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Newer Antidepressants and Serotonin Syndrome. Presented by Dr. Bloxdorf Prepared by A. Hillier. General Principles. Newer antidepressants termed atypical, heterocyclic or second generation

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newer antidepressants and serotonin syndrome

Newer Antidepressants and Serotonin Syndrome

Presented by Dr. Bloxdorf

Prepared by A. Hillier

general principles
General Principles
  • Newer antidepressants termed atypical, heterocyclic or second generation
  • Prescribed for depression, anxiety disorder, panic disorder, personality disorders, OCD and eating disorders
  • Differentiated from TCA’s and MAOI’s

▪ More selective ▪ Less toxicity

▪ Fewer fatalities

  • More likely to produce Serotonin Syndrome
general principles3
General Principles
  • No cardiotoxicity or conduction delays that are seen with TCA’s
  • No associated tyramine reactions like MAOI’s
  • Negligible affinity for acetylcholine, dopamine, GABA-A, glutamate or β-adrenergic receptors
  • Higher safety margin than MAOI’s and TCA’s
general principles4
General Principles
  • Poorly cleared by hemodialysis, hemofiltration, forced diuresis, whole bowel irrigation or activated charcoal
  • Not detected by routine plasma/urine testing
  • Primarily CYP-450 hepatic metabolization
  • If taken with MAOI’s may precipitate serotonin syndrome
trazodone overview
Trazodone-Overview
  • Indicated for depression and insomnia
  • Low fatality rate (1 in 1200 exposures)
  • Unrelated to other antidepressants
  • Half-life up to 13 hours with overdose
  • Common side effects

▪ Priapism ▪ Drowsiness ▪ Dry mouth

▪ Nausea ▪ Orthostatic hypotension

trazodone acute overdose
Trazodone-Acute Overdose
  • No established toxic dose-no serious toxicity up to 2 grams
  • Most common is CNS depression
  • Severe Ingestion

▪ Ataxia ▪ Dizziness ▪ Seizures

▪ Coma ▪ Hypotension

  • Treatment

▪ Supportive ▪ Charcoal

▪ Lavage for massive ingestion

bupropion overview
Bupropion-Overview
  • Indicated for depression and nicotine cessation
  • Half-life up to 20 hours
  • Common side effects

▪ Dry mouth ▪ Dizziness ▪ Confusion

▪ Agitation ▪ Nausea ▪ Blurred vision

▪ Headache ▪ Constipation ▪ Tremor

  • Rare side effects

▪ Rash ▪ Stevens-Johnson ▪ Seizure

bupropion acute overdose
Bupropion-Acute Overdose
  • Low-toxic-to therapeutic ratio
  • Most common-sinus tachycardia
  • Severe Ingestion

▪ Lethargy ▪ Generalized seizure

▪ Coma ▪ Cardiac arrest

  • Treatment

▪ Gastric Lavage ▪ Activated charcoal

▪ Benzodiazepines ▪ Phenobarbital

nefazodone acute overdose
Nefazodone-Acute Overdose
  • Relatively safe in overdose
  • No fatalities with overdose up to 11 grams
  • Most common symptoms

▪ Nausea ▪ Vomiting ▪ Somnolence

  • Supportive Treatment

Mirtazapine-Acute Overdose

  • Limited toxicity in overdose
  • Most common symptoms

▪ Sedation ▪ Confusion

▪ Sinus tachycardia ▪ Mild hypertension

  • Supportive Treatment
selective serotonin receptor inhibitors
Selective Serotonin Receptor Inhibitors
  • Inhibit presynaptic serotonin reuptake
  • Most commonly prescribed class of antidepressants
  • Fatalities uncommon (1 in 1000)
  • Long half life (15 hours up to 14 days)
selective serotonin receptor inhibitors11
Selective Serotonin Receptor Inhibitors
  • Adverse events

▪ Nausea ▪ Anorexia

▪ Serotonin syndrome ▪ Headache

▪ Sedation ▪ Insomnia

▪ Dizziness ▪ Fatigue

▪ Tremor ▪ Nervousness

▪ Seizures ▪ Extrapyramidal symptoms

▪ SIADH

selective serotonin receptor inhibitors12
Selective Serotonin Receptor Inhibitors
  • Acute Overdose
    • High therapeutic-to-toxic ratio
    • Fatalities uncommon
    • 50% of overdoses remain asymptomatic
    • Most symptoms similar to adverse event profile
    • Less frequent

▪ Agitation ▪ Hallucinations ▪ Seizures

▪ Hypertension ▪ Hypotension ▪ Widened QRS

▪ Prolonged QTc

selective serotonin receptor inhibitors13
Selective Serotonin Receptor Inhibitors
  • Treatment
    • IV
    • Cardiac monitor
    • Activated charcoal 1 gm/kg
    • Gastric lavage probably unnecessary
    • Syrup of Ipecac-contraindicated
    • Prolonged QRS/QTc-Sodium bicarbonate
    • Seizures-Benzodiazepines
    • Serotonin syndrome-Cyproheptadine
venlafaxine acute overdose
Venlafaxine-Acute Overdose
  • Half-life of 11 hours
  • Most common effects

▪ Tachycardia ▪ Hypertension

▪ Diaphoresis ▪ Tremor

▪ Mydriasis ▪ Sedation

  • More severe effects

▪ Coma ▪ Generalized seizures

▪ Widened QRS ▪ Prolonged QTc

venlafaxine acute overdose15
Venlafaxine-Acute Overdose
  • Treatment
    • IV
    • Monitor
    • Gastric lavage
    • Activated charcoal
    • Seizures-Benzodiazepines
    • QRS widening-Sodium bicarbonate
    • Hypertension-Nitroprusside/Esmolol or Phentolamine
        • Avoid β-blockers
serotonin syndrome
Serotonin Syndrome
  • Rare idiosyncratic drug-induced reaction
  • Most cases occur at therapeutic levels
  • Less than 13% occur with overdose
  • Characterized by alterations in
    • Cognition and behavior
    • Autonomic nervous system
    • Neuromuscular activity
  • Mortality rate of 11%
serotonin syndrome17
Serotonin Syndrome
  • SS most often occurs after routine medication increase or addition of another 5-HT stimulating agent
  • True incidence of SS is unknown
  • SS is often difficult to diagnose because of varying symptoms

▪ Mild cases attributed to psychiatric disorders

▪ More severe cases attributed to NMS

  • EP’s may inadvertently precipitate SS by prescribing tramadol, dextromethorphan or meperidine
serotonin syndrome19
Serotonin Syndrome
  • Muscle rigidity
    • Most often found in the lower extremities-may be valuable clinical marker
  • Ataxia
    • Check for lower extremity hypertonia
  • Hyperthermia
    • Usually mild-moderate, but reports up to 41oC
  • Seizures
    • Always generalized and usually short lived
serotonin syndrome20
Serotonin Syndrome
  • Unilateral muscle rigidity or focal neurologic findings have not been reported
  • Hypertension reported twice as often as hypotension
  • SS is a clinical diagnosis
  • Lab testing done to rule-out other causes of symptoms
serotonin syndrome21
Serotonin Syndrome
  • Treatment
    • No accepted guidelines for SS treatment
    • Stop offending drugs
    • Benzodiazepines for patient comfort and rigidity
    • Monitor closely for rhabdomyolysis and metabolic acidosis
    • Approximately 25% will require intubation
    • Usually dramatic improvement within 24 hours
serotonin syndrome medications
Serotonin Syndrome Medications
  • Cyproheptadine
    • Initial dose: 4-8 mg PO
    • May repeat in 2 hours if no response
    • Discontinue is no response noted after 16 mg
  • Dantrolene
    • 0.5-2.5 mg/kg IV every 6 hours
    • Maximum 10 mg/kg in 24 hours
summary
Summary
  • SSRI overdose pales in comparison to MAOI’s and TCA’s
  • Still can have significant morbidity and mortality
  • Most of the management is supportive after decontamination
  • Beware of tramadol, dextromethorphan and meperidine in anyone taking SSRI’s, TCA’s or MAOI’s
questions
Questions
  • All of the following may precipitate serotonin syndrome except:
    • Paroxetine
    • Meperidine
    • Fentanyl
    • Tramadol
    • Dextromethorphan
questions25
Questions
  • Serotonin syndrome may present like all of the following except:
    • Sympathomimetic syndrome
    • Neuroleptic malignant syndrome
    • Acute psychosis
    • Rhabdomyolysis
    • Acute unilateral stroke
questions26
Questions
  • Basic management for any acute overdose consist of:
    • Rectal exam
    • Call poison control
    • HgbA1C
    • VDRL/RPR
    • Punitive Gastric Lavage
questions27
Questions
  • All of the following are included in the serotonin syndrome triad except:
    • Hepatic dysfunction
    • Cognitive dysfunction
    • Autonomic dysfunction
    • Neuromuscular dysfunction
questions28
Questions
  • With the newer class of antidepressants which of the following are true:
    • There are not detected by routine lab tests
    • Treatment is mostly supportive
    • They are poorly cleared by hemodialysis, forced diuresis or activated charcoal
    • Have no significant interactions with MAOI’s
    • All of the above are true
answers
Answers
  • C-Fentanyl has never been reported to precipitate SS, however all the others can
  • E-SS may present like all the other responses, but acute focal CVA should make you think of another diagnosis
  • B-Even with the most mundane ingestion, you should make the call to Poison Control
  • A-Although due to rhabdomyolysis etc. you may see liver dysfunction, it is not part of the presenting triad
  • E-All of the above are true