Psychotic disorders Flashcards
Schizophrenia characteristic symptoms
2 of following for >=1 mo
- delusions
- hallucinations
- disorganized thinking/speech
- grossly disorganized/abnormal motor behaviour
Negative symptoms
Social/occupational dysfunction
Schizophrenia diagnosis duration
6 mo
with 1 mo of characteristic symptoms
Tragedy of schizophrenia
catastrophic illness tends to persist 10% suicide rate very common: 0.5-1% of popn "cancer of mental illness"
Complexity of schizophrenia
no single defining feature multiple characteristic symptoms symptoms from multiple domains: - emotion - personality - cognition -motor activity probably multisystem disorder
Negative symptoms of schizophrenia
Alogia
Affective blunting
Avolition
anhedonia
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
Persecutory delusions
theme of being followed/harassed etc
obstructed in pursuit of goals
Somatic delusions
that the person has some physical defect/general medical condition
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
Schizophreniform dx
symptoms of schizophrenia confusion/perplexity good premorbid functioning absence of blunted affect acute onset >=1 month, but
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
Schizoaffective prognosis
better than schizophrenia but worse than mood disorder
Schizoaffectve treatment
usually require antipsychotics
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
Delusional disorder treatment
poor response
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
Medical conditions that may present with psychosis
temporal lobe epilepsy tumor stroke trauma endocrine/metabolic abnormalities infections MS AI disease
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
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
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
Bipolar disorder with psychotic features
Mania - >=1 week with functional impairment
cannot be attributable to substance use, other medical conditions
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
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
Birth complications - schizophrenia
greater number of birth complications than controls
e.g. Rh incompatibility, preeclampsia, low birth weight, hypoxia, gestational diabetes
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
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
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
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
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
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
Nigro-striatal pathway
role in control of voluntary movement as the part of the extrapyramidal system
antipsychotic blockade at D2 may precipitate EPS
Mesolimbic pathway
VTA-nucleus accumbens
emotion/reward
posotive symptoms
Mesocortical pathway
VTA - PFC
motivation/cognition
negative symptoms
Tuberoinfundibular pathway
Hypothalamus - pit
DA inhibits prolactin release
antipsychotic may lead to galactorrhea, amenorrhea, sexual dysfunction
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
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
Other pathophysiological causes of schizophrenia
GABAergic interneurons - direct influence on glutamatergic regulation of dopamine
cholinergic system - disruption in DA balance?
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
Side effects of 1st gen antipsychotics
H1: sedation, weight gain
alpha1: decreased BP, dizziness, drowsiness
M1: dry mouth, urinary retention, blurred vision, constipation
1st gen antipsychotic - low affinity
Chlorpromazine
SE related to H1, alpha1, M1 receptor antagonism - sedation, weight gain, orthostatic hypotension, urinary retention
1st gen antipsychotic - high affinity
Haloperidol
pimozide
perphenazine
SE related to D2 antagonism - EPS
1st generation antipsychotic characteristics
D2 antagonist
neuroleptic induced deficit syndrome
EPS
increase in prolactin
2nd generation antipsychotic characteristics
D2 antagonist + 5HT2A antagonist REDUCED: - neuroleptic induced deficit syndrome - EPS - prolactin
2nd gen antipsychotic examples
Clozapine aripirazole - pines -idones long-acting injectibles
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)
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
5HT1A antagonism
antidepressant
anxiolytic
reduces EPS, negative symptoms
5HT2A antagonism
reduces EPS, potentially reduces negative symptoms
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
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
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
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
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
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
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)
Tx mild sedation + psychosis
lorazepam +/- risperidone, olanzepine, or quetiapine
Tx moderate sedation + psychosis
Lorazepam + loxapine / haloperidol
(lorazepam + haloperidol reduces incidence of EPS)
Haloperidol + antihistamine
Olanzepine im
Tx extended period of sedation + psychosis
Zuclopenthixol acetate
not for those who are naive to antipsychotics
Tx insomnia in the context of psychosis
benzodiazepine
zopiclone
trazodone
prn
prn for insomnia should be time-limited
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
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
