IC12 Mood disorder I - Depression Flashcards
What is SSRIs and what are they used for?
SSRIs - serotonin reuptake inhibitor
They inhibit the reuptake of serotonin.
SSRIs are used as 1st line agents for depression and anxiety.
List out common SSRIs that we know
- Escitalopram
- Fluoxetine
- Sertraline
- Citalopram
- Paroxetine
What common ADRs of using SSRIs?
- Drowsiness / insomnia, N&V
- Bleeding risk
- Hyponatremia
- Serotonin syndrome
- Sexual dysfunction
What are the 4 main challenges in the use of SSRIs?
- Drug response differs from every individual
- SSRIs have delayed onset - we can only determine the response after 4-8 weeks
- ADRs
- DDIs
Which are the 2 most common CYP enzymes involved in metabolism of SSRIs?
- CYP2D6
- CYP2C19
CYP2D6 & CYP2C19 help to metabolise SSRIs into inactive* metabolites.
Individuals with poor metabolizing gene for CYP2D6 and CYP2C19 will experience greater ADRs.
What kind of pharmacogenetics testing should we do for patients with inadequate response or have adverse reactions to SSRIs?
- We should consider CYP2D6 and CYP2C19 genotyping in patients with inadequate response or have adverse reactions.
How should we adjust dosing for drugs that are affected by CYP2D6 and CYP2C19 genotypic variation:
- Rapid metabolizers
- Intermediate metabolizers
- Poor metabolizers
Rapid metabolizers - increase dose of SSRI
Intermediate metabolizers - no change to dosing in SSRIs , except paroxetine which is to be decreased
Slow metabolizers - decrease dose of SSRI
Which SSRIs metabolism are affected by CYP2C19 genotypic variation?
Escitalopram, Sertraline, Fluvoxamine
Which SSRIs metabolism are affected by CYP2D6 genotypic variation?
Fluoxetine, paroxetine, bupropion
(six has an X in its spelling. SSRIs with X in its spelling are affected by CYP2D6)
What are general risk factors of depression?
- Poor
- Old
- Loneliness
- Male
- Other comorbidities
- History of attempted suicide
What are red flags for a patient with depression?
- Suicidal ideation
- Has a suicide plan
- Possess an intent to carry out the plan
- Exploring reasons to live and die
We should ask all patients w depression if they have any actual thoughts of killing themselves
What is the main theory that is speculated to cause Major Depressive Disorder (MDD)?
The Monoamine Hypothesis Theory
This theory talks about ↓ levels of:
(1) Norepinephrine (NE)
(2) Serotonin (5-HT)
(3) Dopamine (DA)
Apart from the Monoamine Hypothesis Theory, there are other contributing factors that can cause depression.
These factors are known as secondary causes.
What are some 3 examples of secondary causes?
- Medical
- *Endocrine disorder: hypothyroidism
- *CV: Coronary artery disease, CHF, MI - Psychiatric disorders
- Alcoholism
- Schizophrenia
- Anxiety disorder
- Eating disorder - Drug induced
- Beta blockers
- Withdrawal from alcohol, or other stimulants
- Corticosteroids
- CNS depressants: Benzodiazepine, barbiturates, opioids
The acronym for the clinical presentations of MDD is:
In. SAD. CAGES
What does In. SAD. CAGES stand for?
In - Interest
S - Sleep
A - Appetite
D - Depressed
C - Concentration
A - Activity
G - Guilt
E - Energy
S - Suicidal thoughts or attempts***
What is the guideline to diagnose a patient with MDD?
- Present at least 5 symptoms of IN.SAD.CAGES x 2 weeks
- Symptoms cause significant distress or impairment
- Symptoms are not caused by an underlying medical condition
In.SAD.CAGES:
In - Interest
S - Sleep
A - Appetite
D - Depressed
C - Concentration
A - Activity
G - Guilt
E - Energy
S - Suicidal thoughts or attempts***
Major Depressive Disorder (MDD), Adjustment disorder, Acute Stress disorder are 3 different disorders.
What are the differences between the 3 disorders?
MDD presents ≥ 5 out of 9 In.SAD.CAGES S&S for 2 weeks
Adjustment disorder is a temporary onset of depression sx within 3 months of a stressor. Once stressor is eliminated, sx of depression goes away.
Acute stress disorder is a temporary onset of depression within 1 month of a stressor.
Both Adjustment disorder and Acute stress disorders are very similar.
The difference between adjustment disorder and acute stress disorder is that:
- Adjustment disorder occur within 3 months
- Acute stress disorder occurs within 1 month
What should we screen in patients before initiating antidepressants?
It is mandatory that we screen if a patient has mania, before we administer antidepressants.
Mania is a red flag that we must rule out.
Ask patient if they have any history of manic / hypomanic episode
What are the 3 D’s?
- Delirium
- Dementia
- Depression
The 3 D’s are often confused with one another.
What is the difference between the 3 D’s
- Delirium
- Dementia
- Depression
Based on (1)Onset, (2)Consciousness, (3)Memory
Onset:
> Delirium - acute
> Dementia - gradual
> Depression - cyclical
Consciousness:
> Delirium - impaired
> Dementia - clear until later stages
> Depression - generally unimpaired
Memory:
> Delirium - poor
> Dementia - poor short & long-term
> Depression - intact
The Hamilton Rating scale for Depression (HAM-D) is the GOLD standard assessment for measuring severity of depression.
What score on the HAM-D scale would a patient achieve remission from depression?
A patient with a score of ≤7 will be able to achieve remission from depression.
What is the main class of medication to use in MDD?
Antidepressants.
There are 4 types of anti-depressants:
1. *Mirtazapine (1st line)
2. *SSRI
3. SNRI
4. Bupropion
There are 2 phases of treatment for MDD:
- Acute phase treatment
- Continuation phase treatment
What does these 2 phases of treatment mean?
- Acute phase treatment:
- Treatment for 4-8 weeks
- Adequate dose is used - Continuation phase:
- Treatment for 4-9 months after acute phase treatment
- Total duration including acute phase treatment is between 6-12 months at least
Antidepressants do not work immediately. Physical symptoms may improve in 1-2 weeks, while mood symptoms take longer to improve (4 - 8 weeks).
What are the antidepressant medications that we must know?
- SSRI - Fluoxetine, fluvoxamine, escitalopram
- SNRI - venlafaxine, duloxetine
(Duloxetine can be used for chronic muscular pain as well) - Mirtazapine
There are other classes of antidepressants - such as TCAs, MAOIs and Bupropion
What are the SE of:
1. SSRIs
2. SNRI
3. Mirtazapine
4. TCA
5. MAOI
6. Bupropion
- SSRI - GI & sexual dysfunction
- SNRI - GI & sexual dysfunction
- Mirtazapine - sedation & weight gain (Reverses GI & Sexual SE of SSRI & SNRI)
- TCA - GI & sexual dysfunction, anticholinergic, fatal on overdose, sedation, weight gain, orthostatic hypotension
- MAOI - hypertensive crisis
- Bupropion - ↑ risk of seizures
Don’t use TCAs unless it is a last resort option.
All antidepressants are associated w causing hyponatremia.
What are some non-pharmacological therapy for depression?
- Sleep hygiene
- Exercise
- Avoid use of St John’s Wort if on antidepressants
What are some rules that we must follow if we need to swap antidepressants in patient?
- Switching SSRI w SNRI
- Switching SSRI w SSRI
- Switching from SSRI/SNRI to bupropion
- Switching from MAOI to SSRIs
- Switching SSRI w SNRI
- Can switch directly and immediately - Switching SSRI w SSRI
- Can switch directly - Switching from SSRI/SNRI to bupropion
- Requires gradual cross-tapering over several weeks - Switching from MAOI to SSRIs
- Wash out period is necessary for MAOIs
If ≥2 adequate trials of antidepressants still have no effects, consider using combination therapy
What are some DDIs involving antidepressants?
- SSRI/SNRI + SSRI/SNRI = ?
- SSRI & bleeding medications = ?
- Alcohol + CNS depressants = ?
- Anticholinergic agents + antidepressants = ?
- SSRI/SNRI + SSRI/SNRI = Serotonin syndrome
- SSRI & bleeding medications = High bleeding risk
- SSRIs ↑ risk of bleeding - Alcohol + CNS depressants = ↑ CNS depressant effects
- Anticholinergic agents + antidepressants = excessive anticholinergic effects
What CYP enzymes do these drugs/drink inhibit?
- Fluvoxamine
- Fluoxetine
- Paroxetine
- Bupropion
- Grapefruit juice
- Mirtazapine
- Fluvoxamine - CYP1A2, CYP2C19
- Fluoxetine - CYP2D6
- Paroxetine - CYP2D6
- Bupropion - CYP2D6
- Grapefruit juice - CYP3A4
- Mirtazapine - little to no CYP enzyme interactions
What is Antidepressant Discontinuation Syndrome (ADS)?
ADS is a sudden discontinuation of antidepressants, which leads to development of symptoms.
ADS is NOT withdrawal.
Some Sx of ADS:
1. Flu-like symptoms
2. Insomnia
3. N&V
ADS can be avoided by gradually tapering and reduce the dose.
What are some counselling pointers when initiating pt on antidepressants?
- Antidepressants may take at least a couple of weeks to work
- Do not take w alcohol. Space 4-6 hours apart.
- If condition is worsening, you feel suicidal, or SE are intolerable, contact your doctor immediately
