Depression

Question 1

What are the causes of Depression?

Answer 1

-Genetic (family history)
-Environmental (Substance abuse, trauma, stress, chronic health problems etc)

Question 2

What are the major Neurotransmitters in Depression?

Answer 2

• Serotonin (major)
• Norepinephrine
• Epinephrine
• Dopamine
• Glutamate
• Acetylcholine

Question 3

What are some natural products for the treatment of depression?

Answer 3

1) St. John’s Wort
2) S-adenosyl-L-methionine (SAMe)
3) Valerian Root

Question 4

What classes of medication is used to treat Depression?

Answer 4

1) SSRI or SNRI (first-line) for 4-8 weeks (trial for med to work) - if there is no response after this time, increase, switch or add to this.

*Psychotherapy is preferred in mild depression, but is used as add-on for all ranges of depression.

*SSRI is preferred in pregnancy. NO paroxetine in pregnancy, due to cardiac effects.

Question 5

What are the Boxed Warnings for Antidepressants?

Answer 5

Antidepressants increases the risk of suicidal thoughts and behavior in pediatric and young adult patients.

Question 6

Tapering Antidepressants

Answer 6

-Do not abruptly stop antidepressants
-Taper over several weeks
-Exception: Fluoxetine because of long half-life

Question 7

How do SSRI’s work?

Answer 7

Selective serotonin receptor reuptake inhibitors increase serotonin by inhibiting its reuptake in the synapse.

Question 8

What are the major SSRI’s?

Answer 8

1) Citalopram (Celexa)
2) Escitalopram (Lexapro)
3) Fluoxetine (Prozac) - long half-life
4) Paroxetine (Paxil)
5) Sertraline (Zoloft)

*Sertraline is preferred in patients with cardiac risk!

Question 9

What are the Class contraindications of SSRIs and SNRIs?

Answer 9

1) DO NOT use with MAO Inhibitors, Linezolid, IV methylene blue

Question 10

What SSRI have warnings for QT Prolongation?

Answer 10

1) Citalopram:
Max 40 mg/day
Max for elderly 20 mg/day

2) Escitalopram
Max 20 mg/day
Max for elderly 10 mg/day

Question 11

What are the Class side effects of SSRIs and SNRIs?

Answer 11

1) Sexual: low libido, functional problems

2) CNS Effects: somnolence, insomnia, dizziness, headache, weakness and tremor

3) Nausea, dry mouth

Question 12

What are the combined mechanism drugs?

Answer 12

1) Vilazodone (SSRI + 5-HT1A partial agonist)

2) Vortioxetine (SSRI + 5-HT3 antagonist + 5-HT1A agonist

*However, these appear to have fewer sexual side effects.

*These additional Mechanisms do not mean that they work better than the SSRIs.

*We would normally recommend a generic SSRI before recommending these, mainly due to cost.

Question 13

How do SNRIs work?

Answer 13

These inhibit the reuptake of serotonin and norepinephrine in the synapse

Question 14

What are the main SNRIs?

Answer 14

1) Venlafaxine (Effexor XL)
2) Duloxetine (Cymbalta)
3) Desvenlafaxine (Pristiq)

Question 15

What are the side effects of SNRIs?

Answer 15

Same as SSRIs

Additional effects due to increased norepinephrine:
-Increase blood pressure
-Increase heart rate
-Dilated pupils
-Dry mouth
-Excessive sweating
-Constipation

Question 16

Reactions when using SSRIs or SNRIs

Answer 16

1) Serotonin syndrome or hypertensive crisis - use a 2 week washout from MAOI
[Same with TCAs and MAOI]
[Same with Bupropion and MAOI]

2) QT prolongation - noted with citalopram and escitalopram, additive risk with venlafaxine.

3) Additive bleeding risk - when used with anticoagulants, antiplatelets, NSAIDs, fish oils

Question 17

How do Tricyclic Antidepressants work?

Answer 17

TCAs primarily block norepinephrine and serotonin reuptake, but they also block Ach and histamine receptors.

This gives them their Ach side effects.

The histamine aspect makes them more sedating.

Question 18

What are the TCAs?

Answer 18

1) Amitriptyline
2) Nortriptyline (Pamelor)
3) Clomipramine
4) Desipramine
5) Doxepin

Question 19

What are the contraindications of TCAs?

Answer 19

DO not use with MAOI, Linezolid or IV methylene blue

Question 20

What are the side effects of TCAs?

Answer 20

1) Cardiotoxicity:
-QT Prolongation
-Orthostatic hypotension

2) Anticholinergic:
-Dry Mouth
-Blurry vision
-Urinary retention
-Constipation
-Weight gain

Question 21

How do Bupropion work?

Answer 21

This medication blocks the reuptake of dopamine and norepinephrine. (Not serotonin)

Brand: Wellbutrin

Question 22

Contraindication of Bupropion

Answer 22

Contraindicated in:
1) Seizure disorder, since bupropion can lower the seizure threshold. MAX 450 mg/day

2) Bulimia, Anorexia

3) MAOI, Linezolid, IV methylene blue

Question 23

Notable side effects of Bupropion

Answer 23

-Dry mouth
-Insomnia, restlessness
-Weight loss*
-Sexual dysfunction is rare*

Question 24

How do MAOI work?

Answer 24

Monoamine oxidase inhibitors inhibit the enzyme monoamine oxidase, which breaks down the catecholamines (serotonin, norepinephrine, epinephrine and dopamine)

If these neurotransmitters increase dramatically, hypertensive crises and death can occur.

Question 25

What are the main MAOI?

Answer 25

NONSELECTIVE:
1) Tranylcypromine (Parnate)
2) Phenelzine (Nardil)
3) Isocarboxazid (Marplan)

MAO-B SELECTIVE
4) Selegiline (Patch is for depression, ODT is for Parkinson’s)

Question 26

Contraindications of MAOI

Answer 26

1) History of CV disease, Cerebrovascular defect, headache, hepatic disease, pheochromocytoma

2) Do not use with other sympathomimetics

3) Severe renal disease

Question 27

Warnings of MAOI

Answer 27

Hypertensive crises or serotonin syndrome can occur when taken with TCAs, SSRIs, SNRIs and tyramine-rich foods.

Question 28

Drug interactions of MAOI

Answer 28

1) Antidepressants (TCA, SNRI, SSRI), Bupropion)
2) Amphetamines/Stimulants
3) Linezolid
4) Methylene Blue
5) Tyramine-rich foods

Question 29

What are tyramine-rich foods?

Answer 29

Aged, fermented, pickled, smoked foods
e.g. Aged cheese, cured, smoked or processed meats, pickled or fermented foods, soy sauce, beer

Question 30

What are products that increase serotonin?

Answer 30

1) Antidepressants
2) Linezolid
3) Lithium…
4) Opioids…
5) St. John’s Wort
6) Tramadol…

*When these are used concurrently with antidepressants, they increase the risk of developing serotonin syndrome

Question 31

How can we avoid serotonin syndrome or hypertensive crises?

Answer 31

Use a 2-week washout with SSRI, SNRI, TCA, Bupropion.

Since fluoxetine has a long half-life, use a 5-week washout when switching to a MAOI.

Question 32

What are some miscellaneous antidepressants with some novel mechanisms?

Answer 32

1) Mirtazapine (Rameron)….
2) Trazodone….
3) Nefazodone

-Mirtazapine and Trazodone have sedating side effects.
-Trazodone is mainly used off-label for sleep.
-Mirtazapine is mainly used off-label for increasing appetite, and for sleep.

Question 33

Best antidepressant for Cardiac issues/ QT risk

Answer 33

Sertraline

-Avoid high doses of Citalopram and Escitalopram

Question 34

Best antidepressant for Smoking cessation

Answer 34

Bupropion is indicated for both

Question 35

Best antidepressant for peripheral neuropathy

Answer 35

Duloxetine is indicated for both

Question 36

Best antidepressant for use with history of seizures

Answer 36

Avoid bupropion

Question 37

Antidepressant to avoid in pregnancy

Answer 37

Paroxetine

-SSRI is preferred to be used in pregnancy.

Question 38

Antidepressant for issues with sexual dysfunction

Answer 38

SSRI and SNRI have higher risk
Bupropion and Mirtazapine have lower risk

Question 39

What is Treatment-Resistant Depression?

Answer 39

This is depression that does not improve following 2 full treatment trials (1 trial ~ 4-8 weeks)

Question 40

How to treat Treatment-Resistant Depression?

Answer 40

1) Increase dose of existing antidepressant
2) Change to a different antidepressant
3) Use a combination of antidepressants with different mechanisms
4) Augment with:
-Buspirone
-Atypical antipsychotic
-Lithium
-Esketamine

*Atypical antipsychotics include: Aripiprazole (Abilify), Olanzapine/fluoxetine, Quetiapine (Seroquel), Brexpiprazole