DSA11 - Antidepressants

Fluoxetine MoA

SSRI, longest half life (low risk of discontinuation syndrome)

Fluoxetine Tx

FIRST CHOICE FOR Depression

Fluoxetine S/E

TRANSIET WT LOSS (NAUSEA-INDUCED), Sexual Dysfunction, GI Disturb, INITIAL AGITATION/INSOMINA, Sedation, Hyponatremia (SIADH) + Potent Inhibitor of CYP2D6

Sertraline MoA

SSRI

Sertraline Tx

FIRST CHOICE FOR Depression

Sertraline S/E

HIGHEST GI S/Es (Upset Stomach & Diarrhea --> tolerance later) + Sexual Dysfunction, Initial Agitation/Insomnia, Sedation, Hyponatremia (SIADH)

Paroxetine MoA

SSRI, shortest half life

Paroxetine Tx

FIRST CHOICE FOR Depression

Paroxetine S/E

NOT DURING PREGNANCY; HIGH RISK Of SSRI DISCONTINUATION SYNDROME + More Wt Gain, SEXUAL DYSFUNCTION!, Potent CYP2D6 Inhibitor

Citalopram MoA

SSRI (Racemic drug mixture), Low DDI

Citalopram Tx

FIRST CHOICE FOR Depression (NOT for OCD)

Citalopram S/E

Sexual Dysfunction, GI Disturb, Initial Agitation/Insomnia, Sedation, Hyponatremia (SIADH), QTc Prolongation

Escitalopram MoA

SSRI (S-enantiomer of Citalopram --> ACTIVE); MOST SEROTONIN SELECTIVE of SSRIs

Escitalopram Tx

Depression (NOT for OCD); Low potential for DDIs (limited CYP450 interactions)

Escitalopram S/E

Sexual Dysfunction, GI Disturb, Initial Agitation/Insomnia, Sedation, Hyponatremia (SIADH)

Fluvoxamine MoA

SSRI

Fluvoxamine Tx

OCD ONLY!

Fluvoxamine S/E

Sexual Dysfunction, GI Disturb, Initial Agitation/Insomnia, Sedation, Hyponatremia (SIADH)

How long do TCAs, 2nd Gens, SSRIs, MAO-Is take to be effective?

1-3 wks for clinical effect, 3-6 wks for max dose effect (If trial of max dose doesn't work after 4-6 wks --> UNSUCCESSFUL)

How might Hyponatremia present?

-RAPID = SEIZUERS

-SLOW = Weakness, Confusion

SSRIs may increase suicidal (thought/attempt), but NOT increase suicidal (thought/attempt)

thought; attempt

Venlafaxine/Desvenlafaxine MoA

2nd Gen Antidepressant - SNRI (blocks reuptake of both serotonin and NE --> more serotonin available in synaptic cleft)

Venlafaxine/Desvenlafaxine Tx

Depression

Venlafaxine/Desvenlafaxine S/E

RISK OF HTN & TACHYCARDIA! (peripheral NE effects), MORE TOXICITY in overdose than SSRIs, More intense SSRI Discontinuation Syndrome

Duloxetine MoA

2nd Gen Antidepressant - SNRI (blocks reuptake of both serotonin and NE --> more serotonin available in synaptic cleft); NO Dopamine Effect

Duloxetine Tx

Depression, Peripheral Pain of Depression/Diabetic Neuropathy/OA/MSK (Mgmt)

Duloxetine S/E

Low Sexual S/Es

Atomoxetine MoA

SNRI (blocks reuptake of both serotonin and NE --> more serotonin available in synaptic cleft)

Atomoxetine Tx

Depression (FAST Onset), ADHD, Cognitive Disengagement Syndrome (CDS)

Bupropion MoA

2nd Gen Antidepressant - Blocks NE & Dopa reuptake

Bupropion Tx

Depression, Nicotine Addiction (Smoking Cessation via inhibition of neuronal Nicotinic receptors) + LOW SEXUAL ISSUES

Bupropion S/E

Seizure risk at high doses (C/I in seizure disorder), C/I w/ Eating Disorders, Increased anxiety

What is a benefit of treating with Bupropion instead of other Antidepressants?

Unlike other antidepressants, treating Depression from Bipolar Disorder accidentally WON'T induce a manic state (doesn't involve serotonergic mechanisms)

Mirtazapine MoA

2nd Gen Antidepressant - Alpha 2 adrenergic presynaptic antagonist + 5-HT2 & 5-HT3 Antagonist --> Increase in 5-HT firing from more NE release & Alpha-2 block on 5-HT terminals

Mirtazapine Tx

Depression

Mirtazapine S/E

MORE WT GAIN + Less sexual & GI S/Es, Risk of Agranulocytosis

Trazodone MoA

2nd Gen Antidepressant; 5-HT2 antagonist + Weak, Selective 5-HT reuptake inhibitor

Trazodone Tx

Depression, Sleep Issues (used w/ MAOIs to ofset insmonia from MAOIs), Anxiety Issues; Less lethal than TCA overdose + Few antimusc effects

Trazodone S/Es

Priapism, HIGHLY SEDATIVE

Amitriptyline MoA

Tertiary TCA (non-selective); Serotonin & NE reuptake blocker

Amytriptyline Tx

Depression, Chronic Pain --> No Response to SSRIs = Panic Disorder, OCD, Anxiety

Amitriptyline S/E

Anticholinergic (dry mouth, constipation, urinary retention, blurred vision, confusion); Metabolic/Endocrine (Wt Gain, Sexual Disturbances); Antiadrenergic (OH, fainting, arrhythmias); Antihistaminergic (sedation); HIGH CNS Sedation (tremor, insomina)

Why is Amitriptyline overdose so dangerous?

- Causes LETHAL Cardiac Dysrhythmias

- Dialysis is ineffective at removal (large Vd + High plasma protein binding)

Doxepin MoA

Tertiary TCA (non-selective)

Doxepin Tx

Depression, Sleep Aid, Chronic Pain --> No Response to SSRIs = Panic Disorder, OCD, Anxiety

Doxepin S/E

Anticholinergic (dry mouth, constipation, urinary retention, blurred vision, confusion); Metabolic/Endocrine (Wt Gain, Sexual Disturbances); Antiadrenergic (OH, fainting, arrhythmias); Antihistaminergic (sedation); HIGH CNS Sedation (tremor, insomina)

Nortriptyline MoA

Secondary TCA (more selective) + MORE HISTAMINERGIC

Nortriptyline Tx

Depression (RECOMMENDED) --> No Response to SSRIs = Panic Disorder, OCD, Anxiety

Nortriptyline S/E

Anticholinergic (dry mouth, constipation, urinary retention, blurred vision, confusion); Metabolic/Endocrine (Wt Gain, Sexual Disturbances); Antiadrenergic (OH, fainting, arrhythmias); Antihistaminergic (sedation); CNS Sedation (tremor, insomina)

Desipramine MoA

Secondary TCA (more selective) + MOST NONADRENERGIC

Desipramine Tx

Depression (RECOMMENDED) --> No Response to SSRIs = Panic Disorder, OCD, Anxiety

Desipramine S/E

Anticholinergic (dry mouth, constipation, urinary retention, blurred vision, confusion); Metabolic/Endocrine (Wt Gain, Sexual Disturbances); Antiadrenergic (OH, fainting, arrhythmias); Antihistaminergic (sedation); CNS Sedation (tremor, insomina)

Why are TCAs less preferred compared to SSRIs for Depression Tx (and used for specific indications)?

They're more potentially lethal

Phenelzine MoA

MAO-Is (nonselective, IRREVERSIBLE inhibitor) --> Increased NE, 5-HT, DA in pre-synaptic terminal

Phenelzine Tx

Tx Resistant Depression (3rd/4th Tx)

Phenelzine S/E

Hypertensive crisis IF NO washout before TCAs, SSRIs, SNRIs added + STRICT DIET (NO TYRAMINE FOODS - aged meats/cheese, beer), High toxicity in overdose

Tranylcypromine MoA

MAO-Is (nonselective, REVERSIBLE inhibitor, but LONG ACTING)--> Increased NE, 5-HT, DA in pre-synaptic terminal

Tranylcypromine Tx

Tx Resistant Depression (3rd/4th Tx)

Tranylcypromine S/E

Hypertensive crisis IF NO washout before TCAs, SSRIs, SNRIs added + STRICT DIET (NO TYRAMINE FOODS - aged meats/cheese, beer), High toxicity in overdose

Isocarboxazid MoA

MAO-Is (nonselective, IRREVERSIBLE)--> Increased NE, 5-HT, DA in pre-synaptic terminal

Isocarboxazid Tx

Tx Resistant Depression (3rd/4th Tx)

Isocarboxazid S/E

Hypertensive crisis IF NO washout before TCAs, SSRIs, SNRIs added + STRICT DIET (NO TYRAMINE FOODS - aged meats/cheese, beer), High toxicity in overdose

Why are MAO-Is C/I with dietary tyramine?

Blocks deamination --> NE release ==> Fatal increase in BP

Ketamine MoA

NDMA NON-competitive Antagonist (activate new glutamate receptors --> More active neurons)

Ketamine Tx

IV - RAPID; Resistant/Refractory Depression , Resistant/Refractory Depression Anesthetic

Ketamine S/E

"Dissociative Experience" (lasts 2 hrs) --> if used Casually = LOCs, High BP, Dangerous slow breathing + Long Term = Ulcers, Cystitis (pain), Kidney problems, stomach pain, depression, poor memory, ABUSE POTENTIAL

Esketamine MoA

NDMA NON-competitive Antagonist (activate new glutamate receptors --> More active neurons)

Esketamine Tx

NASAL SPRAY - for Agitated pts, Resistant/Refractory Depression; RAPID

Esketamine S/E

"Dissociative Experience" (lasts 2 hrs)

Psilocybin MoA

Active part of "Magic Mushrooms" --> LSD type effects

Psilocybin Tx

Experimental for VERY RAPID Tx of Depression

Psilocybin S/E

Suicidal Ideation in HIGH DOSE (trials)