Schizophrenia: Overview & Treatment Options

Question 1

Theories on pathophysiology of schizophrenia center on these neurotransmiters

Answer 1

dopamine

serotonin

glutamate

Question 2

In addition to the 3 major neurotramsitters, what other imbalances are the focus of other theories?

Answer 2

aspartate

glycine

GABA

Question 3

Dopamine receptor site most associated with schizophrenia symptoms

Answer 3

D2

Question 4

The Four Dopominergic pathways implicated in schizophrenia

Answer 4

Mesocortical pathway

Nigrostriatal pathway

Mesolimbic pathway

Tuberoinfundibular pathway

Question 5

A decrease or blockade of tuberoinfundibular dopamine results in ________, which in turn results in (3 things).

Answer 5

elevated prolactin levels

galactorrhea, ammenorrhea, and reduced libido.

Question 6

nigrostriatal pathway location in the brain

Answer 6

originates in the substantia nigra and ends in the caudate nucleus.

Question 7

Low dopamine in the nigrostriatal pathway are thought to affect….

Answer 7

the extrapyramidal system, leading to motor problems

Question 8

Mesolimbic pathway location in the brain

Answer 8

extends from the ventral tegmental area to the limbic areas.

Question 9

Mesolimbic pathway plays this role in schizophrenia

Answer 9

an excess of dopamine plays a role in positive symptomology

Question 10

Mesocortical pathway location in the brain

Answer 10

extends from the VTA to the cortex

Question 11

Low mesocortical dopamine levels are thought to cause

Answer 11

Negative symptoms and cognitive deficits in schizophrenia

Question 12

tuberoinfundibular pathway location in the brain

Answer 12

projects from the hypothalamus to the pituitary gland

Question 13

LSD stands for ____ and enhances this neurotransmitter in the brain leading to this new hypothesis for the development of schizophrenia

Answer 13

Lysergic Acid Diethylamide

Serotonin

Serotonin hypothesis

Question 14

Compounds that block both Serotonin and Dopamine are effective in alleviating _____

Answer 14

both the positive and negative symptoms of schizophrenia

Question 15

These two noncompetitive NMDA/glutamate antagonists induce schizophrenia like symptoms.

Answer 15

phenylciclidine & Ketamine

Question 16

Phsyical brain changes in schizoprhenia

Answer 16

Increase in the size of third & lateral ventricles

smaller medial temporal lobe

Question 17

Examples of obstetric complications that increase risk of schizoprhenia

Answer 17

bleeding during pregnancy
gestational diabetes
emergency C-section
asphyxia
low birth weight

Question 18

Fetal disturbances during this trimester increase the risk of schizophrenia by how much? Give two examples linked to the risk increase.

Answer 18

2nd trimester

Double

Infections & excessive stress levels

Question 19

Risk of illness in individuals with genetic relatives

Answer 19

10% for 1st degree relative

3% for 2nd degree relative

Question 20

the risk of one twin having schizophrenia: monozygotic vs dizygotic

Answer 20

48% increase in monozygotic
12-14% dizygotic

Question 21

If both parents have schizophrenia, % risk of having child with illness

Answer 21

40%

Question 22

Environmental stressors linked to schizophrenia

Answer 22

childhood trauma
minority ethnicity
residence in urban area
social isolation

Question 23

Social stressors predisposing individuals to delusional or paranoid thinking

Answer 23

discrimination
economic adversity

Question 24

Prevelance

Answer 24

0.6 - 1.9% in US population

Question 25

First episode onset (males vs women)

Answer 25

Males: early 20's Females: late 20's, early 30's

Question 26

Differential considerations

Answer 26

schizoaffective disorder (or other psychotic disorder) depressive disorder with psychotic features bipolar disorder with psychotic features

Question 27

Positive symptoms

Answer 27

Hallucinations Delusions abnormal motor behaviors

Question 28

Most common negative symptoms

Answer 28

diminished social expression (flattened affect) avolition (decreased initiation of goal-directed behavior)

Question 29

Cognitive symptoms include:

Answer 29

disorganized speech, thought, or attention

Question 30

percentage of patients reporting favorable treatment outcomes

Answer 30

20%

Question 31

Persons with first-episode schizophrenia typically require (lower/higher dose) and are more sensitive to side effects such as _______ & ______________

Answer 31

lower antipsychotic doses weight gain and extrapyramidal symptoms

Question 32

preferred for treatment of first-episode schizophrenia

Answer 32

Second-generation antipsychotics (SGAs)

Question 33

When should First Generation Antipsychotics be included in algorithm stages?

Answer 33

after first episode that include SGAs other than clozapine as options

Question 34

The recommended number of trials of other antipsychotics that should precede a clozapine trial is `

Answer 34

Two

Question 35

earlier use of clozapine should be considered in the presence of

Answer 35

suicidality, comorbid violence, and substance abuse

Question 36

Problem with augmentation agents in response to poor performance on clozapine

Answer 36

Reasonable, yet published results on augmenting agents have not identified replicable positive results

Question 37

Approaches for patients with treatment-resistant schizophrenia who are unable to tolerate clozapine or are not interested in pursuing a trial of clozapine

Answer 37

no benefit from high doses of antipsychotic medication a trial of a different antipsychotic medication may be helpful Augmentation treatment can also be considered,

Question 38

Risk of continuing with high doses of antipsychotic medication

Answer 38

treatment-related side effects are likely to be increased

Question 39

Should a trial of clozapine be delayed by multiple attempts at augmentation therapy?

Answer 39

No, remember the basic algorithm (1st 2 trials of SGA, then try Clozapine, then potential augmentation)

Question 40

Augmentation option for patients with negative symptoms or comorbid depression

Answer 40

Augmentation of antipsychotic therapy with an antidepressant medication

Question 41

Suggested in patients who exhibit catatonia

Answer 41

Use of a benzodiazepine, such as lorazepam

Question 42

Preferred response to if a patient experiences an exacerbation of symptoms while on a stable dose of medication

Answer 42

a reconsideration of the treatment plan is warranted rather than simply adding medications to the existing regimen

Question 43

The identification of treatment-resistant schizophrenia rests on

Answer 43

ONE: a diagnosis of schizophrenia TWO: the persistence of significant symptoms despite adequate pharmacological treatment

Question 44

In identifying treatment-resistant schizophrenia, persistence of the illness is key: define persistence in this context.

Answer 44

symptoms be of at least 12 weeks’ duration in total, be of at least moderate severity, and be associated with at least moderate functional impairment as determined by validated rating scales ! If a prospective medication trial of at least 6 weeks at adequate dose has not led to symptom reduction of more than 20%, this provides additional evidence of treatment resistance !

Question 45

What criteria is needed for an "adequate" trial of medication?

Answer 45

at least two antipsychotic trials should be conducted + with different antipsychotic medications + at least 6 weeks at a therapeutic dosage of medication for each + adherence of at least 80% of prescribed dosages

Question 46

How may one assess adherence to medications?

Answer 46

measure antipsychotic blood level pill counts, dispensing chart reviews, patient/carer reports

Question 47

If there is no significant improvement after several weeks of treatment this impacts the likelihood of substantial improvement how?

Answer 47

The likelihood of substantial improvement (e.g., > 50% improvement in symptoms) is small. Longer trial of a medication may not be warranted

Question 48

A medication trial cannot be viewed as adequate if

Answer 48

Truncated in terms of duration or dosage because of poor tolerability or if limited by poor adherence

Question 49

Because treatment resistance is predicated on adherence to medication, experts suggest a trial of ___________before deciding that a patient’s symptoms are treatment-resistant.

Answer 49

an LAI antipsychotic medication (which reduces the likelihood an adherence issue)

Question 50

Appropriate moments to introduce Clozapine into treatment

Answer 50

After two adequate trials of another anti-psychotic medication After a patient is identified as having treatment-resistant schizophrenia If pt shows response to treatment (>20% reduction in symptoms) yet still have significant symptoms or impairments in functioning [APA believes clozapine is often underused]