Antidepressants Flashcards
SSRI drug names
Fluoxetine (Prozac)
Sertraline (zoloft)
SNRI drug name
Duloxetine
Tricyclic antidepressant names
Amitriptyline
Desipramine
MAOI drug name
Tranylcypromine
Other Antidepressant Drugs
Buproprion
Mirtazapine
Trazadone
Describe the delayed onset of ADD therapeutic effects
Mood only elevates once the drug level in the system has raised and stabilized (at about 4 days) and stayed high for another 6-8 days. This means you won’t feel better unless you are medication compliant and able to wait 2 full weeks for improvement.
Where is seratonin synthesized?
Mainly in ECL cells - Enterochromaffin-like
What enzyme breaks seratonin down?
Monoamine oxidase - MAO
What is metabolized into melatonin? Where does this happen?
Seratonin (5-HT) - Melatonin is made in the pineal gland.
SSRI mechanism of action
Block the Seratonin Reuptake Transporter (SERT) that brings Seratonin out of the synapse and into the nerve terminal.
They DO NOT affect other amines (like NE)
They DO NOT bind to any receptors.
SSRI in the CNS - acute effects and long-term adaptation
Acutely, more Seratonin in the synapse for longer. Over time, enhanced seratonergic transmission.
SSRI’s initial effects
CNS Stimulation - restlessness, GI upset, usually improves with time.
SSRI’s therapeutic response
Gradual improvement in most depressive symptoms in 1-6 weeks. positive response 70-80%
Non-depression indications for SSRI’s
Anxiety D/O - phobia, panic, PTSD, OCD Eating D/O - bulimia PMDD ADD/ADHD And many more - off-label
SSRI’s ADME
PO Protein bound CYP3A4 - phase 2 glucoronidation Some active metabolites Renal Excretion Long T 1/2 Kinetics are only important for toxic reactions - discontinuation reactions - worse with shorter T1/2 due to faster drop in levels.
SSRI adverse effects
Agitation, insomnia, GI problems, Headache, dizziness, fatigue, weight gain or loss,
Starting with a low dose will help with all of these except the worst one -
sexual dysfunction
SNRI mechanism of action
Block SERT - similar to SSRI’s.
At medium to high doses, they also block the NET - can increase BP at high dose.
Unique indication for SNRI’s
Neuropathic Pain
SSRI’s/SNRI’s overdose toxicity
Generally safe, but when combined with MAOI’s can lead to life threatening Seratonin Syndrome. - Hyperthermia, muscle rigidity, myoclonus, akathisia, hyperreflexia, fluctuating vital signs, and mental status.
What works better? SSRI’s or SNRI’s?
There is no evidence for differences in efficacy, but individuals may respond to one better than the other.
What are some risks associated with Doluxetine?
Shorter t 1/2 - worse discontinuation syndrome
Hypertension at high dose.
Inhibitor of CYP2D6 - DDI’s, can enhance levels of other psychoactive medications.
Trazodone mechanism of action
5-HT2A Receptor blockade (the receptor senses levels of seratonin in the synapse and signals a stop to secretion, so blocking it increases secretion), also a weak SERT blocker and a weak partial agonist at 5-HT1A
Trazodone nontherapeutic mechanisms
Alpha 1 Antagonist - sedation
Active mtabolite mCPP -agonist at several 5HT receptors - unknown effects
Trazodone Clinical Issues
Sedation, orthostatic hypotension, headache, risk of Priapism, CYP3A4 inhibition - DDI’s. Lower overall response than SSRI’s.
Mirtazapine mechanism of action
Alpha 2 antagonist - Enhances NE release, causing increased NE neurotransmission.
Mirtazapine nontherapeutic mechanisms
Potent H1 antagonist - sedation
Weak antagonist at muscarinic and alpha 1 - leading to adrenergic and cholinergic side effects.
Mirtazapine Clinical Issues
Sedation, weight gain, dizziness, anticholinergic action.
May help in some treatment resistant patients.
CYP inhibition
Buproprion Therapeutic mechanism
Blocks DAT (dopamine) and NET. DA effects are unique.
Buproprion nontherapeutic mechanisms
Weak alpha 1 and histamine antagonist, strong antagonist at nicotinic receptor - smoking cessation.
Buproprion Clinical Issues
CNS stimulation, anxiety, insomnia, weight loss, headache, SEIZURES
Few sexual side effects - unique mechanism of action.
Overall lower response rates, may worsen anxiety.
Tricyclics mechanism of action
Block SERT and NET.
Desipramine - prefers NET
Amitriptyline - Prefers SERT
Bock a variety of receptors - Side effects muscarinic, cholinergic, alpha 1 adrenergic, h1 histamine.
TCA’s - Initial effects
Initially - drowsiness, dry mouth, constipation, anxiety, dysphoria, difficulty concentrating.
TCA’s - delayed response
Gradual improvement of most depressive symptoms - positive responses in 80%
TCA ADME
Long T 1/2, some active metabolites, kinetic differences don’t matter, except for the severity of the toxic response when stopping or switching drugs.
What works better, TCA’s, or SSRI’s
No evidence for difference, but individuals may respond better to one than the other.
TCA adverse effects
There are a lot, and noncompliance is common.
NE - tachycardia, palpitations, orthostatic hypotension, delayed orgasm,
Cholinergic - heart block, dry mouth, constipation, urinary retention, blurred vision
Anticholinergic - sedation, confusion, memory impairment, hallucinations
Antihistimine - increased appetite, weight gain.
TCA overdose toxicity
Low TI due to cardiac arrythmias, although desipramine is better than amitriptyline.
Also acidosis, delerium hyperpyrexia, seizures, paralysis, coma.
Treatment for TCA overdose
Supportive, lavage, and lidocaine for arryhthmias.
MAOIs mechanism of action
Irreversibly inhibit Monoamine Oxidase. Increased NE and 5HT in synapse.
MAOI’s - behavioral and clinical effects
Initially - stimulation, agitation, euphoria.
1-6 weeks - stimulation decreases, depression improves.
MAOI Indications
3d line - used for atypical depression.
MAOI interactions
Many drugs are partially detoxified by MAO, so MAOI’s increase levels - lots of DDI’s
Meperidine and Dextromethorphan - Seratonin syndrome, possible fatality
SSRIs, SNRIs, TCA’s, Trazadone - can cause seratonin sydrome when switching to them from MAOI’s - allow at least 2 weeks before starting the new med.
MAOI dietary restriction - what is it and why?
TYRAMINE - in cheese, wine, and other foods. Can cause acute hypertensive crisis.
MAOI adverse effects
CNS stimulation Postural hypotension GI distress Sexual Dysfunction Overdose - uncommon, can cause hyperthermia, shock, coma, seizures.
Use of antidepressants in pregnancy
Tranylcypromine - significant risk. Avoid.
Fluoxetine, sertraline - Category C.
Amitriptyline - possible risk.
What drug can you use for children with major depressive disorder? What is the risk of ADD use in children?
Fluoxetine - Monitor for worsening depression, and suicidal ideation.
Considerations in ADD choice
Tolerance of adverse effects - compliance
Most have similar efficacy, but you don’t know which one is best for your patient until you try.
Poor response to ADD drugs - what do you do?
Check the 5 D's Dose Duration Diagnosis Other Drugs Different treatment - cognitive behavioral, psychotherapy, etc.
