Schizophrenia Flashcards
What are the positive sx of schizophrenia?
More common in M or F?
Delusions, Hallucinations, Disorganized thinking, Disorganized speech
Females
What are the negative sx of schizophrenia?
More common in M or F?
Alogia, affective flattening, avolition, anhedonia
Males
What is avolition?
The decrease in the motivation to initiate and perform self-directed purposeful activities.
What is alogia?
Poverty of speech
What is the difference between a bizarre and non-bizarre delusion?
Non-bizarre delusion has element of plausibility;
bizarre delusion is completely implausible.
What’s the lifetime risk of schizophrenia?
What is the prevalence of schizophrenia?
Lifetime risk: 0.05-0.10%
Prevalence: ~1% (recent reviews say 0.55%)
Review the different subtypes of paranoid schizophrenia.
Persecutory 48% Jealousy 11% Mixed 11% Somatic 5% NOS 23%
What’s the most common age-range of onset of schizophrenia.
16-25
schizophrenia.com
Is onset of schizophrenia usually acute or gradual?
Onset may be acute; less common develops gradually
What proportion of schizophrenia cases will go into remission vs. not (lifelong)?
1/3 remission; 2/3 lifelong
What is the DSM-5 criteria for delusional disorder?
– 1 or more delusions, > 1 month
– Schizophrenia Criteria A never met
– Aside from delusion, function not markedly impaired
– If hallucinations, not prominent, related to delusional theme
– If mania/depression, brief relative to delusional periods
(r/o: Substance, Med illness, OCD, Body Dysmorphic Disorder)
What is the tx for delusional disorder?
Antipsychotics
Which of the following require medication tx: hypnogogic and hypnopompic hallucinations, single voice hallucination, and multiple voices hallucinations?
- Hypnogogic and hypnopompic hallucinations do not
require medication treatment - Single voice hallucination and multiple voices hallucinations will typically result in medication treatment
What are the cognitive deficits of schizophrenia?
SMART
- Speed
- Memory (working, visual, verbal)
- Attention
- Reasoning
- Tact (social cognition)
(Pts are moderately to severely impaired compared w/ general population. Appear early in course of illness, persists, and is stable)
What A Criteria symptoms do the “SMART” cognitive deficits of schizophrenia impact?
Disorganized thinking
Disorganized behavior
W/r/t the positive sx of schizophrenia:
- Do they occur early or late in dz?
- Are they correlated with functional improvement?
- Do they respond well to antipsychotics?
– Often when illness is first diagnosed, but actually occurs later in development of illness
– May wax and wane w/ illness exacerbation and improvement
– Correlated w/ hospitalization, but not functional improvement
– Respond well to anti-psychotics
– May stabilize or improve later in life
W/r/t the negative sx of schizophrenia:
- Do they occur early or late in dz?
- Are they correlated with functional improvement?
- Do they respond well to antipsychotics?
– Occur early-prodrome
– May precede psychosis by up to 5-10 years
– Tend to progress w/ course of illness, especially in early years
– Progress most during acute psychotic periods
– Moderately correlated w/ functional improvement
– Fair/poor response to anti-psychotic medication
W/r/t the cognitive sx of schizophrenia:
- Are they correlated with functional improvement?
- When are they first seen?
- Do they respond well to antipsychotics?
– Present from early age
– Moderate progression w/ illness course
– Most progression during episodes of acute psychosis
– Highly correlated w/ functional IMPAIRMENT
– Poor response to anti-psychotic treatment
What is the B Criteria of Schizophrenia?
Social occupational dysfunction
What specifically is referred to in the B criteria of schizophrenia?
Work
What % of schizophrenic patients can’t work or are unemployed?
75%
- Among top 10 common causes of disability
What % of schizophrenics marry?
30-40%
- Most have limited social contacts
What proportion of schizophrenic patients live independently?
1/3
Quality of life a/w schizophrenia ranks among the worst of chronic medical illness
What are the 4 phases of schizophrenia?
- Premorbid (e.g.: 0-10)
- Prodromal (e.g.: 10-20)
- Progression (e.g.: 20-30)
- Stable relapsing (e.g. 30+)
About what % of schizophrenic cases will have a single episode?
Intermittent course?
Chronic course?
Single episode: 12%
Intermittent course: 32%
Chronic course: 56%
(#s estimated from graph)
What is the downward drift hypothesis, w/r/t schizophrenia?
Are the poor at higher risk of schizophrenia?
Downward drift hypothesis says “no, those with
schizophrenia become ‘poor’ due to their social
occupational dysfunction”
What is the prodrome phase of schizophrenia? (give e.g.’s)
Time, several months to years, prior to initial diagnosis where diagnostic criteria not met.
- IoR or magical thinking, but not of delusional intensity
- Impaired perceptions
- Negative symptoms: mood, subjective cognitive decline
- Much of functional decline
What % of schizophrenics have the prodrome phase?
80-85%
Is the presence of a prodrome a positive or negative prognostic sign?
- How does this change the prognosed difficulty of their course of illness?
- Negative
- More likely the patient will have a difficult course of the illness.
What is the time duration criteria for diagnosing schizophrenia? (How much of that time must criteria A be clearly med?)
Schizophreniform disorder?
Brief Reactive psychosis?
Psychosis NOS?
> 6 months*
*with 1 month clearly meeting A criteria
~50% have a (+) or (-) symptom of moderate or greater severity after an adequate med trial.
> 1 month, < 6 months
< 1 month
< 1 month
What is the peak age of onset of schizophrenia in males? Females? Explain.
M: 15-25
F: 25-35
F have 2nd smaller peak after age 40; 3-10%
Which sex is more likely to have schizophrenia?
M=F (actually, M > F but only very slightly)
In working up a patient for schizophrenia, what other diagnosis or groups of diagnoses need to be ruled out?
- Schizoaffective/other psychotic disorders
- Mood disorders
- Medical/Neurological illness
- Substances/Medications
What are the rates of alcohol abuse/dependence in schizophrenia?
Marijuana?
Cocaine?
30-50% alcohol abuse/dependence
15-15% marijuana abuse/dependence
5-10% cocaine abuse/dependence
Autism is __x more common than schizophrenia
10x
What is the baseline risk of having schizophrenia?
~1%
same as prevalence? Before they said lifetime risk was 0.05-0.10%
Risk if your identical twin has schizophrenia?
~50%
Is schizophrenia caused by a single gene?
No
Prenatal and perinatal risks factors for schizophrenia?
– In utero (especially 2nd trimester): Viral infections, Winter births, Starvation, Toxic exposure
– Perinatal anoxia
– Advance paternal age
(all increase risk a small amount)
Overall what factors can contribute to the development of schizophrenia?
Genetic disposition
– Early environmental insults: Prenatal, perinatal,
Neurodevelopmental abnormalities
– Later environmental insults: Subst abuse, psychosocial stressors
Further brain dysfunction
– Periods of psychosis
Neurodegeneration
What is anosognosia?
Lack of awareness one is ill; lack of insight into illness
How does anosognosia affect the care of patients with schizophrenia?
Lack of compliance w/tx recommendations
General population average lifespan is 78. What is the average lifespan for someone with schizophrenia?
(What % shorter than general pop is this?)
48-53 years
30% shorter than general population
What % of schizophrenic pts attempt suicide?
What % complete?
What % of general pop complete suicide?
- 20-40% attempt suicide (BD: 25-40%)
- ~8-10% complete (BD: ~20%!)
- Gen pop ~1% complete
What are the highest risk factors for schizophrenics completing suicide?
- young
- male
- higher functioning
- good insight
- med non-compliance
- past history of violence
- excessive substance use
What % of schizophrenics die of CV dz?
What % of gen pop dies from CV dz?
~75%
~50%
Review the different rates of smoking, diabetes, and obesity in schizophrenics vs. the gen pop.
What are the reasons for this discrepancy?
- smoking 80-90%, gen pop 25%, (2-3x’s more common)
- diabetes 13%, gen pop 3% (2-4x’s more common)
- obesity 42%, gen pop 27% (1.5-2x’s more common)
Reasons for metabolic syndrome:
- poor self care and poor health care (untreated diabetes 30%; untreated HTN 62%; Untreated dyslipidemia 88%)
Review some of the reasons that schizophrenia cost the US economy $63 bil in 2002.
– Illness begins early in life – Significant, long lasting impairment – Heavy demands for hospital care – Ongoing clinical care, rehab, support services – 75% can’t work, on disability
Name some dopamine-agonist drug of abuse that can cause psychosis.
- Cocaine
- Amphetamines
Where is the nigrostriatal tract?
(extrapyramidal pathway) substantia nigra (midbrain) to caudate + putamen of the basal ganglia
Where is the mesolimbic tract?
Midbrain tegmentum to nucleus accumbens and
adjacent limbic structures
Where is the mesocortical tract?
Midbrain tegmentum to anterior cortical areas
Where is the tuberoinfundibular tract?
Arcuate and periventricular nuclei of the hypothalamus to the pituitary
Does the D1 (D1, D5) or D2 (D2, D3, D4) have a higher correlation with antipsychotic activity?
D2
Name some high potency FGAs.
- Haloperidol (Haldol)
- Fluphenazine (Prolixin)
- Perphazine (Trilafon)
- Thiothixine (Navane)
Name some low potency FGAs.
- Chlorpromazine (Thorazine)
- Thioridazine (Mellaril)
- Mesoridazine (Serentil)
__% D2 receptor occupancy is required for efficacy
__% D2 receptor occupancy is correlated with EPS
65% (60?)
80%
*Normal subjects: __% DA receptors occupied at baseline
Schizophrenic subjects: __% DA receptors occupied at baseline
10%
20%
Besides DA, what other NT system dysfunction is linked to schizophrenia?
Glutamate
~__% pts no sig. response to anti-psychotic treatment.
30
What are some EPS side effects?
- Dystonia
- Parkinsonism (TRAP)
- Akathisia
- Tardive dyskinesia
Which dopamingeric pw is blocked to cause EPS side effects?
Nigrostriatal tract
Which dopaminergic pw is blocked to cause an antipsychotic effect?
Mesolimbic tract
Which dopaminergic pw causes negative sx? (theory)
Mesocortical tract
Which dopaminergic pw is blocked to cause endocrine sx? (theory)
Tuberoinfundibular tract
What are some endocrine sx a/w antipsychotics?
- Prolactin elevation
- Galactorrhea
- Gynecomastia
- Menstrual changes
- Sexual dysfunction
*Do positive or negative sx of schizophrenia progress most rapidly during early acute phases of illness?
Negative
*Positive: most common reason for hospitalization
In schizophrenia, how correlated (low/med/high) is functional impairment with cognitive sx?
w/ negative sx?
- High w/cognitive sx
- Med w/negative sx
Review this antipsychotic algorithm for schizophrenia.
• Stage 1: SGA (2nd generation antipsychotic) - Partial or non-response? • Stage 2: different SGA or FGA - Partial or non-response? • Stage 3: Clozapine trial • Stage 4: Clozapine + SGA or FGA • Stage 5: New FGA or SGA • Stage 6: 2 FGA’s, 2 SGA’s or FGA+SGA
In treating schizophrenia, Iif patient does not achieve a __% reduction in symptoms in the first 2 weeks, outcome is likely to be poor at 4 weeks.
25%
- More improvement occurs in the first two weeks than the second two weeks
Schizophrenics having their first episode are more or less susceptible to side effects of meds?
More sensitive (give lower dose)
When are some situations that you might use clozapine?
• Pts with recurrent suicidality or violence
• Pts with substance abuse
• Persistence of positive symptoms
- if > 2 years, consider trial
- if > 5 years, almost have to justify not doing a trial
What are the receptors, other than DA, that are responsible for the side effects of FGAs?
H1 (histamine), M1 (muscarinic), a1 (adrenergic)
receptors
(High risk of Dopamine system side effects)
Which have greater anticholinergic (muscarinic) side effects, low or high potency FGAs?
Low
Which have greater EPS side effects, low or high potency FGAs?
High
Are EPS side effects usually reversible?
Yes (often tx response)
What are some adjunctive meds that can help treat antipsychotic EPS?
- Benztropine, Trihexyphenidyl (anticholinergic)
- Diphenhydramine (antihistamine)
- Amantadine (for dopamine)
Describe tardive dyskinesia.
• Adverse reaction to antipsychotic medications
• Irregular, choreoathetotic movements
- Chorea - irregular, spasmodic movements
- Athetosis - slow writhing movements
• May occur in any muscle group
• Most common in facial, oral, and truncal muscles
Does tardive dyskinesia occur more commonly in older or younger adults?
Younger adults
What’s most common for tardive dyskinesia sx: worsen, remain the same, or improve?
Remain the same
- Spontaneous improvement least common
- About half of patients experience relief of symptoms within 3 months of antipsychotic discontinuation
What are 2 temporary strategies for reducing tardive dyskinesia sx?
*Long-term?
Temporary
- Increase antipsychotic dose temporarily suppresses symptoms
- Benzodiazepine my bring about a modest reduction in symptoms
Long-term
- Reduce antipsychotic dose and time of exposure
- Clozapine
Do SGAs have a greater or lower rate of EPS than FGAs?
Lower rates
Paliperidone/Risperidone > Aripiprazole/Olanzapine/Ziprasidone > Quetiapine/Clozapine
Do SGAs have a greater or lower rate of tardive dyskinesia than FGAs?
Lower rates
High potency > low potency > SGAs
clozapine: none reported
Advantages of high-potency FGAs?
- Haloperidol (Haldol)
- Fluphenazine (Prolixin)
- Perphazine (Trilafon)
- Thiothixine (Navane)
- Injectable formulations (including IV)
- Depot formulations (Haldol + Prolixin)
- Inexpensive
Disadvantages of high-potency FGAs?
- Haloperidol (Haldol)
- Fluphenazine (Prolixin)
- Perphazine (Trilafon)
- Thiothixine (Navane)
• High risk of Dopamine system side effects
- EPS + Tardive Dyskinesia
Advantages of low-potency FGAs?
- Chlorpromazine (Thorazine)
- Thioridazine (Mellaril)
- Mesoridazine (Serentil)
- Highly sedating
- Injectable formulations
- Inexpensive
Disadvantages of low-potency FGAs?
- Chlorpromazine (Thorazine)
- Thioridazine (Mellaril)
- Mesoridazine (Serentil)
- Highly sedating
- Risk of QTc prolongation
- Risk of tardive dyskinesia
In addition to decreasing positive sx of schizophrenia, SGAs also have some effect on these 2 categories of sx:
Negative + cognitive symptoms
[Also beneficial for tx-refractory pts (clozapine only)]
Review some different SGAs (atypicals).
- Aripiprazole (Abilify)
- Risperidone (Risperdal)
- Paliperidone (Invega)
- Ziprasidone (Geodon)
- Asenapine (Saphris)
- Quetiapine (Seroquel)
- Olanzapine (Zyprexa)
- Clozapine (Clozaril) – Second-line use only
What are some unique characteristics of aripiprazole (Abilify)?
(T1/2)
(weight change?)
- Unique pharmacology (partial agonist)
- Disintegrating tablet & injectable formulations
- Long half-life
- 15 mg superior to 30 mg; no advantage to ^ dose
- Minimal risk of metabolic syndrome
What are the unique side effects more commonly seen in risperidone (Risperdol) than in other SGAs?
• Dopamine system side effects
- Dose-dependent EPS + PRL elevation
(also mod risk of weight gain)
Advantages: experience w/ drug, tablet or depot preparations, relatively low cost.
*What are the advantages of paliperidone (Invega)?
• Does not require hepatic metabolism
- 80% renally excreted; *use in pts with liver disease
• Extended-release formulation: Invega Sustenna, monthly
What are the unique side effects more commonly seen in paliperidone (Invega) than in other SGAs?
• Dopamine system side effects
- Dose-dependent EPS + Prolactin elevation
• Mod risk of weight gain
• Avoid if pt has impaired renal clearance capacity
(limited clinical experience)
What are some advantages of using ziprasidone (Geodon)?
- Low risk of weight gain or sexual dysfunction
- Relatively low cost
- Injectable formulation
What are some DISadvantages of using ziprasidone (Geodon)? (*2)
• Twice-daily dosing WITH MEALS
• QTc prolongation
- Avoid if EKG shows qTc >500 milliseconds
- Check pulse. Low pulse risks Torsades. Is pt on a drug that lowers pulse? (eg beta-blocker?)
*What are some advantages to using quetiapine (Seroquel)? (4)
- *Lowest EPS risk
- Sustained Release formulation (once daily)
- Rapid onset of action
- Sedating
What are some disadvantages to using quetiapine (Seroquel)?
- Moderate risk of weight gain
- May cause insomnia
- Longer dose titration
- Moderate-high cost
What are some advantages to using olanzapine (Zyprexa)?
- Extensive clinical experience
- Superior retention in maintenance treatment (CATIE)
- Disintegrating tablet and injectable forms
What are the main disadvantages to using olanzapine (Zyprexa)?
• HIGH risk of weight gain and metabolic syndrome
- ^ triglycerides, ^ lipids, ^ HgbA1C; ^ risk diabetes. 30% pt ^ >7% body weight
• Sedation
• Liver irritation–be cautious in hepatitis pt or of pt on other meds that irritate liver (statins, depakote, carbamazepine, naltrexone)
• High cost
What are some potential disadvantages of asenapine (Saphris), which are still being elucidated?
New drug, many unknowns
• Risk of DA system side effects: EPS + TD, ^ Prolactin, NMS
• Orthostasis, hypotension, syncope, QTc prolongation,
• Weight gain
*What are some advantages to using clozapine (Clozaril)?
• Effective for 30-50% of *tx-refractory pts
- *Suicidal risks, *substance problems
• *Most effective for negative symptoms
• Only proven treatment for TD
*What are some disadvantages to using clozapine (Clozaril)?
- Risk of agranulocytosis
* Unfavorable side effect profile (myocarditis, ^ risk seizures)
Recall: what sx to look for if EPS (D2 blockade)?
- Tremor
- Akinesia/bradykinesia/hypokinesia
- Rigidity (cogwheel)
- Dystonia, akathisia
- Tardive dyskinesia from long-term tx.
- Hyperprolactinemia from lack of D2 inhibition in tuberoinfundibular tract (milk in men, fertility/menses issues in women; osteopenia).
Recall: what sx to look for if anticholingeric (M1 blockade)?
- Can’t see (blurred vision)
- Can’t pee (urinary retention)
- Can’t spit (dry mouth)
- Can’t shit (constipation)
Recall: what sx to look for a1 adrenergic blockade?
Orthostatic hypotension (weakness, dizziness)
Recall: what sx to look if antihistamine (H1 blockade)?
- Sedation
- Weight gain
- (also many others like blurred vision, tinnitus, N/V/D, dry mouth…)
Which FGAs (2) and SGAs (2) are available in depot forms?
- Haloperidol (Haldol) decanoate
- Fluphenazine (Prolixin) decanoate
- Risperidone depot (Risperdal Consta)
- Paliperidone palmitate (Invega Sustenna)
What’s the main advantage of depot formulation of antipsychotics?
Increased compliance
What are some disadvantages of using depot formulations of antipsychotics?
- Decreased flexibility of dosing
- Patient’s don’t accept it
Recall/review the metabolic syndrome effects more a/w SGAs.
“Prevalence of obesity and diabetes in patients with schizophrenia is ___-___ times higher than the general population”
- Weight gain
- Type 2 diabetes
- Elevated LDL cholesterol
- Elevated triglycerides
- Decreased HDL cholesterol
- Diabetic ketoacidosis
“1.5-2.0”x higher than general pop
*Which antipsychotics carry the highest risk of metabolic syndrome?
Which carry the lowest risk?
Highest: Clozapine/Olanzapine/Low Potency FGA Neuroleptics
Lowest: Aripiprazole/Ziprasidone
How would you monitor for metabolic syndrome in a patient on higher risk antipsychotics?
- Personal/family hx
- Weight (BMI)
- Waist circumference
- Blood pressure
- Fasting plasma glucose
- Fasting lipid profile
*The FGA low potency drugs ___________ and ___________ are associated with qTc prolongation and increased risk of cardiac death.
- Thioridazine (Mellaril)
- Mesoridazine (Stelazine)
Does ziprasidone increase risk of sudden cardiac death?
No (just carries a “bold” warning regarding QTc prolongation + associated cardiac risk,)
What is the black box warning seen on all ATYPICAL antipsychotics?
Increased mortality in elderly patients with dementia-related psychosis
(Risk is comparable among all conventional and atypical antipsychotics)
What is the incidence of NMS w/D2 blockade?
0.2% (usually occurs w/in 30 days or sooner)
Besides typical and atypical antipsychotics, what are some other drugs that can cause D2 blockade –> NMS?
- Anti-emetics: prochlorperazine (Compazine)
- Pro-peristaltic agents: metocloperamide (Reglan)
- Anesthetics: droperidol (Innovar)
- Sedatives: promethazine (Phenergan)
Review the actual criteria for dx’ing NMS (name the major sx)
- D2-blockers (no use in past 30 days)
- Hyperthermia (>38C)
- *Muscle rigidity
- 5 of the 9 following sx: ^HR, ^+v BP, ^RR/hypoxia, ^CPK, metabolic acidosis, tremor, incontinence, ^ WBC, diaphoresis/sialorrhea.
- R/O other hyperthermia causes
What is the tx for NMS?
- Stop D2 blocker
- Supportive (fluids, antipyretic, monitoring)
• No consensus on other treatment options
- Lorazepam (Ativan)-useful in reversing catatonia
- Amantadine (Symmetrel)-may release dopamine from terminals
- Bromocriptine (Parlodel)- d2-agonist
- Dantrolene (Dantrium)-causes direct muscle relaxation
- ECT
NMS:
- Mortality rate?
- Recurrence risk w/restarting D2 blocker?
- 5-12% (improving)
- 30% (most can do it w/precautions)
Very generally, what’s a good medication dosing strategy when treating schizophrenia w/antipsychotics?
- Continuous, full-dose antipsychotic treatment is the key to good outcome in schizophrenia
- “Lowest effective dose” strategies are associated with higher relapse rates and poorer outcomes
(weak justifications for using more than 1 antipsychotic drug to treat, but 1/4 get multiple- costly, + additive side effects)
In the CATIE trial, which antipsychotic was shown to have superior patient compliant/retention in maintenance tx?
Olanzapine (Zyprexa)
Which antipsychotic is thought to have the lowest risk of extrapyramidal sx?
Quetiapine (Seroquel)
Which antipsychotic is the only proven tx for tardive dyskinesia?
Clozapine (Clozaril)
Which antipsychotic is thought to be most effective for the negative sx of schizophrenia?
Clozapine (Clozaril)
Which SGAs act more like FGAs when given at high doses (via increased D2 blockade)?
- Risperidone (Risperdol)
- Paliperidone (Invega)
Which antipsychotic must be taken with meals?
Ziprasidone (Geodon)
