1
Q
When does Schizophrenia typically take effect?
A
late adolescence
Males: 15-24 years old
Females: 24-35 years old
2
Q
What is the dysregulation hypothesis?
A
Dopamine blocking properties to treat positive sx
3
Q
With which types of symptoms might a patient with Schizophrenia present?
A
- positive symptoms: “added on”
- negative symptoms: “taken away”
- cognitive symptoms
4
Q
What are some positive symptoms?
A
psychotic or affective | “added on”
- hallucinations
- sensory (auditory, visual, tactile, olfactory, gustatory)
- delusions (fixed, false beliefs)
- thoughts/ speech disorders: (tangential, disorganized, circumstantial)
“thought blocking”, “word salad” - movement disorders (agitated, catatonic)
5
Q
What are some negative symptoms?
A
affective | “taken away”
- social withdrawal
- diminished emotional expression, speech, and thought
- depressive sx
- poor self-care
- sleep/appetite disturbances
6
Q
Secondary causes of negative sx:
A
- medications
- mood disorders
- social issues
7
Q
What are the cognitive symptoms?
A
deficiencies in:
- attention
- processing
- verbal/visual memory
- working memory
- problem solving
8
Q
What are the likely causes of schizophrenia?
A
- genetic
- altered brain chemistry
- ?
9
Q
Comorbid medical illnesses:
A
- T2DM
- COPD
- obesity
- poor diet
- poor sleep
- tobacco abuse
- drug/ETOH use
10
Q
Comorbid psychosocial issues:
A
- poor hygiene
- impaired self-care
- difficulty living independently
- difficulty forming relationships
- difficulty providing for themselves/ maintaining employment
- isolation
11
Q
What is a comprehensive assessment?
When do we use it?
A
- physical/neurological exam
- history
- Labs:
- BMP
- UA
- LFTs
- Thyroid profile
- serum pregnancy
- syphilis serology
- urine (for toxicology)
This is to rule out other conditions with similar presentations
Patients with symptoms of psychosis should be treated with antipsychotic monotherapy (APM)
- depression/anxiety should also be treated if indicated
12
Q
Nonpharmacologic therapy:
A
- psychosocial interventions*
- social skills training
- CBT
- cognitive remediation
13
Q
What do we need to do/remember when a patient’s symptoms have improved?
A
continue treatment with the SAME antipsychotic medication
this should never be switched if they are stable (insurance formularies should not change and affect this)
14
Q
What did the CATIE trial reveal about SGA?
A
SGA may be more effective for:
- relapse prevention
- affective/negative sx
- cognitive function
15
Q
Adverse Effects | FGA
A
- sedation
- EPS
- tardive dyskinesia (repetitive, involuntary movements)
16
Q
Adverse Effects | SGA
A
- QTC prolongation
- Metabolic effects
- weight gain
- incr. blood sugar
- DLP
- incr. risk for DM
17
Q
Which FGA are most likely to cause EPS?
A
Fluphenazine & Haloperidol (high risk)
trifluoperazine, thiothixene, perphenazine, loxapine (moderate)
18
Q
Which FGA are most likely to cause sedation?
A
chlorpromazine & thioridazine (high risk)
loxapine (moderate)
19
Q
Which FGA are most likely to cause anticholinergic side effects?
A
thioridazine > chlorpromazine
20
Q
Which FGA are most likely to cause CV side effects?
A
chlorpromazine & thioridazine (high risk)
loxapine (moderate)
21
Q
Which FGA are most likely to cause seizure/QTc prolongation?
A
THIORIDAZINE
22
Q
EPS: Acute Dystonia
- Time of onset
- Risk factors
- S&S
- Management
A
- 24-96 hours (1-4 d) after starting or increasing dose
- young males & high potency FGA
- muscle spasms (abnorm position or spasm of head, neck, limb, and trunk muscles)
- IM diphenhydramine or benztropine
*treat immediately and aggressively
23
Q
EPS: Akathisia
- Time of onset
- Risk factors
- S&S
- Management
A
- within months
- young pts & high potency FGA
- inner restlessness, rocking, tapping, inability to sit for long periods (“ants in your pants”)
- reduce dose OR switch to another antipsychotic
(then anticholinergics (benztropine), beta-blockers (propanolol), BZD)
24
Q
EPS: Pseudo-Parkinsonism
- Time of onset
- Risk factors
- S&S
- Management
A
- 1-2 weeks (higher % in elderly)
- older pts, females, higher doses, depressive sx
- presents like Parkinson’s (stooped posture, tremors, slowed movements, stiffness, mask-like facial expressions)
- Anticholinergics/antiparkinson’s agents OR decrease dose vs change drug
*this is NOT parkinsons, and is likely caused by the medications
25
EPS: Tardive Dyskinesia
1. Time of onset
2. Risk factors
3. S&S
4. Management
1. 3+ mo of tx
2. older pts, females, African Americans, longer duration of tx, PMH of EPS, substance abuse, mood disorders, DM
3. Choreiform & Athetoid Movements (lip smacking, tongue protrusions, grimacing)
4. STOP tx & switch to another antipsychotic
(consider VMAT2, valbenazine, deutetrabenazine)
* sx may get worse initially after switch
26
What are Choreiform movements?
rapid, objectively purposeless, irregular, spontaneous
27
What are Athetoid movements?
slow, irregular movements in face, neck, trunk, extremities
28
What is Neuroleptic Malignant Syndrome (NMS)?
life-threatening idiosyncratic reaction to antipsychotic drugs (FGA/SGA)
29
What are the sx of NMS?
How is it treated?
sx:
- fever
- mental status changes
- muscle rigidity
- autonomic stability
tx: supportive care, bromocriptine, dantrolene
* recognition and supportive tx are the MOST important
30
What SGA are most likely to cause anticholinergic SE?
clozapine (SVR)
olanzapine (mod)
31
What SGA are most likely to cause EPS?
Aripiprazole Brexpiprazole (SVR)
Risperidone, paliperidone, cariprazine (mod)
32
What SGA are most likely to cause orthostatic HOTN?
clozapine (SVR)
risperidone, paliperidone, quetiapine, lioperidone
33
What SGA are most likely to cause incr. prolactin?
risperidone, paliperidone (SVR)
34
What SGA are most likely to cause QTc prolongation?
quetiapine, ziprasidone, iloperidone
35
What SGA are most likely to cause sedation?
clozapine, quetiapine (SVR)
Iloperidone (mod)
36
What SGA are most likely to cause wt gain?
clozapine & olanzapine (SVR)
risperidone, paliperidone (mod)
37
What SGA are most likely to cause incr. glucose?
clozapine & olanzapine (mod)
38
What SGA are most likely to cause incr. lipids?
clozapine & olanzapine (SVR)
quetiapine (mod)
39
How do we monitor EPS?
Abnormal Involuntary Movement Scale (AIMs)
--> evaluate pt for any EPS sx when on APM
* ideally it would be the same person evaluating the same patient at the same time
40
What are common AE with risperidone or paliperidone tx?
- higher doses increase incidence of EPS
- hyperprolactinemia
- amenorrhea
- galactorrhea
- gynecomastia
41
Risk factors for QTc prolongation:
- congenital QT syndrome
- arrhythmias
- DM
- female gender
- hypoK
- hypoMg
- hyperNa
42
What are the inhibitors & inducers of CYP1A2?
inhibitor: fluvoxamine
inducer: cigarette smoking
43
What are the inhibitors & inducers of CYP2D6?
inhibitors: fluoxetine, paroxetine, sertraline, bupropion
inducer: CBZ
44
What are the inhibitors & inducers of CYP3A4?
inhibitors: erythromycin, some antifungals, protease inhibitors
inducers: barbiturates, phenytoin, rifampin, CBZ, glucocorticoids
45
What are the LAI FGAs?
What are the pros & cons?
- Haloperidol decanoate
- Fluphenazine decanoate
pro: less expensive
con: high potency...EPS more likely
46
What are the LAI SGAs?
What are the pros & cons?
- Zyprexa Relprevv
- Risperidal Consta
- Abilify maintena
- Aristada
- Aristada Initio
- Invega Trinza
Pros: improved adherence, less SE (even serum [ ]s)
Cons: must be administered in clinic or pharmacy (adherence issues), none of these are generically available...so EX$PEN$IVE
* we should remember these pts are typically paranoid, and not very adherent
47
Tx: adolescents
1. intensive & comprehensive highly structured environments that include special ed and psycho-ed
2. SGA if psychotic sx cause impairment or interfere
abilify, zyprexa, risperidal, invega
48
Most common SE from tx in children?
EPS, wt gain
49
Concerning SE from tx in kids?
- sedation
| - anticholinergic effects (effect school performance)
50
Tx: elderly
START low and GO sloooooooow
- more vulnerable to SE
BBW: increased motality if dementia + APM
(weigh risk v benefit: may want to keep them at home and treat instead of hiring an aid or moving them to a care facility)
51
Tx: substance dependence/abuse
- poorer response to FGA
- more EPS in pts abusing substances
- more likely for NONADHERENCE
* make sure mental health illness AND substance abuse are treated
52
Tx: resistant pts
persistent (+) sx despite tx with 2+ different APM given at adequate doses for 4-6 wks
- CLOZAPINE (alone or in combo)
(may also augment with FGA, SGA, mood stabilizer, or ECT)
53
Key notes: Clozapine
treatment-resistant schizophrenia: after 2 failed tx of antipsychotic monotherapy OR severe sx + suicidality
- (also approved for treating aggression and suicidality)
BBW: agranulocytosis, myocarditis, cardiomyopathy, mitral valve incompetence, seizures
54
Clozapine SE
- orthostatic HOTN
- bradycardia
- syncope
- sedation
- enuresis
- anticholinergic effects
- metabolic syndrome
- hyper-salivation (...lovely)
55
Tx: acute psychotic pts
pharmacologic + psychological intervention
- IM SGA +/- IM Lorazepam
(geodon, abilify, zyprexa)
SGA preferred, but FGA (haloperidol) is acceptable
*these are the cases where the police are called and the pt is brought to the ER (danger to themselves or others), likely sedated to get them more manageable
56
Tx: Pregnancy & Lactation
high potency FGA
(APM usually continued if risk of relapse is more detrimental to both baby and mother)
if APM tx continued:
- limb defects, dyskinesias
- risk for EPS & withdrawal in newborns (3rd TRIMESTER)
relapse: increases stress on infant and increases risk of complications (growth abnormalities & disabilities)
57
Do high or low potency FGA if used in pregnancy have a higher risk of limb defects & dyskinesias?
low potency FGA = higher risk
58
Schizophrenia + pregnancy have an increased risk of:
- stillbirth
- infant death
- preterm delivery
- low birth weight
- small for gestational age
lack of prenatal care; higher rates of smoking while pregnant :(((
59
Which drugs do we actually want to use in pregnancy & lactation?
Clozapine & lurasidone (B)
higher potency FGAs (and all others lol) (C)
60
Metabolic syndrome
3+ of the following:
- waist circumference (M > 40 in | F > 35 in)
- HDL (M < 40 mg/dL | F < 35 mg/dL)
- TGLs 150+ mg/dL (or on meds)
- BP > 130/85 (or on meds)
- FBG > 100 mg/dL (or on meds)
61
Medication classes causing: QTc prolongation
- antiarrhythmic agents
- FGAs
- antibiotics
- antidepressants
62
Medication classes causing: sedation
- sleep aids
- antihistamines
- pain meds
- antidepressants
- anticonvulsants
- BZDs
63
Medication classes causing: HOTN
- antihypertensives
- pn meds
- antidepressants
- BZDs
64
Medication classes causing: anticholinergic effects
- anticholinergics
- antihistamines
- antidepressants
65
Medication classes causing: wt gain/ metabolic abnormalities
- antidepressants
| - anticonvulsants
66
ANC Level & Tx recommendation
1500+/uL ---> required for tx initiation
<500/uL ---> interrupt tx, don't restart unless benefits outweigh risk (severe neutropenia)
