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Flashcards in Psychotic disorders Deck (61):
1

Schizophrenia characteristic symptoms

2 of following for >=1 mo
- delusions
- hallucinations
- disorganized thinking/speech
- grossly disorganized/abnormal motor behaviour

Negative symptoms
Social/occupational dysfunction

2

Schizophrenia diagnosis duration

6 mo
with 1 mo of characteristic symptoms

3

Tragedy of schizophrenia

catastrophic illness
tends to persist
10% suicide rate
very common: 0.5-1% of popn
"cancer of mental illness"

4

Complexity of schizophrenia

no single defining feature
multiple characteristic symptoms
symptoms from multiple domains:
- emotion
- personality
- cognition
-motor activity
probably multisystem disorder

5

Negative symptoms of schizophrenia

Alogia
Affective blunting
Avolition
anhedonia

6

Types of hallucinations in psychosis

auditory: common in schizophrenia, but also in alcohol withdrawal
visual: more common in drug-induced psychosis
tactile: more common in cocaine
olfactory: more common in temporal lobe epilepsy

7

Persecutory delusions

theme of being followed/harassed etc
obstructed in pursuit of goals

8

Somatic delusions

that the person has some physical defect/general medical condition

9

Attenuated psychosis syndrome

A: at least 1/3 core psychosis symptoms with relatively intact reality testing, and warrants clincial attention
B: symptoms >=1x/week in past month
C: symptoms began or worsened in past year
D: not better explained by other mental disorder
E: criteria for another psychotic disorder never met

10

Schizophreniform dx

symptoms of schizophrenia
confusion/perplexity
good premorbid functioning
absence of blunted affect
acute onset
>=1 month, but

11

Schizoaffective disorder

Characteristic symptoms of schizophrenia + depressed, manic/mixed episode of mood
Delusions/hallucinations for >=2 weeks in absence of mood symptoms
Combination of schizophrenia + mood disorder
Specifiers: bipolar, depressive

12

Schizoaffective prognosis

better than schizophrenia but worse than mood disorder

13

Schizoaffectve treatment

usually require antipsychotics

14

Delusional disorder diagnosis

non-bizarre delusions (paranoia, infection, deception, or having a disease) >=1 mo
Absence of meeting criteria for schizophrenia
FUnctioning not impaired
subtypes

15

Delusional disorder treatment

poor response

16

Brief psychotic disorder diagnosis

>=1 of:
delusions, hallucinations, disorganized speech ,disorganized behaviour
episode cannot be a culturally sanctioned response/better explained by another mental disorder, substance, or medical condition
often concurrent with severe stressors
>=1 day but

17

Medical conditions that may present with psychosis

temporal lobe epilepsy
tumor
stroke
trauma
endocrine/metabolic abnormalities
infections
MS
AI disease

18

Substance-induced psychotic disorder features

specific onset during intoxication/withdrawal
prominent hallucinations/delusions without insight
evidence symptoms develop during/within 1 mo of substance intoxication or withdrawal

Amphetamines, marijuana, hallucinogens, cocaine

19

Schizotypal personality disorder features

Pervasive pattern of social/itnerpersonal deficits marked by acute discomfort with, and reduced capacity for, close relationsihps
cognitive/perceptual distortions, eccentricities of behaviour
beginning by early adulthood and present in a variety of context, as indicated by >=5 of:
ideas of reference, odd beliefs/magical thinking, unusual perceptual experiences, odd thinking and speech, suspiciousnessor paranoid ideation, inappropriate or constricted affect, behaviour/appearance that is odd, lack of close friends or confidants, excessive social anxiety
Syndrome does not occur exclusively during courseo f schizophrenia, a mood disorder with psychosis, other psychotic disorders, or autism spectrum disorder

20

Major depressive disorder with psychotic features

MDD - >=5 symptoms, 2 week period with functional impairment
cannot be attributable to substance use, other medical conditions, or other psychiatric illnesses including schizoaffective disorder/bipolar disorder

21

Bipolar disorder with psychotic features

Mania - >=1 week with functional impairment
cannot be attributable to substance use, other medical conditions

22

Neurodevelopmental hypothesis of schizophrenia

developmental "insult" occurs during fetal period but is only manifested as psychotic symptoms after puberty
one or more insults may occur in utero, perinatal, childhood, or adolescence
Developmental changes lead to altered brain structure/function

23

Child development - schizophrenia

impairments of motor, cognitive and social function in childhood, years before onset of psychosis
delyaed walking, speech problems and lower scores on school tests

24

Birth complications - schizophrenia

greater number of birth complications than controls
e.g. Rh incompatibility, preeclampsia, low birth weight, hypoxia, gestational diabetes

25

Gross pathology - schizophrenia

enlargement of lateral/3rd ventricles
ventricular size: vary widely, only larger in some patients, increased in other situations
small reduction in total brain weight - more pronounced in temporal lobe (hippocampus) and frontal, correlates with poor function during life
pathology present at onset of illness

26

Microscopic pathology - schizophrenia

alteration in position of neurons
abnormal cell migration during critical period of prenatal brain development
- cerebral cortex forms improperly --> aberrant connections and abnormal NT
Symptoms evolve over course of illness
brain tissue loss over time greater in schizophrenia, highest close to disease onset
decreased brain volume may reflect a reduction in amount of neuropil
size/complexity of neuronal dendrites reduced
- neurons slightly smaller
- dendritic spines reduced
Abnormal amount or function of synaptic proteins

27

Dopamine hypothesis in psychosis (primary)

Drugs that Decrease DA --> alleviate psychosis
- antipsychotics (antagonist at DAD2), clinical effectiveness related to D2 receptor affinity

Drugs that Increase DA can cause psychosis
- L-dopa in PD
- illicit drugs

28

Limitations of dopamine hypothesis (primary) in psychosis

explains positive but NOT negative symptoms/cognitive impairment
negative/cognitive symptoms not well-controlled by typical antipsychotics; not brought on by use of cocaine/amphetamine

29

Revised dopamine hypothesis

Imbalance in brain DA
Increased DA in subcortical regions (nucleus accumbens) --> positive symptoms
Decreased Da in prefrontal cortex --> negative symptoms, cognitive deficit
Increased DA synthesis capacity/release in respones to amphetamine in striatal regions
Distinct regional distribution of dopamine receptors
Decreased dopamine activity in the PFC --> increased DA activity in striatal regions
Increased striatal dopamine transmission associated with psychosis
DA not only NT involved
- antipsychotics do not only bind at DA receptors
- substances that act on other NT systems can also produce psychosis

30

Dopamine at the synapse

Antipsychotics: block D2 receptor post-synaptic
Cocaine: block reuptake
Amphetamines: reversal of reuptake
increase level of DA from presynaptic membrane
decrease MAO breakdown

31

Nigro-striatal pathway

role in control of voluntary movement as the part of the extrapyramidal system
antipsychotic blockade at D2 may precipitate EPS

32

Mesolimbic pathway

VTA-nucleus accumbens
emotion/reward
posotive symptoms

33

Mesocortical pathway

VTA - PFC
motivation/cognition
negative symptoms

34

Tuberoinfundibular pathway

Hypothalamus - pit
DA inhibits prolactin release
antipsychotic may lead to galactorrhea, amenorrhea, sexual dysfunction

35

Schizophrenia/Glutamate

schizophrenia associated with NMDA receptor hypofunction
Phencyclidine (PCP) and ketamine - NMDA antagonists; can mimic positive/negative symptoms, exacerbate symptoms
ubiquitously distributed in CNS
can determine dopamine release, leading to changes in DA transmission similar to those seen in schizophrenia

36

Serotonin - schizophrenia

hypothesis suggests psychosis could result from increased 5HT transmission
LSD: can produce psychosis - mimic serotonin; act through 5HT2A
some atypical antipsychotics also act at 5HT2A
serotonin system also regulates dopaminergic tone

37

Other pathophysiological causes of schizophrenia

GABAergic interneurons - direct influence on glutamatergic regulation of dopamine
cholinergic system - disruption in DA balance?

38

MOA of 1st generation antipsychotics

D2 mesolimbic: antipsychotic
D2 mesocortical: neuroleptic-induced deficit syndrome - increase negative symptoms
D2 nigrostriatal: EPS
D2 tuberoinfundibular - increase PRL

blockage of D2 at all pathways

39

Side effects of 1st gen antipsychotics

H1: sedation, weight gain
alpha1: decreased BP, dizziness, drowsiness
M1: dry mouth, urinary retention, blurred vision, constipation

40

1st gen antipsychotic - low affinity

Chlorpromazine
SE related to H1, alpha1, M1 receptor antagonism - sedation, weight gain, orthostatic hypotension, urinary retention

41

1st gen antipsychotic - high affinity

Haloperidol
pimozide
perphenazine
SE related to D2 antagonism - EPS

42

1st generation antipsychotic characteristics

D2 antagonist
neuroleptic induced deficit syndrome
EPS
increase in prolactin

43

2nd generation antipsychotic characteristics

D2 antagonist + 5HT2A antagonist
REDUCED:
- neuroleptic induced deficit syndrome
- EPS
- prolactin

44

2nd gen antipsychotic examples

Clozapine
aripirazole
- pines
-idones
long-acting injectibles

45

Usage of 1st vs 2nd gen antipsychotics

no clear/consistent difference between 1st gen/2nd gen agents with regards to treatment respones to positive symptoms with exception of clozapine for tx-resistant patients
2nd gen maybe better than 1st gen for negative symptoms
2nd gen have greater propensity to cause metabolic side effects (weight gain, DM, dyslipidemia, metabolic syndrome)

46

EPS symptomatic treatment

due to decrease dopaminergic, increased cholinergic transmission
M1 pharmacological treatment: anticholinergic - benztropine, trihexphenidyl

note: some antipsychotics have potent anticholinergic effects --> inherent protection against EPS

47

5HT1A antagonism

antidepressant
anxiolytic
reduces EPS, negative symptoms

48

5HT2A antagonism

reduces EPS, potentially reduces negative symptoms

49

Psychosis treatment guidelines

1) Trial of a single atypical (2 weeks)
2) trial of a different atypical )
3) trial of a single atypical or conventional OR
trial of clozapine
4) augmentation clozapine + Li, anticonvulsants, antidepressants, ECT
5) combination Atypical+ atypical or atypical + conventional

50

Changing antipsychotics

threshold for deciding to change antipsychotic due to side effects should be low
some can be treated with adjunctive medication
some decrease with time (wait 4-6 weeks if patient is benefitting from medication)
multiple medications could cause side effects

51

Tx of acute dystonia (antipsychotic)

prevalence: 10%; more common in young males, neuroleptic naive and with high potency antipsychotics
can occur within hours of starting antipsychotics
patient may not be able to swallow - can give iv, im

Tx: anticholinergic
benztropine
dipenhydramine

52

Tx of pseudo-Parkisonism (antipsychotic)

prevalence: ~20%
more common in elder females and those with pre-existing neurological damage
can occur days - wks after antipsychotic started/increased

Tx: reduce dose of antipsychotic
change antipsychotic
treat with oral anticholinergic - monitor q 3 mo
don't prescribe at night since symptoms are absent during sleep

53

Tx of akathisia due to antipsychotics

prevalence ~25%
less with atypicals
occurs within hours - wks of starting/increasing dose
internal dysphoric restlessness

Tx: reduce dose of antipsychotic
propranolol
benzodiazepine
can use propranolol + benzo

54

Tx of tardive dyskinesia due to antipsychotics

Prevalence: ~5%/y of antipsychotic exposure
moe common in elderly women, those with affective illness and those that develop EPS
occurs mo-yrs, 50% reversible
repetitive purposeless movements that worsen under stress
stop anticholinergic if prescribed

Tx: reduce dose of antipsychotic
change to atypical antipsychotic
switch to clozapine/quetiapine

55

Tx of neuroleptic malignant syndrome due to antipsychotics

risk factors: young male, neurologic disabilities, dehydration, exhaustion, agitation, rapid/parenteral administration of AP
reported with all antipsychotics
sympathetic hyperactivity due to dopaminergic antagonism + psychological stressors
muslce rigidity, confusion, fluctuating LOC, diaphoresis, fever, hyperthermia, fluctuating BP, tachycardia

Tx: d/c antipsychotic
bromocriptine (D2 agonist) + Dantroline (muscle relaxant)
amantidine (D2 agonist)

56

Tx mild sedation + psychosis

lorazepam +/- risperidone, olanzepine, or quetiapine

57

Tx moderate sedation + psychosis

Lorazepam + loxapine / haloperidol
(lorazepam + haloperidol reduces incidence of EPS)
Haloperidol + antihistamine
Olanzepine im

58

Tx extended period of sedation + psychosis

Zuclopenthixol acetate
not for those who are naive to antipsychotics

59

Tx insomnia in the context of psychosis

benzodiazepine
zopiclone
trazodone
prn

prn for insomnia should be time-limited

60

Tx persistent symptoms of aggression/hostility/mood liability

mood stabilizer (valproic acid, lithium, carbamazepine)
if partial/non-response, use clozapine

Clozapine can increase the risk of seizures at high doses

61

Tx depression in schizophrenia

not in acute phase

SSRI, venlafaxine XR, buproprion SR, mirtazapine
use another if partial/non-responsive

depression/suicide common in schizophrenia
some antidepressants can cause akathisia