17 - Antidepressants Flashcards
What are MAOIs? How long is their wash-out period?
- Irreversible inhibitors of MAO A and B
- 2 weeks before new enzyme is synthesized
How many phases of MAOI overdose?
4
Phase 1 of MAOI overdose
- Asymptomatic (latent) period
- Up to 6-12 h
- Monitor for 24h post-ingestion
Phase 2 of MAOI overdose
- Neuromuscular excitation and sympathetic hyperactivity
- Hypertension, hyperreflexia, hyperthermia
- Tremor, myoclonus, seizures, agitation, rigidity
Phase 3 of MAOI overdose
- CNS depression and possible CV collapse
- Hypotension
Phase 4 of MAOI overdose
Secondary complications for survivors
MAOI overdose tx
- Severe hypertension -> tx w/ short-acting antihypertensive
- Arrhythmias -> standard anti-arrhythmic
- Hypotension -> direct acting vasopressors (not indirect); start low
- Charcoal
- Hyperthermia -> treat aggressively
- Rigidity -> BZDs, dantrolene (muscle relaxant) to prevent rhabdomyolysis
Foods to avoid w/ MAOIs
- Cheese (all aged)
- Alcoholic beverages -> red wine, sherry, cognac, beer
- Fish -> smoked, caviar
- Meat -> fermented, salami, some sausage
Describe the MAOI-cheese reaction
- Hypertensive crisis from indirect acting amines
- Direct acting don’t require MAO for their metabolism
- Catabolized by COMT
- Tyramine = indirect acting amine
- Peripheral effects as it doesn’t cross BBB
- Causes NE release from peripheral noradrenergic neurons
- Normally, little absorbed
- Dietary amine metabolized by GI MAO-A
What do TCAs block in the brain?
- Block serotonin and NE reuptake
- Block histamine, muscarinic, and alpha-adrenergic receptors
Cardiac effects of TCAs at usual doses
- Hypertension, tachycardia
- Slowed cardiac conduction
- Antiarrhythmic properties
- Orthostatic hypotension
Px at high risk for TCA cardiac adverse events
- Elderly
- CV disease
- Drug interactions (increased levels)
- Overdose cases
Central anticholinergic effects of TCAs
- Agitation
- Hallucinations
- Confusion
- Sedation
- Coma, seizures
Peripheral anticholinergic effects of TCAs
- Hypertension, tachycardia, hyperthermia
- Mydriasis
- Dry, flushed skin
- Decreased GI motility
- Urinary retention
CV effects of TCAs at toxic doses
- Intraventricular conduction delay (QRS prolongation)
- Sinus tachycardia
- Ventricular arrhythmias
- Hypotension
CNS effects of TCAs at toxic doses
- Coma
- Delirium
- Myoclonus
- Seizures
Other effects of TCAs at toxic doses
- Hyperthermia
- Ileus
- Urinary retention
Risk factors that increase risk of TCA toxicity
- Pre-existing heart condition
- Electrolyte abnormalities
- Hepatic insufficiency
- Stimulant drug use
- Multiple drugs that increase QT interval
- Increased dose
TCA overdose – general management
- *Treat symptomatically
- Airway if needed, IV-line, cardiac monitoring, EKG
- Decreased LOC => O2, dextrose, naloxone, thiamine, ABGs
- Stomach lavage
- Charcoal 50-100 g + cathartic
- Usually 10-20 mg/kg is considered life-threatening (limit Rx to 1 g if suicidal)
- Sx from as little as 3-4 times daily dose
What is the most common cause of death in TCA overdose?
Refractory hypotension (due to vasodilation or impaired cardiac contractility)
Tx of TCA induced orthostatic hypotension
- Intravascular volume expansion
- Sodium bicarbonate, vasopressors (NE) or inotropes (dopamine)
- Correct hyperthermia, acidosis, seizures
Tx of TCA induced CNS toxicity
- Confusion, agitation, hallucinations -> supportive therapy and BZDs
- Coma, myoclonus -> coma usually resolves in 24 h
- Seizures -> usually brief but often occur immediately before cardiac arrest
- Acidemia from seizures may predispose to arrhythmias
- Usually responsive to IV BZDs (midazolam infusion)
- Refractory -> barbiturates or propofol
- Phenytoin no longer recommended (b/c proarrhythmic w/ limited efficacy)
What is the most common mechanism of TCA associated death?
Myocardial depression, ventricular tachycardia, or ventricular fibrillation
What is a predictor of arrhythmias?
QRS duration > 0.10 s
____ can reduce arrhythmias and hypotension caused by TCAs
Sodium bicarbonate
Can anti-arrhythmics be given to TCA-induced arrhythmias?
No, b/c pro-arrhythmic
What can be used to treat TCA cardiotoxicity?
Lipid emulsion b/c TCAs are highly lipophilic
TCA overdose – length of tx
- Anti-cholinergic effects after a large ingestion may result in slow absorption
- Asymptomatic w/ normal ECG x 6 h w/ only tx GI decontamination -> not likely to develop toxic effects
- If symptomatic w/ altered mental status, seizures, or cardiac dysrhythmias -> monitor in ICU x 12-24 h after all sx resolved and all supportive interventions are d/c
- If parameters remain normal then psychiatry to evaluate
Venlafaxine safety
- In general, safety profile good
- Recent data indicated that may not be as safe as SSRIs; closer to TCAs
- Rare reports of conduction disturbances
- Potentially may increase QRS; pro-arrhythmic in overdose or poor metabolizers
- Blood pressure increases
- Dose dependent response
- Usually reversible upon d/c
- Risk greater w/ increased age
Symptoms of venlafaxine overdose?
- Overdoses reported –> seizures, hypotension, sinus tachycardia
- Serotonin syndrome
- Drug interactions w/ serotonergic agents (MAOIs, SSRIs)
When is venlafaxine contraindicated?
- Relatively contraindicated in px w/ high risk of overdoses and/ or pre-existing seizures and cardiac disease
- Watch in subjects who are poor CYP2D6 metabolizers, or concomitant drugs that inhibit CYP2D6
Desvenlafaxine safety
- Minor effects w/ mild hypertension and tachycardia
- Risk of seizures or serotonin toxicity is low
Signs and symptoms of duloxetine overdose
- Somnolence
- Serotonin syndrome
- Seizures
- Vomiting
SSRIs toxic effects and tx
- Tremor, sinus tachycardia, N/V/D, seizures, serotonin syndrome
- Mild bradycardia may occur in OD
- Lower incidence of mortality vs. TCAs
- Tx = charcoal + supportive care
Causes of serotonin syndrome
- Drugs that inhibit breakdown of 5-HT -> MAOIs
- Drugs that block re-uptake of 5-HT -> SSRIs, venlafaxine, trazodone, clomipramine, dextromethorphan, meperidine, pentazocine, cocaine
- Drugs that are 5-HT precursors or agonists -> lithium, buspirone, L-tryptophan, LSD, psilocybin
- Drugs that enhance 5-HT release -> MDMA
Tx of serotonin syndrome
- Supportive care
- Neuromuscular sx -> BZDs
- Increased temp -> Tylenol, cooling blankets
- Severe rigidity -> dantrolene
- Severe sx -> cyproheptadine 4 mg PO q4h; 5-HT antagonism; watch anticholinergic and antihistaminic properties
Cognitive sx of serotonin syndrome
- Agitation
- Mental status changes (confusion, hypomania)
Autonomic dysfunction sx of serotonin syndrome
- Diaphoresis
- Diarrhea
- Fever
- Shivering
Neuromuscular sx of serotonin syndrome
- Incoordination
- Myoclonus
- Tremor
- Hyperreflexia
Citalopram and cardiac toxicity
- Dose related QT prolongation
- High risk in metabolic disturbance and pre-existing cardiac disease
- Potential increased risk of Torsades de Pointes
- Maximum dose = 40 mg/day
- 20 mg in elderly or hepatic impairment
Bupropion safety
- May cause sinus tachycardia but not usually associated w/ conduction abnormalities
- Study in depressed cardiac px -> no significant effect on heart (conduction, arrhythmias, hypotension, pulse)
- XL product = delayed onset seizures
- Must monitor for longer time
Mirtazapine safety
- Increased 5-HT and NE + serotonin blocker
- Mild-moderate anticholinergic
- Antihistamine effects
- *Watch for serotonergic and anticholinergic effects in overdose
- Case series -> no cardiac effects, no QTc prolongation
