Antidepressants

Response

> 50% improvement in symptoms, the patient is better but not well.

Remission

All symptoms are gone but for < 6mo

Recovery

Remission lasting longer than 6mo.

Relapse

Depression comes back before full remission or after remission

Recurrence

A new episode after the person has fully recovered

What is the modern goal of antidepressants

Full remission

Who is the rate of relape in MDD better for?

Someone who has acheived full remission

Explain this image

When an antidepressant is introduced, monoamines increase quickly, but theraputic effects in receptor sensitivy take longer

Explain the Neurotransmitter-Receptor Hypothesis

A NT blocks the reuptake in the syanpse which causes increased NT causing receptor downregualtion

What does an SSRI do?

Blocks SERT which causes increase SER in synaptic cleft

What is the actions that causes the theraputic effects of SRRIs

5HT is blocked at the soma and denderites. This causes incraeses SER and action potentials, this causes postsynaptic autoreceptor downregualtion and this is the theraputic effects of SSRIs

What SSRI is this?

Fluoxetine

Who is Fluoxetine best for?

Low mood and low energy depressed patients

Who is fluoxetine worst for?

Agitated and anxioud patients, insomia and panic disorder patients

Is Fluoxetine generally activating or inhibiting

Activating

How does blocking 5HT2C work in Fluoxetine

5HT2C binds to inhibiting GABA interneurosn which frees up the release of DA and NE

What SSRI has the longest half life and minimal withdrawl

Fluoxetine

Fluoxetine side effects

Sexual Dysfucntion

Decreased apetite

Insomnia

SIADH In adults

Which SSRI is this?

Sertraline

Who is Sertaline best for?

Any anxiety disorder patients (OCD, PTSD, GAD)

What are the mechanisms of Sertraline

SERT Inhibition

Weak DAT Inhibition

Sigma-1 binding

What drug should you start ‘low and slow for’

Sertraline

Which SSRI is this?

Citalopram

What is the mechanism of Citalopram

Pure SERT Inhibition of S and R enantiomer

What is the biggest risk with Citalopram

QTc prolongation

What SSRI do elderly commonly use

Citalopram

Which SSR is this?

Escitalopram

Which SSRi only contains the S-enantiomer

Escitalopram

What is considered the best tollerated SSRI on the market?

Escitalopram

Why is Escitalopram the best tolerated?

Removes the antihistamin effect, Only s-enantiomer means now QTc and pure SERT inhibition

Which antidepressant is a SARI

Trazodone?

Why, and what side effects, does trazodone avoid?

Through blocking 5HT2A/C it avoids sexual dysfucntion, insomania, and anxiety

What is trazadone (low doses) clinically commonly used for?

Insomnia

What is Trazodone at higher doses used for?

Antidepressant action

How do you get the theraputic effect for Trazadone?

Blocking 5HT2A/C means you stimulate 5HT1A (theruptic effect)

Which antidepressant works by blocking 5HT2A/C to therefore stimulate 5HT1A for MDD improvment?

Trazadone

Inhibiting which MOA has the theraputic effect?

MOA-A (or both)

How does MOA-A have a theraputic effect?

This blocks monoamine oxidase A, which inhibits MOA-A meaning that more monoamines are avaliable inside the enzyme.

Why are MOA’s not taken alot?

Dietary restrictions (Tyramine problem)

What do TCA’s do

SSRI effect with ‘bagage'

What does H1, M1 and a-1 blockage from TCAs cause

H1 = weight gain and sedation

M1 = dry mouth constipation

a-1 = dizziness

What is the biggest risks for TCA’s

Sodium channel blockage can cause death (heart issues)

What is Ketamines mechanism of action?

It blocks NMDA receptors which inhibits glutamate and causes AMPA receptors to fire which leads to a signal cascade and increased synaptic plasticity

What pathway does Ketamine also affact?

mTOR pathway where it is activated and causes synaptogenisis

What is the antidepressant dose of Ketamine?

0.5 mg/kg - 1.0mg/kg IV