Depression - Block 3 Flashcards

1
Q

Describe the mechanism of seratonin and melatonin?

A
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2
Q

What does the monoamine hypothesis?

A

Serotonin: obsession and compulsions, ax
Dopamine: Attention, motivation, pleasure
NE: Ax, attention

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3
Q

What are the medications used for depression?

A

Serotonergic: SSRIs: Citalopram, Escitalopram, Sertraline, Paroxetine, Fluoxetine
Noradrenergic: TCA
Dopaminergic: Bupropion
Dual mech: Venlafaxine, Duloxetine, desvenlafaxine -SNRIs
* SSRIs + Bupropion
* Mirtazapine, trazadone, vilazodone, vortioxetine

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4
Q

What SSRI has the longest half-life?

A

Fluoxetine

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5
Q

What is the SSRI MOA?

A

Selectively blocking the reuptake of serotonin to increase the amount of serotonin in the synapse

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6
Q

What are causes of depression?

A
  1. Unknown
  2. ELevated stress levels (genetics)
  3. Decreased levels or activity of NE and/or serotnin/dopamine
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7
Q

What are the main diagnosistic for depression?

A

DSM5 and ICD10

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8
Q

How do you diagnose a patient with depression?

A
  1. Screen patient for hx and psychiattic history
  2. DSM5 for diagnosis
  3. Exclude other potential causes of symptoms
  4. Use clinician rating scale like PHQ-9/ HAM-D/ GDS to determine severity and to set baseline for monitoring purposes
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9
Q

What is PHQ9?

A

Screening tool and aids the diagnosis of depression severity as well as track improvements of sx

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10
Q

What are the common sx of depression?

A

Sleep disturbances
Interest or pleasure is decreased
Guilt or feeling worthless
Mood is low or depressed
ENergy loss or fatigue
Concnetration problems or problems with memory
Appetitie disturbance, weight loss or gain
Psychomotor agitation or retardation
Suicidal ideation, thoughd of death

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11
Q

What is mDD?

A

sx must affect QOL-cause clinically significant disturbances of social, occupational, functioning

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12
Q

Depression must have:

A
  1. Depressed mood a/o anhedonia
  2. Additional symptoms (must total at least 5 for > 2 weeks):
    * Sleep disturbance
    * Changes in appetite or weight
    * Decreased energy
    * Feelings of guilt or worthlessness
    * Psychomotor agitation or retardation
    * Decreased concentration
    * +/- Suicidal ideation
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13
Q

What disease states can be mistaken for depression?

A
  1. CNS disease
  2. Endocrine disorders
  3. Drug-related conditions
  4. SLeep-related disorders
  5. Bipoal
  6. Schizo
  7. Bereavement
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14
Q

What are the drugs that worsen depression?

A

A: Alcohol, amphetamines, ADHD med (withdrawal-likemethylphenidate,amoxeine)
B: BDZ, Barbiturates, B-Blockers(lipid soluble- propranolol)
C: CNS depressants, cocaine

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15
Q

How do you assess for deferential diagnosis?

A
  1. Patient hx ask about:
    * Stressful events
    * Consumption of illicit drugs, alcohol abuse
    * Current medications
    * Current medical conditions
    * Family history of bipolar or schizophrenia
    * Assess severity of symptoms
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16
Q

What are patient assessment tools we can use?

A

PHQ9, HAM-D, MADRS

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17
Q

What is the scoring of HAM-D?

A

Normal: 0-7
Mild: 8-13
Mod: 14-18
Severe: 19-22
Very severe: ≥23

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18
Q

Whay do we look for when evaluating a patient?

A

Suicidal ideation: hosptial should be considered if risk is significant

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19
Q

What are non-pharms for Tx?

A

CBT
Religion
Avoid stress
Excersise
Self-affirmation
Positivity
Motivational speakers

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20
Q

Types of med intervention?

A
  1. Medications
  2. Psychotherapy
  3. ECT
  4. VNS
  5. Combo
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21
Q

What complementary tx is good for depression but has a lot of DDIs?

A

St Johns wort: treatment of adults experiencing major depression of moderate severity
* Serotonergic, cause photosensitivity

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22
Q

How do we select a AD?

A
  1. All AD are equal in effectiveness and safety (anticipated DDI, SE)
  2. Consider prior response
  3. Comorbidities
  4. Presenting symptoms vs target receptors
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23
Q

What is the recommendations for administering an AD?

A
  1. Startlow gradual increase dose; 1-2 wks. to feel better 6-8 wks. For fulleffect
  2. Physical symptoms (energy levels, sleep disturbance) before mood improves- suicide risk
  3. Adequate trial of drug must be provided (4-8 wks) before considering (increase dose, switch, augment, combo)
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24
Q

What is the goal of AD tx?

A
  1. Remission may take 12 wks (HAM-D score of ≤7)
  2. 50% reduction in sx
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25
Q

What is the first line for MDD?

A

SSRI: fluoxetine, sertraline, paroxetine, citalopram, escitalopram, and fluvoxamine

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26
Q

BBW of all AD?

A

Suicidality

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27
Q

Common ADR of AD?

A
  1. N
  2. D
  3. COnstipation
  4. Insomnia
  5. Serotonin syndrome
  6. Sexual SE
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28
Q

SSRI

Counseling points

A
  1. Don’t D/C abruptly must taper to prevent withdrawals
  2. Start low gradual increase dose; 1-2 wks. to feel better 6-8 wks. For full effect
  3. Physical sx before mood improves
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29
Q

How do we manage SSRI-induced sexual SE?

A
  1. Will disappear spontaneously
  2. Dose reduction
  3. Add bupropion
  4. Drug holiday for patients on short-acting SSRI
  5. sildenafil or tadalafil for man, TD testosterone for women
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30
Q

How do we manage SSRI-induced GI SE?

A

N/V/C/D/Gi bleed
1. GI SE wanes after 2 or 3 weeks generally
2. Divide dose
3. Take with food
4. administering more of the dose at bedtime can help
5. Ginger
6. Antidiarrheal or switch to other agents
7. Constipation: physical activity, fluid and fiber intake, or laxatives

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31
Q

Fluoxetine

MOA, Counseling

A

Prozac
MOA: SSRI
Counseling: can cause insomnia and anxiety

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32
Q

Sertraline

MOA, Counseling

A

Zoloft
MOA SSRI
Counseling: Low concentration in breastmilk, causes insomnia and GI se

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33
Q

Paroxetine

MOA, Counseling

A

Paxil
MOA: SSRI
Counseling: Causes constipation, sedation, weight gain
* Teratogenic

34
Q

Fluvoxamine

MOA, Counseling

A

Luvox
MOA: SSRI
Counseling: Sedation

35
Q

What are important counseling points for fluoxetine?

A

Long half-life
* 5 week washout from fluoxetine to MAO
* 2 weeks for others

36
Q

Special considerations of citalopram?

A

QTc prolongation risk if >40 mg
* Max: 40 mg or 20 mg in ≥60YO, hepatic impairment, poor CYP2C19 metabolizers, or meds that inhibit CYP2C19

37
Q

Medication first line for post-partum depression?

A

Sertraline (Zoloft)

38
Q

DDI of fluoxetine and paroxetine?

A

strong CYP 2D6 inhibitors so they increase serum concertation of:
* Metoprolol
* Haloperidol
* Risperidone
* Tamoxifen

Inhibits conversion of tramadol and hydrocodone to their active metabolite

39
Q

DDI of fluvoxamine

A

CYP1A2 inhibitor -> increasce concentration of thioridazine, theophylline, olanzapine, clozapine,ramelteon and phenytoin

40
Q

What is seratonin syndrome?

A

Fatal from use of multiple serotenergic drugs such

41
Q

OTC products that can cause serotonin syndrome?

A

St. John’s wort

42
Q

Drugs that cause serotonin syndrome?

A

T- Triptans , TCA, Tramadol
L- Lithium,Linezolid
S- SNRI, Sympathomimetics
M- MAOI, Meperidine
D- Dextromethorphan

43
Q

What is the tx for serotonin syndrome?

A
  1. DC offending agent
  2. Supportive: cooling blankets and respiratory assistance
  3. Clonazepam for myoclonus
  4. Anticonvulsants for sz
  5. Nifedipine for HTN
44
Q

What is activation syndrome?

A

early worsening of anxiety, agitation, and irritability that occurs in patients starting serotonergic or noradrenergic antidepressant

45
Q

Tx for activation syndrome?

A
  1. DC Tx
  2. Patient ed
  3. slower titration, especially in patients with anxiety symptoms, might prevent the syndrome
  4. jitteriness is time-limited, waiting for tolerance to develop or temporarily combining the antidepressant with a benzodiazepine or propranolol may be helpful
46
Q

What is DC syndrome?

A

Develops 1-7 days following dose reduction or DC of SNRI or SSRI

47
Q

Tx for DC syndrome?

A
  1. Tailor tapering to individual patient and specific antidepressants
  2. Gradual reduction over 2-4 weeks
  3. Prescribing and long-acting SSRI (fluoxetine) with DC current AD
48
Q

What are the main sx of SC syndrome?

A

Flu like sx
Insomnia
Nausea
Imbalance
Sensory distrubances
Hyperarousal

49
Q

SSRI used for GAD?

A

Escitalopram

49
Q

What SSRI is used for OCD and not for really for depression?

A

Fluvoxamine

50
Q

Types of SNRI?

A

venlafaxine, duloxetine, and desvenlafaxine

51
Q

SNRI ADR?

A
  1. Dry mouth
  2. Sexual dysfunction
  3. Sweating
  4. COnstipation
  5. Increased BP
  6. Insomnia
52
Q

What are the advantages of using duloxetine? CI?

A

Chronic pain, neuropathic pain, fibromyalgia, musculoskeletal pain
CI: narrow angle glaucome or liver or kidney dx, alcoholics
* Liver Damage

53
Q

What SNRIs cause increased BP?

A

Venlafaxine and desvenlafaxine: Causes HTN

54
Q

What are the other indications of duloxetine other than depression?

A

Diabetic peripheral neuropathy
Fibromyalgia
Chronic musculoskeletal pain

55
Q

DDI of both SSRI and SNRI?

A
  • Increased bleeding with anticoags, antiplatelet, NSAIDs, gingko
  • HTN crisis when given with MAO-I (14 day wash out)
56
Q

DDI of MAOI?

A
  • Tyramine foods wih MAOI can lead to HTN crisis (aged, fermented, beans)
  • OTC decongestants
57
Q

What is the washout preriod between MAOS and starting other AD or CI drugs?

A

2 week break

58
Q

ADR of MAOI?

A
  • Orthostatic hypotension
  • HTN crisis
  • Drowsiness
  • DZ
  • Insomnia
  • Sexual dysfunction
  • Birth defects
59
Q

What are the MAOIs?

A

phenelzine, isocarboxazid, tranylcypromine, and selegiline

60
Q

What MAOI can be given with tyramine?

A

transdermalselegiline(Emsam)

61
Q

What are the off-label uses for TCAs?

A

Migraine prophylaxisis
Pain and ax disorders

62
Q

TCA used for migraine prophylaxis?

A

Nortriptyline, amitriptyline

63
Q

TCA used for neuropathic pain?

A

Nortriptyline, amitriptyline

64
Q

TCA used of insomnia?

A

DOxepin

65
Q

What are limitations of using TCA?

A
  1. Naroow TI
  2. Slow onset
  3. Significant ADR
  4. Cardiotoxic and potentially fatal OD
    * SZ and torsades risk
    * Increased suicidicity
66
Q

What are the prominent ADRs of TCAs?

A

ANTI-HAM
Antihistamine-sedation, weight gain
Anti- alpha adrenergic -orthostatic hypotension,cardiac abnormalities, sexual function
Anti-muscarinic –dry mouth, tachycardia,urinaryretention , blurry vision, constipation
Anticholinergic
Orthostatic
Withdrawal: if DCd abruptly

67
Q

What are the atypical AD?

A
  1. Trazadone
  2. Bupropion
  3. Mirtazapine
  4. Clomipramine
  5. Vilazodone

Last line, for patients with resistant depression

68
Q

Mirtazapine

MOA, ADR, BBW

A

MOA: alpha 2 receptor antagonist, antagonist of 5-HT2, 5-HT3, and muchhistamine-1 (H1) receptors
ADR: sedation, increased appetite, weight gain
BBW: hepatotoxicity

69
Q

Bupropion

Advantages, ADR

A

Advantages: Less sexual dysfunction (or improve sexual function)
* 25% of patients experience initial weight loss

ADR: Insomnia (take in AM), ax, psychosis, seizure risk

70
Q

Trazadone

ADR

A

As effective as TCA and SSRI
ADR: priapism

71
Q
A
72
Q

How do we choose the righ AD?

A
  1. All antidepressants are equally efficacious
  2. Fit med to patient based on sx, hx, comorbid, cost, preference, ADR, meds
73
Q

What are is the order of AD selection?

A

First SSRIs,then SNRIs can consider Bupropion, Mirtazapine

74
Q

When should we assess the response to AD?

A

correct drug, dose, duration in 6 to 8 weeks

75
Q

What are the types of augmentation tx?

A

Aripiprazole
Quetiapine ER
Olanzapine+fluoxetine(symbyax)
Buspirone
Lithium

76
Q

What is resistant depression?

A

If patient fails to achieve remission after ≥2 antidepressants(same or different class),of adequate dosage and duration =Treatment resistance depression

77
Q

What are the approaches for resistant depression?

A
  1. treatment is considered failed with 6-8 week trial
  2. First try dose increase
  3. 2nd combine antidepressants with different MOA
  4. Augmentation therapy
78
Q

What medication is indicated for resistant depression?

A

Olanzapine in combination with fluoxetine

79
Q

Overall counseling for AD?

A
  1. Takes about 1-2wks to feel better 6 to 8 weeks to see full effect
  2. continue to take their medications regularly as directed, even if their symptoms are less noticeable or have resolved
  3. Must be used daily not prn, continue to take even if you feel well
  4. Do not D/C abruptly- to prevent rebound depression esp. Paxil
  5. Talk to pharmacist or MD before starting any medication including herbal or OTC