Drugs - Antidepressant Toxicity and Side Effects

Question 1

What are the toxicity and side effects of TCAs?

Answer 1

• Mania
• Toxic psychosis due to anticholinergic effects of tertiary TCAs
• REM rebound
• abrupt withdrawal symptoms
• EPS - amoxapine (not a TCA)
• agitation - protriptyline
• seizures - worst TCA is clomipramine
• orthostasis - block alpha-1
• sedation, weight gain due to block of H1 receptor
• sexual dysfunction
• cardiovascular toxicities -> quinidine -like effects in overdose -> may lead to VF
• interact with MAOIs causes increase in norepinephrine which may lead to hypertensive crisis (relative contraindication)

Question 2

What are the toxicity and side effects of SSRIs and SNRIs?

Answer 2

• Minimal anticholinergic and antihistamine activity so minimal orthostasis
• nausea, vomiting, diarrhea
• headache
• insomnia because some are activating
• agitation, akathisia, anxiety, nervousness - fluoxetine
• inhibition of CYP 450 enzymes (least with sertraline and citalopram)
• seizures - lower incidence than TCAs
• sexual dysfunctions
• interact with MAOIs - serotonin syndrome
• increased diastolic blood pressure in venlafaxine and duloxetine at higher doses

Question 3

What are the toxicity and side effects of MAOIs?

Answer 3

• Insomnia, irritability, agitation - tranylcypromine amphetamine derivative
• REM rebound when discontinue
• orthostatic hypotension is the most common side effect
• hepatic toxicities - hydrazines
• hypertensive crisis - cheese affect in foods containing tyrosine or tyramine, OTC decongestants, L-DOPA
• serotonin syndrome with SSRIs, triptans
• severe encephalopathy with Demerol
• anticholinergic effects even though they don’t block muscarinic receptors is believed to be an indirect reduction of net cholinergic tone due to increased sympathetic tone