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Major Depressive Disorder (MDD) Flashcards

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1
Q

What are the types of depressive disorder?

A
  • Major Depressive Disorder
  • Persistent Depressive Disorder
  • Substance/Medication-Induced Depressive Disorder
  • Premenstrual Dysphoric Disorder
  • Depressive Disorder due to another medical condition
  • Other specified depressive disorder
  • Unspecified depressive disorder
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2
Q

What are the DSM-5 Criteria for Major Depressive Disorder?

A

Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning

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3
Q

What are the symptoms of Major Depressive Disorder?

A
  • Depressed mood
  • Sleep
  • Interest
  • Guilt
  • Decreased energy
  • Decreased concentration
  • Appetite (weight loss or weight gain)
  • Psychomotor changes
  • Suicidal thoughts
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4
Q

What are medications that can induce major depressive disorder?

A
  • Acyclovir
  • Alcohol
  • Antiepileptic medication
  • Antiretrovirals
  • Barbiturates
  • BB/CCB
  • Corticosteroids
  • Interferon-a & b
  • Isotretinoin
  • Levonorgestrel implants
  • Montelukast
  • Opioids
  • Varenicline
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5
Q

What is the onset of MDD?

A
  • Late 20’s but first episode can develop at any age
  • Can develop over days to weeks or suddenly
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6
Q

What is the duration of MDD?

A
  • Median time to recovery is 20 weeks with adequate treatment
  • 15% of patients never achieve remission (chronic depression)
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7
Q

What is the recurrence of MDD?

A
  • 50% with a single episode will recover without recurrence
  • Risk of recurrence increases with number of episodes
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8
Q

Remission

A

Absence of depressive symptoms or only 1 or 2 symptoms to a mild degree of > 2 months

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9
Q

Monoamine Hypothesis

A

Depressive symptoms related to deficiencies in serotonin (5-HT), Norepinephrine (NE), and Dopamine (DA)

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10
Q

Dysregulation Hyopthesis

A

Depression results from dysregulation of neurotransmitters that leads to alteration in pre & post receptors

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11
Q

Neuroendocrine Hypothesis

A

Dysregulation of thyroid and HPA axis results in sustained in sustained depression

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12
Q

What is the mechanism of action SSRIs?

A

Inhibit the reuptake of serotonin (5HT) in the presynaptic neuron of the CNS–> increased serotonin in the synaptic cleft

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13
Q

SSRI

A
  • First line treatment for MDD
  • Well tolerated
  • Low risk of toxicity
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14
Q

What is the CYP450 metabolism of fluoxetine?

A

2D6

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15
Q

What is the CYP450 Metabolism of fluvoxamine?

A
  • 1A2
  • 2C19
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16
Q

What is the CYP450 metabolism of paroxetine?

A

2D6

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17
Q

What is the longest half-life SSRI?

A

Fluoxetine (norfluoxetine: ~4-6 days)

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18
Q

What are the adverse effects of SSRIs?

A

Common:
* Nausea and/or vomiting
* Headache
* Sleep changes
* Increased in anxiety/agitation or sedation

Serious:
* Hyponatremia
* Increased bleeding/bruising
* Serotonin syndrome

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19
Q

List the SSRIs from most actvivating to most sedation

A
  • Fluoxetine
  • Setraline
  • Escitalopram & citalopram
  • Fluvoxamine
  • Paroxetine
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20
Q

What are some clinical pearls of citalopram?

A
  • Max daily dose not to exceed 40 mg (QTc prolongation)
  • Lower max dose of 20 mg is recommended for elderly (> 60 years), significant hepatic impairment, interacting medications
  • Sedating
  • Starting dose can also be maintenance dose
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21
Q

What is the clinical pearl of escitalopram?

A
  • Also has a risk of QTc prolongation, but no boxed warning
  • Starting dose can also be maintenance dose
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22
Q

What are the clinical pearls of fluoxetine?

A

Longest half life (1-3 days) with longer half life for metabolite (4-16 days)

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23
Q

What are the clinical pearls of setraline?

A

Non-selective–> can affect serotonin in gut and cause more diarrhea and nausea

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24
Q

What are the clinical pearls of fluvoxamine?

A
  • OCD, NO FDA approval in depression
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25
What are the clinical pearls of Paroxetine?
* "Dirtiest SSRI" (anticholinergic & histaminic, more sexual dysfunction) * Most weight gain * Short half-life--> withdrawal
26
What are the clinical pearls of vortioxetine?
Brand only
27
What is the mechanism of action of Serotonin & Norepinephrine Reuptake Inhibitors (SNRIs)?
Inhibits the reuptake of serotonin and norepinephrine presynaptically
28
SNRIs
* Well tolerated * Low risk of toxicity * Additional mechanism (norepinephrine)
29
What is the CYP metabolism Duloxetine (Cymbalta)?
CYP1A2 -Inactive: CYP2D6
30
What is the CYP450 metabolism of Levomilnacipran (Fetzima)?
CYP3A4
31
What are the common side effects of SNRIs?
* Nausea and/or vomiting * Sleep changes * Increased agitation/anxiety * Sexual dysfunction * Dose-dependent blood pressure elevation * Constipation
32
What are the serious adverse effect of SNRIs?
* Hyponatremia * Increased bleed/bruising * Serotonin Syndrome
33
What are the clinical pearls of Venlafaxine?
* Doses > 225 mg/day needed for NE activity, but this dose is also very nauseating * Also inhibits dopamine reuptake at higher doses (>300 mg) * Withdrawal risk high due to half-life, do not use IR formulation
34
What are the clinical pearls of Desvenlafaxine?
* Active metabolite of venlafaxine * Renal dose adjustment needed for CrCl < 50 mL/min * $$$
35
What are the clinical pearls of Duloxetine?
* Contraindicated in hepatic disease * FDA approved for diabetic peripheral neuropathy, musculoskeletal pain, fibromyalgia
36
What are the clinical pearl of Levomilnacipran?
* Brand only, $$$ * Renal adjustment needed for CrCl < 60 mL/min
37
What are the mechanism of action of Serotonin 2 Antagonist/Reuptake Inhibitors (SARIs)?
* 5-HT2A and 5-HT2C receptor antagonist (post-synaptic) * Inhibits serotonin reuptake
38
What are the adverse effects of SARIs?
* Sedation * Dizziness * Orthostatic hypotension * Priapism (rare)
39
What are the clinical pearls of trazodone?
* More commonly used for insomnia than MDD * Doses > 200 mg/day required for treatment of MDD * Doses for insomnia are subtherapeutic for the treatment of MDD
40
What are the clinical pearls of Nefazodone?
* Boxed warning: may cause liver failure * Not first line due to toxicity * Can be used in PTSD
41
What are the mechanism of action of Norepinephrine & Dopamine Reuptake Inhibitor (NDRI)?
Inhibits the reuptake of norepineprhine and dopamine
42
NDRIs
* First or second line treatment of MDD
43
What are the adverse effects of NDRIs?
* Activation (insomnia, agitation, tremor) * Weight loss * Headache * Nausea/vomiting/constipation
44
What are the clinical pearls of NDRIs?
* Beneficial: Fatigue, poor concentration, smoking cessation interest * Contraindicated: Bulimia, anorexia, seizure disorder * Appetite suppression * Lowers the seizure threshold * Activating
45
What is the mechanism of action of the Noradrenergic & Specific Serotonergic Antidepressant (NaSSa)
* Primary--> alpha 2 agonist * Secondary--> 5-HT2A, 5-HT2C, and 5-HT-3 antagonist, antihistamine
46
NaSSa
* Considered as a second line agent
47
What are the clinical pearls of NaSSa?
* Less sexual dysfunction * Weight gain/sedation are worse at lower dose (7.5-15 mg)
48
What are the mechanism of action of Serotonin modulator?
* Serotonin reuptake inhibitor, 5-HT1A partial agonist * Similar to SSRI and buspirone
49
What are the clinical pearls of serotonin modulator?
* Dose adjust with CYP3A4 inhibitor * Must take with food to increase bioavailability * Lowest incidence of sexual dysfunction
50
What is the mechanism of action of tricylic antidepressant?
* Presynaptic inhibition of norepinephrine and serotonin reuptake--> increase NE and 5-HT in the synaptic cleft * Varying affinities for H1, alpha adrenergic, and muscarinic antagonist
51
What are the common adverse effects of tricyclic antidepressants?
* Anticholinergic * Antihistaminergic * Orthostasis * Photosensitivity
52
What are the serious adverse events of tricyclic antidepressants?
* Cardiotoxicity (QTc prolongation and risk of MI) * Decreased seizure threshold
53
What are the clinical pearls of amitriptyline?
* Most cholinergic and alphalytic * More often used for chronic pain and migraine
54
What are the clinical pearls of clompramine?
* Most serotonergic * FDA approved for OCD
55
What are the clinical pearls of desipramine?
* Most noradrenergic * Low anticholinergic properties
56
What are the clinical pearls of doxepin?
Most antihistamine
57
What are the clinical pearls of imipramine?
* Used for GAD * Best for panic disorder with agoraphobia
58
What are the clinical pearls of nortriptyline?
* Low anticholinergic properties * Best tolerated TCA
59
What is the mechanism of action of Monoamine Oxidase Inhibitor (MAO-Is)?
Inhibition of monoamine oxidase enzymes (MAO-A & MAO-B) resulting in increased concentrations of norepinephrine, serotonin & dopamine in synapse
60
What are the adverse effects of MAOIs?
Common: * Hypotension * Dizziness * Urinary retention, constipation, and xerostomia Serious: * Hypertensive crisis--> drug-food interactions * Serotonin syndrome--> drug-drug interaction
61
Hypertensive Crisis
Diastolic blood pressure > 120 mm Hg
62
What are some presentations of Hypertensive crisis?
* Occipital headache * Palpitations * Neck stiffnes/soreness * Nausea and/or vomiting * Dilated pupils, photophobia * Tachycardia or bradycardia * Chest pain
63
What is the dietary modifications of hypertensive crisis?
Avoid tyramine
64
How do you treat hypertensive crisis?
Phentolamine (also nifedipine and chlorpromazine)
65
Which antidepressants should you avoid if you have hypertensive crisis?
* TCAs * NRIs * SNRIs * NDRIs
66
What are some clinical pearls of Phenelzine?
* Increased weight gain * May cause hepatoxicity (rare)
67
What are some clinical pearls of selegiline?
* Low doses selective for MAO-B (increases dopamine) * No need for dietary restriction with 6 mg/24hr patch * Drug-drug interactions are still a concern
68
What are some clinical pearls of Tranylcypromine?
* Structurally similar to amphetamine--> stimulating * Can cause insomnia * Transient hypertension
69
What is the Hunter's Criteria of Serotonin Syndrome?
* Spontaneous clonus * Inducible clonus + agitation or diaphoresis * Ocular clonus + agitation or diaphoresis * Tremor + hyperreflexia * Hypertonia + temperature > 35 C + ocular clonus or inducible clonus
70
What are some drug interactions of antidepressants for Serotonin Syndrome?
* SSRIs * TCAs * SNRIs * Mirtazapine * MAO-Is
71
What is the drug interaction of Antibiotics for Serotonin Syndrome?
Linezolid
72
What are some drug interactions of appetite suppressants for Serotonin Syndrome?
Sibutramine
73
What are some drug interactions of opioids for Serotonin Syndrome?
* Dextromethorphan * Meperidine * Methadone * Tramadol * Fentanyl
74
What are the washout periods to prevent Serotonin Syndrome with MAOIs?
MAO-I--> non-MAO-I antidepressant * Allow for 2-week washout period Non-MAO-I antidepressant--> MAO-I * Allow for 2-week washout period * Allow for 5-week washout period after fluoxetine MAO-I--> MAO-I * Allow for 2-week washout period
75
What is the boxed warning on ALL antidepressants?
* Seen in children/adolescents up to 24 years old * Notify family/caregiver to monitor * Balance benefits vs risk
76
What is the symptoms of Discontinuation Syndrome?
* Flu-like, paresthesia * Most severe: venlfaxine > SSRIs
77
What is the onset and duration of Discontinuation Syndrome?
* Onset: 1-2 days after discontinuation * Duration: 1-2 weeks depending on medication half-life
78
What medication do you avoid in pregnant patients?
Paroxetine
79
What is the empiric therapy selection based on?
* History of antidepressant response * Family history of antidepressant response * Concurrent with diseaes states and drug therapy * Drug interactions * Adverse effect profile * Cost

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