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Psychiatric Medication Overdose
Rama B. Rao, MD
Bellevue/New York University Medical
Center
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.
TCA Toxicity
 Anticholinergic/Antihistaminergic
– Somnolence, Tachycardia
  Adrenergic blockade
– Hypotension
 GABA Cl- Channel Antagonist
– Seizures
 Sodium Channel Blockade
– Myocardial Depression, dysrhythmias
Myocardial Cell: Depolarization
Ca2+
Na+
1
0
SR Ca2+
2
3
4
TCA
Ca2+
Na+
TCA
1
pH
0
SR Ca2+
2
3
4
TCA
Ca2+
1
Na+
TCA
pH
0
2
3
4
SR Ca2+
Wide QRS
 > 100 msec predictive of
seizures
1
2
0
 > 160 msec predictive of
dysrythmias
Boehnert M, Lovejoy FH Jr. New Engl J Med 1985;313:474-479
3
4
L
aVR
I
Myocardium
aVR
L
I
With TCA: QRS widening from sodium channel blockade
TCA: Terminal Rightward Axis
L
aVR
I
R in aVR
S in I,L
QRS > 100 msec
TCA Toxicity
aVR
 S in I, L
 R in aVR
 QRS >100 msec
 Drowsy/obtunded
patient
  HR,  BP
Boehnert M, Lovejoy FH Jr. New Engl J Med 1985;313:474-479
Sodium bicarbonate*
1
 Place patient on monitor
 Run strip
0
 Administer bolus of 1 mEq/kg
 Observe for QRS narrowing
 Keep pH 7.5-7.55
 Intubate/hyperventilate if sodium
contraindicated
* Useful for TCA, Cocaine, Type Ia antidysrhythmics
2
3
4
NaHCO3
After NaHCO3
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
St John’s Wort
MECHANISM OF ACTION: TCA, SSRI, MAO-I
Pre-synaptic
DA
Post-synaptic
NE
Neuronal Tissue
Pre-synaptic
DA
Post-synaptic
NE
5HT
Neuronal Tissue
Pre-synaptic
DA
Post-synaptic
Propagation
NE
5HT
Neuronal Tissue
Post-synaptic
Pre-synaptic
DA
Propagation
NE
5HT
MAO
C-O-MT
Pre-synaptic
DA
Post-synaptic
Propagation
NE
5HT
TCA, SSRI
Pre-synaptic
DA
Post-synaptic
Propagation
NE
5HT
MAO-I
Pre-synaptic
DA
Post-synaptic
Propagation
NE
5HT
MAO-I
TCA, SSRI
Serotonin Syndrome
 Excessive serotonergic
tone 5HT1A, 5HT2
 Continuum of
neuropsychiatric
manifestations
Serotonin
Serotonin Syndrome: Major Criteria*
 Confusion
 Chills
 Elevated mood
 Rigidity
 Coma
 Hyperreflexia
 Fever
 Myclonus
 Diaphoresis
 Tremor
4 major, or 3 major and 2 minor
Birmes P CMAJ 2003;168:1439-1442
Minor Criteria: Serotonin Syndrome
 Agitation
 High or low BP
 Nervousness
 Akathisia
 Insomnia
 Incoordination
 Tachypnea
 Mydriasis
 Dyspnea
 Diarrhea
 Tachycardia
4 major, or 3 major and 2 minor
Birmes P CMAJ 2003;168:1439-1442
Fatal Serotonin Syndrome
 Abrupt onset
 Autonomic instability
 Hyperthermia, diaphoresis
 Neuromuscular rigidity, movement disorder
 Altered mental status
 Absence of a neuroleptic or other cause
Serotonin Syndrome
 Most often iatrogenic
 Resolution in 48-96
hours
 Death from uncontrolled
hyperthermia
Serotonin Syndrome:
Therapeutic Goals
 Rapid identification of
Hyperthermia
 Continuous core temperature
monitoring, aggressive cooling,
benzodiazepines for sedation
 Rule out other potential etiologies
Serotonin Syndrome
 Identification of serotonergic
factors, particularly the presence of
monoamine oxidase inhibitors
 ?Role of serotonin antagonists:
cyproheptadine 4 mg po in mild
cases
Drugs Implicated in Serotonin
Syndrome
 MAO-Inhibitors
 MDMA*
 SSRIs
 L-Tryptophan*
 Clomipramine
 Meperidine*
 Venlafaxine
 Dextromethorphan*
 Lithium
 Cocaine*
Pre-synaptic
DA
Post-synaptic
Propagation
NE
5HT
MAO-I
Monoamine Oxidase Inhibitors
 Isolated overdose
– Can be fatal…HTN followed by hypotension and
catecholamine depletion
– Aggressive decontamination
 Tyramine Crisis
– Dietary interaction
– HTN, headache, flushing, vomiting
– Supportive, alpha antagonists, self-limited
What is the finding on this ECG?
Citalopram
 SSRI with toxic
metabolite
 In overdose can
prolong QRS, QTc,
 Seizures
 Delay in onset
Catalano G. Clin Neuropharmacol 2001;24:158-62
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
Atypical Antidepressants
 Venlafaxine
SSRI and NE Uptake inhibition
HTN,HR
 Reboxitine
Selective NE uptake inhibition
HTN
 Bupropion
DA,NE, 5HT re-uptake inhib
SZ, HTN
 Mirtazipine
SSRI, 2 adrenergic blockade
QT, ↓BP, HR
 Trazadone
SSRI, 2 adrenergic blockade
↓BP, HR
Antipsychotics
 CYP2D6 metabolism
 Dystonia
 Akithisia
 NMS
 Overdose:
– QT, hypotension, tachycardia, small pupils
– Depressed mental status
– Anticholinergic
Lithium
 Treated by body like sodium
 Serial levels
 Hyperreflexia, clonus, nystagmus
 Not bound by AC
 Aggressive decontamination with WBI
 Aggressive saline hydration
 Hemodialysis esp for acute on chronic cases
Valproic Acid
 Mood stabilizer
 In toxicity
– Hypoglycemia
– Hyperammonemia
– Depressed mental status
 Supportive therapy
 Carnitine
Summary Poisoning with Psychiatric
Medications:
 Rapid screening for conduction abnormalities
 Rapid evaluation and intervention for
hyperthermic patients
 Aggressive fluid management for agents with 
blockade, or lithium toxicity
 Glucose evaluation