for a long-enough trial period) and did not work well, do not use it again.
Do not choose a treatment that was poorly tolerated in the past (e.g., painful dystonia or tardive dyskinesia with haloperidol, painful gynecomastia with paliperidone/risperidone).
Do not choose a QT-prolonging drug like:
- ziprasidone
- haloperidol
- thioridazine
- chlorpromazine
History of movement disorder (e.g., Parkinson disease)
Do not choose a drug with high risk of EPS [e.g., …].
… is preferred.
FGAs, risperidone, paliperidone (at higher doses)
Quetiapine
Overweight/metabolic risk (e.g., inc TG):
Do not choose a drug that worsens metabolic issues like …
There is a lower metabolic risk with …
olanzapine or quetiapine
aripiprazole, ziprasidone, lurasidone and asenapine.
if pt is experiencing Nonadherence or experiencing homelessness:
choose a long acting injection
STAT!
Acute psychosis (and refusing PO meds)
- Haloperidol (Haldol) IV or IM
Sometimes in combination with diphenhydramine and lorazepam
Alternatives:
- Ziprasidone (Geodon) IM
- Olanzapine (Zyprexa) IM
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> Long-acting IM injection
1) Paliperidone (lnvega Trinza): q 3m
2) Aripiprazole lauroxil (Aristada): q 4 - 8 weeks
3) Paliperidone (lnvega Sustenna): 4 weeks
4) Aripiprazole (Abilify Maintena): 4 weeks
5) Haloperidol (Haldol Decanoate): 4 weeks
6) Olanzapine (Zyprexa Relprevv): 2 - 4 weeks
7) Risperidone (Risperdal Consta): 2 weeks
8) Fluphenazine decanoate: 2 weeks
Chronic treatment:
Not adherent to daily PO treatment or swallowing difficulties:
–> other dosage forms:
ODT (not adherent/dysphagia)
1) Aripiprazole (Abilify) ODT
2) Olanzapine (Zyprexa Zydis) ODT
3) Risperidone ODT
Sublingual
1) Asenapine (Saphris)
Oral liquids
1) Aripiprazole (Ability)
2) Fluphenazine
3) Haloperidol
4) Risperidone (Risperdal)
Patch
1) Asenapine (Secuado)
what drugs can u use if failure with 2 or more antipsych:
- Clozapine (Clozaril) tablet
- Versacloz suspension
PSYCHOSIS IN PARKINSON DISEASE
1) quetiapine is used to treat psychosis in Parkinson disease because it has a low risk of causing extrapyramidal effects.
2) Pimavanserin (Nuplazid) is approved for psychosis with Parkinson disease.
- It is an inverse agonist and antagonist at serotonin
5-HT2A receptors and a lesser extent at serotonin
5-HT2Creceptors.
- It does not affect dopamine receptors and does not worsen motor symptoms of Parkinson disease.
Pimavanserin
Nuplazid
Dose: 34 mg PO daily (two 17mg tablets)
WARNINGS
- Not approved for dementia-related psychosis.
- QT prolongation; avoid use with drugs that also increase the QT interval and in patients
with risk factors for prolonged QT interval.
SIDE EFFECTS
Peripheral edema, confusion.
High plasma levels of … and … can increase prolactin and cause EPS.
risperidone
paliperidone
Caution when using … with CYP2D6 inhibitors, like …
risperidone
paroxetine and fluoxetine.
Avoidconcurrent drugs that lower the seizure threshold with …
clozapine
Monitor for respiratory depression and hypotension when antipsychotics are given with …
benzodiazepines
Caution with …, as EPS and TD risk may be increased.
other dopamine blocking agents (e.g., metoclopramide),
counsel: ALL ANTIPSYCHOTIC
Cancause:
o Drowsiness.
o Orthostasis.
O Unusual body movements.
Symptoms include shakiness, stiffness, or uncontrollable movements of the mouth, tongue, cheeks, jaw, arms or legs. Contact your healthcare provider immediately.
Fever, sweating, severe muscle stiffness (rigidity) and confusion. Contact your healthcare provider immediately.
Counsel: Olanzapine, Risperidone, Paliperidone and Quetiapine
■ Can cause hyperglycemia and weight gain.
Counsel Clozapine
■ Can cause low white blood cell count; requires monitoring via REMS program.
Counsel: Risperidone
■ Risperdaloral solution:
- administered directly from the calibrated pipette, or mixed with water, coffee, orange juice or low-fat milk;
- it cannot be mixed with cola or tea.
Counsel Asenapine Sublingual
■ Can cause tongue numbness.
Tardive dyskinesia (TD):
- is a complication that can occur with dopamine receptor blockade, as with anti psychotics.
- can cause irreversible symptoms that include uncontrollable movements in the tongue, face, trunk and extremities and can interfere with walking, talking and breathing.
what are the 2 drugs approved for TD? MOA?
1) Valbenazine
- 1st med approved for TD
2) Deutetrabenazine
MOA:
- reversibly inhibits vesicular monoamine transporter 2 (VMAT2),
- VMAT2: a transporter that regulates monoamine uptake from the cytoplasm to the synaptic vesicle for storage and release.
Valbenazine brand
lngrezza
Valbenazine dose
Start 40 mg PO daily, increase in 1 week to 80 mg PO daily
Moderate-severe hepatic impairment: adjustment required
CYP2D6 poor metabolizer: consider dose reduction
Valbenazine & deutetrabenazine warning
- Somnolence
- QT prolongation (avoid in long QT syndrome)
Deutetrabenazine
brand ?
other indication?
Austedo
Also approved for chorea associated with Huntington’s disease
Deutetrabenazine
Start 6 mg PO BID, increase weekly based on response (max 48 mg/day)
Concurrent strong CYP2D6 inhibitors or CYP2D6 poor metabolizer: max dose 36 mg/day
CI with deutetrabenazine
- Hepatic impairment,
- administration with tetrabenazine or valbenazine,
- administration with an MAO inhibitor (within 14 days)
DDI with VMAT2I
■ Avoid use with MAO inhibitors.
■ Valbenazine and deutetrabenazine are substrates of CYP3A4 and 2D6. Dosereduction is required when given with strong inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin) or 2D6 (e.g., paroxetine, fluoxetine).
■ Valbenazine is a P-gp inhibitor and can increase digoxin concentrations. Dosage adjustment of digoxin may be required.
Neuroleptic malignant syndrome
It occurs most commonly with the FGAs and is due to D2 blockade.
NMS is less common with SGAs and with other dopamine blocking agents, including metoclopramide (Reglan)
NMS onset
The majority of cases occur within two weeks of starting treatment or immediately following high doses of injectables given alongside multiple oral doses.
Occasionally, patients develop NMS after years of antipsychotic use.
NMS signs
NMS is a medical emergency.
- Intense muscle contractions can lead to acute renal injury (due to rhabdomyolysis from the destruction of muscle tissue), suffocation and death.
Signs
■ Hyperthermia (high fever, with profuse sweating)
■ Extreme muscle rigidity (called “lead pipe” rigidity), which
canleadtorespiratory failure
■ Mental status changes
■ Tachycardia, tachypnea and blood pressure changes
Laboratory Results
■ inc creatine phosphokinase and inc white blood cells
ttmt of nms
Treatment
■ Stop the antipsychotic and provide supportive care: cardiorespiratory and hemodynamic support and manage electrolytes
■ Control the patient’s temperature: cooling bed, antipyretics, cooled IV fluids
■ Relaxthe muscles: benzodiazepines, dantrolene (Ryanodex, Dantrium,Revonto)or some cases may require a dopamine agonist (e.g.,bromocriptine)
■ After resolution of the symptoms, consider a different antipsychotic (e.g., quetiapine or clozapine)
