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CNS: MDD > Wilkening's > Flashcards

Wilkening's Flashcards

1
Q

What is MDD?

A

MDD is a serious and sometimes life-threatening illness

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2
Q

DSM- 5 Diagnostic Criteria

A
  • episode must cause significant dysfunction or distress
  • must not be due to a substance or general medical condition
  • last almost all day nearly every day for a minimum of 2 weeks
  • have a least 5 of the following symptoms
    depressed mood (is a must)
    sleep
    interest (is a must)
    guilt
    energy (decreased)
    concentration (impaired)
    appetite (usually decreased)
    psychomotor (slow movement)
    suicide (thoughts or suicide)
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3
Q

What does MDD impact?

A

core domains impacted by MDD include: mood, cognition and physical symptoms

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4
Q

MDD Specifiers

A 
Anxious Distress (most common)
Melancholic Features (most common)
Atypical presentation
Psychotic features
Seasonal pattern
Peripartum onset
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5
Q

Anxious distress

A

defined as the presence of at least 2 of the following during the majority of days of a MDD episode

  1. feeling keyed up or tense
  2. feeling unusually restless
  3. difficulty concentrating because of worry
  4. fear that something awful may happen
  5. feeling that the individual might lose control of him/herself
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6
Q

Melancholic features

A
  1. loss of pleasure in all, or almost all activities
  2. lack of reactivity to usually pleasurable stimuli
    * *intense sad feelings
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7
Q

Atypical presentation

A

instead of someone losing weight they are gaining weight, opposite of the “norm”

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8
Q

Seasonal pattern

A

a regular temporal relationship between the onset of MDD episodes and a particular time of year

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9
Q

Peripartum onset

A

current MDD episode of mood symptoms occurs during pregnancy or in the 4 weeks following delivery

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10
Q

Adverse Health Behaviors

A
  • smoking: may be form of self-medication. as depressive symptom severity increases, the probability of smoking cessation decreases
  • alcohol use: depressant
  • sedentary lifestyle: modifiable risk factor
  • sleep disturbance: poor sleep throughout lifespan
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11
Q

MAOIs: General Considerations

A

MOA: increases concentrations of monoamines by IRREVERSIBLE inhibition of the enzyme (monoamine oxidase) that’s responsible for their breakdown
MAO-A: 5-HT & NE
MAO-B: DA
Duration: activity= time to create new MAO enzymes (2-3 weeks)
***after stopping treatment with an interacting med, 4-5 t 1/2 of the drug should elapse PRIOR to initiation

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12
Q

MAOIs: Switching antidepressants

A
  1. antidepressant treatment–> treatment failure–> 5 t 1/2 of the drug–> initiate MAOI
  2. MAOI treatment–> treatment failure/intolerance–> 2-3 week washout–> initiate new antidepressant
  3. Fluoxetine (Prozac) treatment–> treatment failure–> 5 week washout–> initiate MAOI
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13
Q

Isocarboxazid (Marplan)

A

Non-selective

Caution: doses > 40 mg/day

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14
Q

Phenelzine (Nardil)

A

Non-selective

Hepatotoxic (rarely)

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15
Q

Tranylcypromine (Parnate)

A

Non-selective

Give last dose early in the day

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16
Q

Selegiline (Emsam, Eldepryl, Zelapar)

A

Selective for MAO-B @ low doses, Non-selective @ high doses

Only parenteral antidepressant on market

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17
Q

MAOIs: Adverse effect profile

A

Potential: hypotension/syncope, dry mouth, headache, GI discomfort/upset, sexual dysfunction, constipation (selegiline= diarrhea), weight gain (selegiline= weight loss), & edema
Serious: Hypertensive crisis (over stimulation of noradrenergic system)

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18
Q

MAOIs: DDI’s

A 
other serotonergic agents (5-HT): most antidepressants, dextromethorphan, some opiods (fentanyl, methsdone, tramadol), chlorpheniramine and brompheniramine
sympathomimetic agents (NE): pseudoephedrine, cocaine, amphetamine, oxymetazoline, NE reuptake inhibitors
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19
Q

MAOIs: Contraindications

A

Pheochromocytoma (adrenal tumor)
concurrent sympathomimetic or serotonergic agents
tyramine-containing foods
surgery (d/c at least 10 days prior b/c of anesthesia)

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20
Q

MAOIs: Warnings

A 
Bipolar disorder (manic state)
Hyperthyroidism (hypertensive crisis)
CV disease (increase HR & orthostatic hypotension)
***6 mg of selegiline doesn't require a diet restriction
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21
Q

TCAs: General Considerations

A

MOA: prevent reuptake of presynaptic NE and 5-HT by inhibiting their transporters, individual TCAs have varying affinity for other receptors
NTI meds: PK parameters can make potentially fatal in overdose
- highly lipophillic compounds with large volumes of distribution
- highly protein bound (not easily removed by hemodialysis or hemofiltration)
- cardiac arrhythmias typical cause of death in OD situation

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22
Q

Secondary Amine TCA’s: better @ increasing NE concentrations

A

Amoxapine (Asendin): metabolite of loxapine–> antipsychotic properties
Desipramine (Norpramin)
Nortriptyline (Pamelor): better choice for geriatrics
Protriptyline (Vivactil)

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23
Q

Tertiary Amine TCA’s: better @ increaseinf 5-HT concentrations

A

Amitriptyline (Elavil): migraine prophylaxis, post-herpetic neuralgia
Doxepin (Silenor/Sinequan): FDA- insomnia treatment
Clomipramine (Anafranil): FDA- OCD tx
Imipramine (Tofranil/Tofranil-PM): active metabolite (despiramine)

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24
Q

TCAs: Adverse effect profile

A

sedation, weight gain
anticholinergic effects (blurred vision, urinary retention, dry mouth, constipation, cognitive impairment/delirium)
CV effects (QTc prolongation, orthostatic hypotension, arrhythmias, sexual dysfunction)
tertiary > secondary for side effects

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25
Q

TCAs: Warnings & Clinical Considerations

A

Discontinuation syndrome
overdose/toxicity (significant hypotension, confusion, arrhythmias, seizures, coma)
reduced seizure threshold
bipolar disorder –> manic switch
geriatric patients –> anti-cholinergic effects
concomitant use with MAOIs –> serotonin syndrome or hypertensive crisis

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26
Q

SSRIs: General Considerations

A 
MOA: selectively inhibits presynaptic reuptake of 5-HT by inhibiting the transporter
Class considerations: most commonly used class of antidepressants (more favorable adverse effect profile), not fatal in OD compared to other antidepressant classes (don't block Na+ channels like TCAs, no effect on NE or muscarinic/histaminic receptors), can be activating, best administered in the morning (except paroxetine)
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27
Q

Citalopram (Celexa)

A

QTc prolongation

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28
Q

Escitalopram (Lexapro)

A

S-enantiomer of citalopram (fewer SE)

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29
Q

Fluoxetine (Prozac)

A

longest t 1/2 (1-9 days); active metabolite t 1/2 ~ 16 days

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30
Q

Paroxetine (Paxil)

A

weight gain significant

**discontinuation syndrome

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31
Q

Sertraline (Zoloft)

A

well tolerated; studied in CHD

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32
Q

SSRIs: DDI’s

A
  • alcohol
  • anticoagulants, antiplatelet medications & NSAIDs
  • CYP 2D6 substrates (fluoxetine and paroxetine are potent inhibitors
  • methadone (QTc prolongation)
  • other serotonergic agents (serotonin syndrome)
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33
Q

SSRIs: Adverse effect profile

A

sexual dysfunction
nausea & GI discomfort (@ high doses)
anxiety (@ high doses)
weight gain (especially paroxetine)
insomnia (except paroxetine)
increased risk for GI bleed (serotonin receptors & platelet activation)
SIADH (syndrome of inappropriate anti-diuretic hormone, elderly and ppl on thiazide diuretics)

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34
Q

SSRIs: Warnings & Contraindications

A 
associated with increased fracture rate and decreased bone mineral density
use of citalopram with other agents that sig. prolong QTc
concomitant MAOI (serotonin syndrome)
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35
Q

SNRIs: General Considerations

A

MOA: inhibits presynaptic reuptake of 5-HT and nE by inhibition of transporters
Class considerations: generally well tolerated, good for patients with co-morbid pain disorders, cymbalta contains delayed-released beads and should not be opened or chewed (not recommended for patients with sig. alcohol use)
***diminished hepatic function: alcohol use, hepatitis, people who use IV drugs

36
Q

Desvenlafaxine (Pristiq)

A

do not crush, divide, or chew

active metabolite of venlafaxine

37
Q

Venlafaxine (Effexor)

A

can cause HTN (doses > 300 mg)
SSRI-like until dose > 225 mg
***discontinuation syndrome

38
Q

Duloxetine (Cymbalta)

A

other FDA approvals: fibromyalgia, diabetic neuropathy & GAD, hepatotoxicity
***3rd worse discontinuation syndrome

39
Q

Levomilnacipran (Fetzima)

A

new agent

ADR: nausea

40
Q

Milnacipran (Savella)

A

NOT for MDD
FDA: fibromyalgia
ADR: nausea 37%

41
Q

SNRIs: DDI’s

A

***alcohol
anticoagulants, antiplatelet medications, NSAIDs
MAOIs (serotonin syndrome & hypertensive crisis)
other serotonergic agents

42
Q

SNRIs: Adverse effect profile

A 
GI upset (most common): nausea, vomiting
sexual dysfunction (except milnacipran)
agitation/activation: insomnia b/c of NE
cardiovascular: HTN, tachycardia/palpitations b/c of NE
headache
43
Q

SNRIs: Warnings & Contraindications

A 
hepatotoxicity
bipolar disorder (manic switch)
GI bleed risk
serotonin syndrome
discontinuation syndrome (paroxetine & venlafaxine)
increases in blood pressure
concomitant MAOIs
44
Q

NDRI: General Considerations

A

MOA: increases DA & NE concentrations by inhibiting presynaptic reuptake
Considerations: activating (can cause insomnia, and worsen anxiety), not associated with sexual dysfunction or weight gain

45
Q

Bupropion IR (Wellbutrin)

A

dosed TID or QID

46
Q

Bupropion SR (Zyban/ Wellbutrin SR)

A

FDA approved for smoking cessation

47
Q

Bupropion XL (Wellbutrin XL)

A

do not crush or chew. swallow whole

48
Q

NDRI: Adverse effect profile

A

potential: GI (nausea, vomiting, GI upset), agitation/activation, headache, insomnia
serious: seizure (lowers seizure threshold)

49
Q

NDRI: Warnings & Contraindications

A

can lower seizure threshold
concomitant MAOIs (hypertensive crisis)
potent 2D6 inhibitor (antipsycotics)
Contraindicated: eating disorders (b/c of electrolyte imbalances which is a risk for seizures) & seizure disorders

50
Q

NDRI: Boxed Warning

A

neuropsychiatric events have occured in patients taking bupropion for smoking cessation

51
Q

Atypical Antidepressants: Trazodone (Desyrel), Nefazodone (Serzone), & Vilazodone (Viibryd)

A

MOA (traz & nefaz): weak inhibition of 5-HT and NE reuptake, weak alpha-1 antagonists, weak 5-HT2 antagonist, Histamine antagonists (trazodone)
Class considerations: trazodone, often used for sleep
sleep dose: 25-200 mg at bedtime
depression dose: 150-600 mg/day in divided doses
***histaminergic effects–> sleep & weight gain

52
Q

Nefazodone (Serzone)

A

BBW: hepatotoxicity
ADR: anticholinergic (sedation, orthostatic hypotension)

53
Q

Trazodone (Desyrel)

A

often used for sleep

ADR: very sedating! orthostatic hypotension, QTc prolongation, priapism

54
Q

Vilazodone (Viibryd)

A

MOA: inhibits serotonin reuptake and also 5-HT1A partial agonist
activating
ADR: insomnia, N/V and diarrhea

55
Q

Mirtazapine (Remeron)

A

MOA: presynaptic alpha-2 antagonist –> increases NE and 5-HT concentrations
Considerations: anticholinergic and antihistaminic properties (sig. drowsiness & weight gain)
**theoretical: adverse effects are more prominent with lower doses

56
Q

Vortioxetine (Trintellix/Brintellix)

A

MOA: SSRI-like activity, along with activity at multitude of 5-HT receptors
may have unique role in improving cognition
likely to be very expensive

57
Q

Alternative supplements for depression

A

St. John’s Wort (hypericum perforatum)
herbal dietary supplement available OTC; 300 mg TID for mild-mod depression
MOA: non-selective MAOI (weak), inhibits 5-HT, NE and DA transport
induces CYP1A2, 2C9, 2C19, 2D6 & 3A4
alters PGP activity

58
Q

Antidepressant Selection

A

Empiric selection of antidepressant therapy

  • past history of antidepressant response
  • family history of antidepressant response
  • features of depression (anxious features, insomnia, psychomotor retardation, etc)
  • concurrent disease states and drug therapy (pain, neuropathies, hypertension, h/o seizures, seizure DO)
  • drug interactions (paroxetine, fluoxetine)
  • adverse effect profile (weight gain, sexual side effects, n/v/d)
  • suicide risk
  • cost
59
Q

Other Somatic Therapies

A
  1. electroconvulsive therapy (ECT): “shock treatments” –> very effective, particularly for patients with refractory or severe illness
  2. transcranial magnestic stimulation (TMS): FDA approved for treatment-resistant MDD
60
Q

Treatment Guidelines

A
  1. the world federation of societies of biological psychiatry (WFSBP)
  2. the american psychiatric association (APA)
  3. national institute of health and clinical excellence (NICE)
  4. VA/DoD. clinical practice guideline for management of MDD
61
Q

Deciding to Treat

A
  • prevalence of non-adherence reported to be 29-42% at 4 weeks
  • -> increases to 63-76%
  • non-adherence/suboptimal duration of treatment increases rates of recurrence and chronicity of illness
  • overcoming barriers to treatment
  • -> identifying factors which can contribute to non-adherence (adverse effects, stigma, cost)
62
Q

Terminology: HAM-D, Remission & Response

A

HAM-D 17: scale administered by professional to rate severity of depression; used as standard in clinical trials. score of 0-7= standard (high score = more severe depression)
Remission: HAM-D score = 7 (essentially, ABSENCE of symptoms)
Response: reduction of HAM-D by >/= 50% in total score (essentially, REDUCTION in symptoms)

63
Q

APA: Phases & Goals of Treatment

A
  • Acute phase: induce remission, return to baseline level of functioning
  • Continuation phase: continue same medication and dose for 6-12 months for pts successfully treated in acute phase, prevent recurrence of subsequent depressive episode
  • Maintenance phase: reduce risk of recurrence, indicated for those with >/= 3 MDD episodes in lifetime
64
Q

DSM-5 Criteria: MDD Severity

A

***will be defined for us on the exam!
defined in DSM-5, also use assessment called PHQ-9 (self-administered assessment)
-mild: few symptoms in excess of those needed for diagnosis
-moderate: number of symptoms, intensity of symptoms
-severe: number of symptoms substantially in excess of what is required for diagnosis

65
Q

APA: Recommendations

A

***Know this!!!
1st line mild/mod: psycotherapy +/- pharmacotherapy (SSRI, SNRI, mirtazapine, bupropion)
1st line mod/severe: psycotherapy + pharmacotherapy OR pharmacotherapy OR ECT

66
Q

APA: Adequate Treatment Trial

A

allow up to 4-8 weeks of antidepressant treatment to determine responsiveness

67
Q

Antidepressants: Lag in Therapeutic Effect

A

Neurotransmitter Receptor Hypothesis

  • dysregulation of receptors
  • adaptive down-regulation and desensitization of receptors over time
68
Q

When Should We Reassess Response?

A

“adequate trial” –> maximized dose for 4-8 weeks

however, early improvement may predict response > 20% reduction on the HAM-D at 2 weeks

69
Q

Timeline of Symptom Improvement

A

2 weeks: increased activity, sex drive, self care, concentration, memory
4-8 weeks: improved depressed mood, decreases/remitted feelings of hopelessness
***response= decrease in symptoms, physical symptoms get better 1st!!

70
Q

Recurrence of MDD Episode

A

patients who discontinue antidepressants prior to 1 tear are 2x’s as likely to relapse within 1 year and each recurrent episode may potentially lower threshold for depression
1st episode: 50%
2nd epsiode: 70%
3rd + episode: > 90%

71
Q

Duration of Therapy

A

1 MDD episode: >/= 6 months of full remission before considering taper
2 MDD episodes: >/= 1 year full remission before taper
3 or more episodes: indefinite treatment

72
Q

Patient Failed 1st line Treatment

A

Very common (1st agent usually effective < 50% of time)
related issues: increased MDD severity, psychotic symptoms, suicidal ideation
***can be related to POOR ADHERENCE or ADVERSE EFFECTS

73
Q

Failed 1st-line: Next Steps

A
  • change treatment if moderate improvement is not observed with initial antidepressant:
    maximize dosing
    change to another agent within the same class (SSRI to another SSRI)
    change to an agent in another class (SSRI to SNRI)
74
Q

Partial Response: Augmentation Strategies

A
  1. add 2nd antidepressant with different MAO, OR mirtazapine, bupropion
  2. add SGA (2nd gen antipsycotic), very common augmentation strategy in practice, quetiapine, aripiprazole, olanzapine (+ fluoxetine)
  3. add lithium, OR decrease suicidality in patients with MDD and BD, average dose in STAR*D= 860 mg, level 0.6 mEq/L
  4. add T3 or buspirone
    * **only if a person has partial response after 4-8 weeks
75
Q

Augmentation Strategies flow chart: Partial response

A

No response: antidepressant initiated
1-4 weeks: partial response (assess adherence, increase dose, if appropriate)
4-8 weeks: increase dose OR supplement with augmentation med

76
Q

Augmentation Strategies flow chart: No response

A 
No response: antidepressant initiated
1-4 weeks: assess adherence and optimize dose
4-8 weeks: change meds (either in same class or to alternate class) OR consider ECT
77
Q

Augmentation Strategies flow chart: Full response

A

No response: antidepressant initiated
1-4 weeks: continue if no problems with tolerability
4-8 weeks: continuation phase

78
Q

Antidepressant Discontinuation Syndrome

A

patients should be tapered off of antidepressants AT LEAST over a few weeks to prevent d/c symptoms
- it is important to educate patients that they SHOULD NOT ABRUPTLY QUIT TAKING THESE MEDICATIONS, as d/c symptoms can include:
insomnia, irritability, anxiety, vivid dreams, flu-like symptoms, return of depression symptoms
all meds can do this but worse with paroxetine & venlafaxine, can use fluoxetine b/c of long t 1/2
****advise pts NOT to double doses if they forget a dose

79
Q

Serotonin Syndrome

A

Definition: potentially life-threatening condition brought on by increased serotonergic activity in the CNS
Potential causes: DDI’s, intentional/unintentional OD, history is IMPERATIVE to make diagnosis
**you have to rule out other causes before claiming a pt has this, you can also not draw out a 5-HT serum

80
Q

Serotonin Syndrome Symtpoms

A

Sx, may include 3 or more:
autonomic instability, irritability/agitation, diaphoresis (sweat), fever, hyperthermia, hyperreflexia, increased bowel sounds, mental status changes, myoclonus (twitches/jerks)

81
Q

Serotonin Syndrome treatment

A
  • discontinue serotonergic agents
  • supportive care
  • cyproheptadine??
82
Q

Antidepressant Boxed Warning

A

found on ALL antidepressant labeling
in short-term studies, antidepressants increased risk of suicidal behavior and thinking in children, adolescents, and adults < 24 yo

83
Q

Depression & Pregnancy

A

frequent SSRI utilization (except paroxetine: category X)
risks: persistent pulmonary hypertension of the newborn, antidepressant discontinuation syndrome, Austism spectrum disorder
risk vs. benefit: untreated depression (low birth weight, fetal growth restriction, prematurity, postnatal complications)
appropriate resources: american college of obstetrics & gynocology or briggs: drugs in pregnancy and lactation
***ECT in severely depressed women

84
Q

Suicidality

A
  • most serious consequences of MDD
  • spectrum
  • there were 41,149 deaths by suicide in 2013, 3rd leading cause of death for ppl aged 18-24
  • can impact antidepressant selection
  • demographics: women attempt suicide more, but men are more likely to complete act. caucasian males > 85 yo have the HIGHEST RATE of completed suicide
85
Q

Suicide Risk & Approach to Triage

A
  • language
  • levels of risk
  • YOU have a responsibilty to appropriately connect patients to services
  • pharmacist resources: local ER, national suicide hotline, www.suicidology.org, san antonio specific (crisis care center)
86
Q

Risk Factors for MDD

A
  • 1st-degree relatives (2-4 fold increased risk)
  • some comorbid medical illness (DM, chronic pain, HIV, cancer, post-MI)
  • previous depressive episode (50-85% will have a recurrent episode)
  • certain medications and drugs (interferon, reserpine, alcohol, illicit drugs like cocaine, meth)
  • traumatic childhood experiences
  • female sex
87
Q

Epidemiology

A
  • around 350 million people worldwide affected
  • more prevalent in: females (2:1 to males), people aged 40-59 yo, individuals below the poverty line
  • the % of americans on antidpressants doubled from 1999-2012 (6.8-13%)
  • roughly 1 in 10 americans >/= 12 years takes an antidepressant
  • 35.5% of persons with severe depressive symptoms reported seeking mental health care in the past year
  • 20% of persons with moderate depressive symptoms reported seeking mental health care in the past year

CNS: MDD (2 decks)

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