TCA and Serotonin ReUptake Inhibitors

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TCA and Serotonin Re-Uptake Inhibitors

• Rama B. Rao, MD
• Bellevue/New York University Medical Center

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Tricyclic Antidepressants

• A patient takes 30 tablets of nortriptylline in a
  suicide attempt, she calls her family member who
  summons an ambulance.
• On arrival, the paramedics note she is
  unresponsive, tachycardic, and hypotensive.
• She seizes.

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TCA Toxicity

• Anticholinergic/Antihistaminergic
• Somnolence, Tachycardia
• ? Adrenergic blockade
• Hypotension
• GABA Cl- Channel Antagonist
• Seizures
• Sodium Channel Blockade
• Myocardial Depression, dysrhythmias

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Myocardial Cell Depolarization
Ca2
Na
1
2
0
3
SR
4
Ca2
6
TCA
Ca2
Na
TCA
1
2
pH
0
3
SR
4
Ca2
7
TCA
1
Ca2
Na
2
TCA
0
3
pH
4
SR
Ca2
8
Wide QRS
1
2

• gt 100 msec predictive of seizures
• gt 160 msec predictive of dysrythmias

3
0
4
Boehnert M, Lovejoy FH Jr. New Engl J Med
1985313474-479
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L
aVR
I
Myocardium
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L
aVR
I
With TCA QRS widening from sodium channel
blockade
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TCA Terminal Rightward Axis
L
aVR
I
R in aVR
S in I,L
QRS gt 100 msec
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TCA Toxicity

• S in I, L
• R in aVR
• QRS gt100 msec
• Drowsy/obtunded patient
• ? HR, ? BP

aVR
Boehnert M, Lovejoy FH Jr. New Engl J Med
1985313474-479
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Sodium bicarbonate
1
2

• Place patient on monitor
• Run strip
• Administer bolus of 1 mEq/kg
• Observe for QRS narrowing
• Keep pH 7.5-7.55
• Intubate/hyperventilate if sodium contraindicated

0
3
4
NaHCO3
Useful for TCA, Cocaine, Type Ia
antidysrhythmics
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After NaHCO3
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TCA Toxicity General Management

• 2 Large bore intravenous lines
• Continuous ECG monitoring
• Assessment for QRS widening, terminal RAD, and
  response to sodium bicarbonate
• Aggressive decontamination
• Benzodiazepines for seizure management

Fingerstick blood glucose
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St Johns Wort
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MECHANISM OF ACTION TCA, SSRI, MAO-I
Pre-synaptic
Post-synaptic
DA
NE
Neuronal Tissue
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Pre-synaptic
Post-synaptic
DA
NE
5HT
Neuronal Tissue
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Pre-synaptic
Post-synaptic
Propagation
DA
NE
5HT
Neuronal Tissue
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Post-synaptic
Pre-synaptic
Propagation
DA
NE
5HT
MAO
C-O-MT
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Pre-synaptic
Post-synaptic
Propagation
DA
NE
5HT
TCA, SSRI
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Pre-synaptic
Post-synaptic
Propagation
DA
NE
5HT
MAO-I
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Pre-synaptic
Post-synaptic
Propagation
DA
NE
5HT
MAO-I
TCA, SSRI
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Serotonin Syndrome

• Excessive serotonergic tone 5HT1A, 5HT2
• Continuum of neuropsychiatric manifestations

Serotonin
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Serotonin Syndrome Major Criteria

• Confusion
• Elevated mood
• Coma
• Fever
• Diaphoresis

• Chills
• Rigidity
• Hyperreflexia
• Myclonus
• Tremor

4 major, or 3 major and 2 minor Birmes P CMAJ
20031681439-1442
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Minor Criteria Serotonin Syndrome

• Agitation
• Nervousness
• Insomnia
• Tachypnea
• Dyspnea
• Tachycardia

• High or low BP
• Akathisia
• Incoordination
• Mydriasis
• Diarrhea

4 major, or 3 major and 2 minor Birmes P CMAJ
20031681439-1442
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Fatal Serotonin Syndrome

• Abrupt onset
• Autonomic instability
• Hyperthermia, diaphoresis
• Neuromuscular rigidity, movement disorder
• Altered mental status
• Absence of a neuroleptic or other cause

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Serotonin Syndrome

• Most often iatrogenic
• Resolution in 48-96 hours
• Death from uncontrolled hyperthermia

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Serotonin Syndrome Therapeutic Goals

• Rapid identification of Hyperthermia
• Continuous core temperature monitoring,
  aggressive cooling, benzodiazepines for sedation
• Rule out other potential etiologies

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Serotonin Syndrome

• Identification of serotonergic factors,
  particularly the presence of monoamine oxidase
  inhibitors
• ?Role of serotonin antagonists

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Drugs Implicated in Serotonin Syndrome

• MAO-Inhibitors
• SSRIs
• Clomipramine
• Venlafaxine
• Lithium

• MDMA
• L-Tryptophan
• Meperidine
• Dextromethorphan
• Cocaine

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Citalopram

• SSRI with toxic metabolite
• In overdose can prolong QRS, QTc,
• Seizures
• Delay in onset

Catalano G. Clin Neuropharmacol 200124158-62
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Citalopram Overdose

• Immediate cardiac monitoring for QTc, IV lines
• Assess and correct electrolytes, especially K,
  Ca2, Mg2
• Decontamination
• Use of Mg2 for torsade
• Admission of minimum 24 hours of cardiac
  monitoring

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Myocardial Cell
Ca2
2
3
1
AC
cAMP
SR
Ca2
4
?
G
ATP
5