Depression Flashcards
What are the causes of Depression?
-Genetic (family history)
-Environmental (Substance abuse, trauma, stress, chronic health problems etc)
What are the major Neurotransmitters in Depression?
- Serotonin (major)
- Norepinephrine
- Epinephrine
- Dopamine
- Glutamate
- Acetylcholine
What are some natural products for the treatment of depression?
1) St. John’s Wort
2) S-adenosyl-L-methionine (SAMe)
3) Valerian Root
What classes of medication is used to treat Depression?
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.
What are the Boxed Warnings for Antidepressants?
Antidepressants increases the risk of suicidal thoughts and behavior in pediatric and young adult patients.
Tapering Antidepressants
-Do not abruptly stop antidepressants
-Taper over several weeks
-Exception: Fluoxetine because of long half-life
How do SSRI’s work?
Selective serotonin receptor reuptake inhibitors increase serotonin by inhibiting its reuptake in the synapse.
What are the major SSRI’s?
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!
What are the Class contraindications of SSRIs and SNRIs?
1) DO NOT use with MAO Inhibitors, Linezolid, IV methylene blue
What SSRI have warnings for QT Prolongation?
1) Citalopram:
Max 40 mg/day
Max for elderly 20 mg/day
2) Escitalopram
Max 20 mg/day
Max for elderly 10 mg/day
What are the Class side effects of SSRIs and SNRIs?
1) Sexual: low libido, functional problems
2) CNS Effects: somnolence, insomnia, dizziness, headache, weakness and tremor
3) Nausea, dry mouth
What are the combined mechanism drugs?
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.
How do SNRIs work?
These inhibit the reuptake of serotonin and norepinephrine in the synapse
What are the main SNRIs?
1) Venlafaxine (Effexor XL)
2) Duloxetine (Cymbalta)
3) Desvenlafaxine (Pristiq)
What are the side effects of SNRIs?
Same as SSRIs
Additional effects due to increased norepinephrine:
-Increase blood pressure
-Increase heart rate
-Dilated pupils
-Dry mouth
-Excessive sweating
-Constipation
Reactions when using SSRIs or SNRIs
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
How do Tricyclic Antidepressants work?
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.
What are the TCAs?
1) Amitriptyline
2) Nortriptyline (Pamelor)
3) Clomipramine
4) Desipramine
5) Doxepin
What are the contraindications of TCAs?
DO not use with MAOI, Linezolid or IV methylene blue
What are the side effects of TCAs?
1) Cardiotoxicity:
-QT Prolongation
-Orthostatic hypotension
2) Anticholinergic:
-Dry Mouth
-Blurry vision
-Urinary retention
-Constipation
-Weight gain
How do Bupropion work?
This medication blocks the reuptake of dopamine and norepinephrine. (Not serotonin)
Brand: Wellbutrin
Contraindication of Bupropion
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
Notable side effects of Bupropion
-Dry mouth
-Insomnia, restlessness
-Weight loss*
-Sexual dysfunction is rare*
How do MAOI work?
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.
What are the main MAOI?
NONSELECTIVE:
1) Tranylcypromine (Parnate)
2) Phenelzine (Nardil)
3) Isocarboxazid (Marplan)
MAO-B SELECTIVE
4) Selegiline (Patch is for depression, ODT is for Parkinson’s)
Contraindications of MAOI
1) History of CV disease, Cerebrovascular defect, headache, hepatic disease, pheochromocytoma
2) Do not use with other sympathomimetics
3) Severe renal disease
Warnings of MAOI
Hypertensive crises or serotonin syndrome can occur when taken with TCAs, SSRIs, SNRIs and tyramine-rich foods.
Drug interactions of MAOI
1) Antidepressants (TCA, SNRI, SSRI), Bupropion)
2) Amphetamines/Stimulants
3) Linezolid
4) Methylene Blue
5) Tyramine-rich foods
What are tyramine-rich foods?
Aged, fermented, pickled, smoked foods
e.g. Aged cheese, cured, smoked or processed meats, pickled or fermented foods, soy sauce, beer
What are products that increase serotonin?
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
How can we avoid serotonin syndrome or hypertensive crises?
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.
What are some miscellaneous antidepressants with some novel mechanisms?
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.
Best antidepressant for Cardiac issues/ QT risk
Sertraline
-Avoid high doses of Citalopram and Escitalopram
Best antidepressant for Smoking cessation
Bupropion is indicated for both
Best antidepressant for peripheral neuropathy
Duloxetine is indicated for both
Best antidepressant for use with history of seizures
Avoid bupropion
Antidepressant to avoid in pregnancy
Paroxetine
-SSRI is preferred to be used in pregnancy.
Antidepressant for issues with sexual dysfunction
SSRI and SNRI have higher risk
Bupropion and Mirtazapine have lower risk
What is Treatment-Resistant Depression?
This is depression that does not improve following 2 full treatment trials (1 trial ~ 4-8 weeks)
How to treat Treatment-Resistant Depression?
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
