Transcript Neuroleptic Malignat Syndrome (NMS)

Psychotic Disorders
Kheradmand Ali M.D.
Assistant Professor of Shahid
Beheshti Medical University
Mood disorders
“Functional”
disorders
Schizophrenia
“spectrum”
disorders
P
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Y
C
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Substance
induced
Delirium
Dementia
Amnestic d/o
“organic” mental
disorders
Differential Diagnosis
• Medical/surgical/
substance-induced
Psychotic d/o due to GMC
Dementias
Delirium
Medications
Substance induced
Amphetamines
Cocaine
Withdrawal states
Hallucinogens
Alcohol
• Mood disorders
Bipolar disorder
Major depression with psychotic
features
Differential Diagnoses: (Cont)
• Personality disorders
Schizoid
Schizotypal
Paranoid
Borderline
Antisocial
• Miscellaneous
PTSD
Dissociative disorders
Malingering
Culturally specific phenomena:
Religious experiences
Meditative states
Belief in UFO’s, etc
Talking Points
• Schizophrenia is not an excess of dopamine.
• The differentiation between “functional” and
“organic” is artificial.
• Schizophrenia and other psychiatric illnesses are
syndromes.
• Schizophrenia is a diagnosis of exclusion.
Clinical features:
Formal Thought Disorders
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Neologisms
Tangentiality
Derailment
Loosening of associations (word salad)
Private word usage
Perseveration
Non sequiturs
Clinical features:
Delusions
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Paranoid/persecutory
Ideas of reference
External locus of control
Thought broadcasting
Thought insertion,
withdrawal
• Jealousy
• Guilt
• Grandiosity
• Religious delusions
• Somatic delusions
Clinical features:
Hallucinations
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Auditory
Visual
Olfactory
Somatic/tactile
Gustatory
Clinical features:
Behavior
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Bizarre dress, appearance
Catatonia
Poor impulse control
Anger, agitation
Stereotypies , mannerism
Clinical features:
Mood and Affect
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Inappropriate affect
Blunting of affect/mood
Flat affect
Incongruent affect
Dopamine systems
Cell bodies
Projections
Functions
Clinical
implications
Extrapyramidal
symptoms, dystonias,
Tardive dyskinesia
Nigrostriatal
Mesolimbic
Substantia
Nigra
Caudate
and
putamen
Movement
Ventral
tegmental
area, subst.
nigra
Accumbens
amygdala
Olfactory
tubercle
Emotions,
affect,
memory
Positive symptoms
Mesocortical
Ventral
tegmental
area
Prefrontal
Cortex
Thought,
volition,
memory
Blockade here can
worsen negative
symptoms.
Anatomical abnormalities
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Enlargement of lateral ventricles
Smaller than normal total brain volume
Cortical atrophy
Widening of third ventricle
Smaller hippocampus
Physiologic studies:
PET and SPECT
• Generally normal global cerebral flow
• Hypofrontality
• Failure to activate dorsolateral prefrontal
cortex (problem-solving, adaptation, coping
with changes)
Copyright © 2004 Allyn and Bacon
Etiology of Schizophrenia:
Brain Structure and Function
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Congenital Factors
» Damage during gestation or birth
– Obstetrical complications rates high in
patients with schizophrenia
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Reduced supply of oxygen during delivery may
result in loss of cortical matter
» Viral damage to fetal brain
– In Finnish study, schizophrenia rates higher
when mother had flu in second trimester of
pregnancy (Mednick et al., 1988)
– Maternal exposure to parasite associated
with higher rates of schizophrenia in their
offspring
Copyright 2009 John Wiley & Sons, NY
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Etiology of Schizophrenia:
Brain Structure and Function
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Developmental Factors
» Prefrontal cortex matures in adolescence or
early adulthood
» Dopamine activity also peaks in
adolescence
» Stress activates HPA system which triggers
cortisol secretion
– Cortisol increases dopamine activity
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May explain why symptoms appear in
late adolescence but brain damage
occurs early in
life2009 John Wiley & Sons, NY
Copyright
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Etiology of Schizophrenia:
Psychological Stress
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Reaction to stress
» Individuals with schizophrenia and their firstdegree relatives more reactive to stress
– Greater decreases in positive mood and increases
in negative mood
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Socioeconomic status
» Highest rates of schizophrenia among urban
poor.
– Sociogenic hypothesis
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Stress of poverty causes disorder
– Social selection theory
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Downward drift in socioeconomic status
» Research supports social selection
Copyright 2009 John Wiley & Sons, NY
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Etiology of Schizophrenia:
Family Factors
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Schizophrenogenic mother
» Cold, domineering, conflict inducing
» No support for this theory
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Communication deviance (CD)
» Hostility and poor communication
– Family CD predicted onset in one
longitudinal study (Norton, 1982)
– CD not specific to families of
schizophrenic patients
Copyright 2009 John Wiley & Sons, NY
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 Paranoid Type
 Disorganized Type
 Catatonic Type
 Undifferentiated Type
 Residual Type
 Paranoid Type
 Disorganized Type
 Catatonic Type
 Undifferentiated Type
 Residual Type
 Disorganized Speech
 Disorganized Behavior
 Flat or Inappropriate Affect
 Hallucinations and Delusions
– Fragmented or Lacking a Theme
 Often Chronic
 Disorganized Speech
 Disorganized Behavior
Waxy flexibility, rigidity, odd
mannerisms, mimicry
 Flat or Inappropriate Affect
 Hallucinations and Delusions
– Fragmented or Lacking a Theme
 Often Chronic
 Beginnings of Breakdown
 Major Sx of Schizophrenia
 DO NOT Meet Other Criteria
 “Wastebasket” Category
 Have Had One Episode
 Now Mostly Symptom Free
Once a Schizophrenic,
Always a Schizophrenic?
Psychotic Disorders
Onset
Schizophrenia
Usually
insidious
Delusional
disorder
Brief
psychotic
disorder
Symptoms
Many
Course
Duration
Chronic
>6 months
Varies
Delusions
(usually
only
insidious)
Chronic
>1 mo.
Sudden
Limited
<1 mo.
Varies
Workup of New-Onset Psychosis:
“Round up the usual suspects”
• Good clinical history
• Physical exam, ROS
• Labs/Diagnostic tests:
Metabolic panel
CBC with diff
B12, Folate
RPR, VDRL
Serum Alcohol
Urinalysis
Thyroid profile
URINE DRUG SCREEN!!!
CSF/LP
HIV serology
CT or MRI
EEG
Typical Neuroleptics
• Low potency:
– Chlorpromazine
– Thioridazine
– Mesoridazine
• High potency:
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Haloperidol
Fluphenazine
Thiothixene
Loxapine (mid)
Neuroleptic (typicals):
side effects
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Acute dystonia
Parkinsonian side effects (EPS)
Akathisia
Tardive dyskinesia
Sedation, orthostasis, QTC prolongation,
anticholinergic, lower seizure threshold,
increased prolactin
Extrapyramidal Sx. (EPS)
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Acute Dystonias
Antipsychotic-induced Parkinsonism
Akathisia
Tardive Dyskinesia (TD)
• Neuroleptic Malignat Syndrome (NMS)
Acute Dystonias
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Muscle spasm face-neck-trunk-eye-larinx
Early in Tx., young males
Dose Related, Tolerance, incidence 50%
Treatment: Benadryl 50 mg IM (IV 25-50
for laryngospasm), Cogentin 1-4 mg IM
• Prevention reduces incidence to 5%
– Low dose,
– Benztropine 1 mg / every Haldol 5 mg
Antipsychotic-induced
Parkinsonism
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Incidence 50-75% with high pot.
Rigidity
Bradikinesia: mask face-gait problems
Resting Tremor
Flexed Posture
Dif Dx. with flat affect
Tx: Cogentin, Artane 2 mg bid-tid (elder)
– Reduces incidence to 5-10%
Akathisia
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Subjective feeling of restlesness
Unable to sit still, pacing
Incidence 20-30%, lower with low dose
Dif Dx.: psychosis, agitation, anxiety
Tx: Propranolol 30-90 mg/d (not in
asthma or diabetes), Klonopin 1 mg bid
• SSRI Antidepressants cause akathisia too
Tardive Dyskinesia (TD)
• Slow choreo-athetotic movements
• Oro-facial muscles
• Risk 4% per year of exposure
– Risk factors elderly women, mood DO, diab.
• Risk management
– document informed consent, AIMS Tests
• Tx?: Vit E 1600 U/d, Clozapine low risk
Neuroleptic Malignant
Syndrome (NMS)
• Medical Emerg, mort. 20% (now 4%)
• 1. Fever >100.4F / 37.5C
• 2. Severe EPS: lead-pipe/cogwheel
rigidity, sialorrhea, oculogyric crisis
• 3. Autonomic DysFx: BP fluctuations,
tachycardia, tachypnea, diaphoresis
• Also: Alt. conciousness, delirium,
leukocytosis (>15.000 WBC), CPK > 300,
seizures, arrithmias, mioglobinuria, ARF
NMS
• Incidence 0.1-1%, (60% of it in 1st 2 wks)
• Risk factors: multiple IM injections, high
dose, rapid increase of dose agitation,
dehydration, heat, lithium use
• Tx: STOP ALL antipsychotics, also
antiemetic Reglan (Metoclopramide),
antidepr. Amoxapine
NMS Treatment
• Stop ALL Antipsychotics
• Dif. Dx: fever & delirium
• Dantrolene (muscle relax) 1-3 mg/kg/day
NTE 10 mg/kg/d
• Bromocriptine (DA Agonist) 5 mg tid-qid
• Supportive Tx:
– IV fluids, antipyretics, cooling blankets,
close cardiac & renal monitoring
Atypical Antipsychotics:
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Risperidone
Olanzapine
Quetiapine
Clozapine
Ziprasidone
Aripiprazole (new-partial DA agonist)
Serotonergic Pathways and Innervation
Hypo = hypothalamus
SN = substantia nigra
Thal = thalamus
Atypical antipsychotics
MARTA (multi acting receptor targeted agents)
• clozapine, olanzapine, quetiapine
SDA (serotonin-dopamine antagonists)
• risperidone, ziprasidone, sertindole
Selective D2/D3 antagonists
• sulpiride, amisulpiride
Atypical Antipsychotics: Side Effects
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Sedation
Hyperglycemia, new-onset diabetes
Anticholinergic effects
Less prolactin elevation
QTC prolongation
Some EPS
Increased lipids
ESTIMATED MEAN WEIGHT GAIN AT 10 WEEKS
Mean change in body weight (kg)
A comprehensive literature search identified 78 studies that included data on weight change in •
patients treated with a specific antipsychotic.
5 For each agent a meta-analysis and random effects regression estimated the change in weight •
at 10 weeks of treatment.
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2
1
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Allison DB, Mentore JL, Heo
M, et al: Weight gain associated with conventional
and newer antipsychotics: a meta- Analysis. AJP, 1999.
Atypical Antipsychotics In Vivo Binding Affinities
Haloperidol
Clozapine
Quetiapine
Ziprasidone
5HT2A
D2
D1
Risperidone
Alpha 1
Musc
Olanzapine
H1
5HT1A (agonist)
Casey 1994
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