Antidepressants and Depression Flashcards by Alexander Nachlis

epidemiology

5% adults with depression

leading cause of disability worldwide

US lifetime prevalence 20%

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risk factors

2:1 F:M
native
1st deg relative

middle aged, stress, recent loss

chronic medical illness

personal hx of MDD and/or SUD

previous major depressive episodes

risk inc with number of episodes

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Pathophysiology of MDD Neuroanatomical abnormalities

Multiple structures

overactive amygdala

overactive subgenual anterior cingulated cortex

decreased dorsolateral PFC activity

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Pathophysiology of MDD Neurotransmitter involvement

Monoamine hypothesis
o 1950s development with noted dec of 5HT, NE, DA and noted MAOI and TPA improvement but missed delayed onset effect on mood and its relation to synaptic changes

Dysregulation hypothesis
o Accounts for delay in onset of antidepressant action and shows more than inc or dec in concentration

Chronic stress model
o Effect on hypothalamic (HPA) leads to secretion of glucocorticoid and cortisol which leads to neurogenesis in the hippocampus

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DSM MDD

1 or more major depressive episodes with no hx of manic or mixed mood episodes
AND
5 or more of sx nearly every day for at least 2 wks

Depressed mood most of the time and on most days

Decreased interest or pleasure in daily activities most of the time and on most days

Significant changes in weight or appetite

Significant changes in sleep

Psychomotor agitation or retardation which is observable by others

Fatigue or decreased energy

Feelings of worthlessness or inappropriate guilt

Decreased concentration or difficulty making decisions

Recurrent thoughts of death, suicidal ideation without a specific plan, specific plan for committing suicide, or a suicide attempt

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Clinical status

severity, psychotic features?

severity
- mild: 5 or 6 sx and minimal functional impairment
-severe: nearly all sx and significant impairment of functioning

can be present with psychotic features

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clinical status

remission, chronic definition

remission: absence of significant sx for at least 2 months

chronic MDD: full criteria for major depressive episode for a minimum of 2 years

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descriptive specifiers for MDD

Anxious distress
* Inc SI and worse outcome
* Tension, fear restless

Mixed features
* Mania but not criteria for specific but is RF for BP

Catatonic features
* Immobility etc

Melancholic features
* Severe depression
* Lack of stimuli

Atypical features
* Mood reactivity issue
* Weight, sleep

Peripartum onset
* During or after

Seasonal pattern

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treatment by generation/class

1st gen
- TCA
-MAOI

2nd gen
-SSRI
-SNRI
-Buproprion
-Mirtazapine
- Trazodone

Newer
-Vilazodone
-Vortioxetine

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SSRI MOA

inhibit presynaptic serotonin reuptake by interfering with 5HT transporter

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SSRI side effects

Headache
wt gain
GI
sex
agitation/anxiety (when starting)

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SSRI rx and initial dosing

Citalopram (Celexa ®): initial dose 20 mg PO once daily
- note QT prolong is dose dependent

Escitalopram (Lexapro ®): initial dose 10 mg PO once daily

Sertraline (Zoloft ®): initial dose 25-50 mg PO once daily
- QT

Paroxetine (Paxil ®): initial dose 20 mg PO once daily
- short half life
- higher risk discontinuation syndrome

Fluoxetine (Prozac ®)* : initial dose 20 mg PO once daily
- long half life
- QT

Fluvoxamine (Luvox ®) : initial 50 mg PO once daily

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SNRI MOA

5HT receptors too BUT also inhibit NE reuptake (both by inhibition of transporters)

That leads to inc in 5HT and NE in the cleft

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SNRI side effects

Same as SSRI
AND

hypertension
++ nausea/diarrhea
sweating
dry mouth
dizziness
fatigue

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SNRI rx and initial dose

Duloxetine (Cymbalta ®): initial dose 40-60 mg PO once daily
- pain
-inhibits NE more than venlafaxine but that causes more dry mouth and constipation

Venlafaxine (Effexor ®): initial dose 37.5-75 mg PO once daily
- pain
- may inc cholestrol

Desvenlafaxine (Pristiq ®): initial dose 50 mg PO once daily

Levomilnacipran (Fetzima ®): initial dose 20 mg PO once daily
-recent approval

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TCA MOA

Inhibit presynaptic 5HT and NE reuptake by inhibition of transporters which leads to inc in 5HT and NE in cleft

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TCA AE

o Tertiary amine
More sedation and anticholinergic AE
5HT

o Secondary amine
More CV effect
Better tolerated
NE

overdose potential and cardiac effects

anticholinergic AE: confusion, constipation, wt gain, sedation

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Tertiary amines (5HT) rx and initial dose

Amitriptyline (Elavil ®): initial dose 25-50 mg PO once daily

Imipramine (Tofranil ®): initial dose 25-50 mg PO once daily

Clomipramine (Anafranil ®): initial dose 25-50 mg PO once daily

Doxepin (Silenor ®): initial dose 25-50 mg PO once daily

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Secondary amines (NE) rx and initial dose

Nortriptyline (Pamelor ®): initial dose 25 mg PO once daily

Desipramine (Norpramin ®): initial dose 25-50 mg PO once daily

Amoxapine (Asendin®): initial dose 25-50 mg PO 1-3 times daily

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MAOI MOA

Irreversibly inhibit monoamine oxidase preventing metabolism of NE, 5HT, and dopamine

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MAOI 2 types

MAO-A
MAO-B

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MAOI drug interactions

amphetamines

carbamazepine

decongestants

ephedrine

dextromethorphan

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MAOI AE

Cardiovascular side effects
–require dietary restrictions (aged meat/cheese, soy, or tyramine containing foods)
–Hypertensive crisis

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MAOI rx and initial dose

Tranylcypromine (Parnate ®): initial dose 10-30 mg PO in divided doses

Phenelzine (Nardil ®): initial dose 15 mg PO 1-3 times daily

Isocarboxazid (Marplan ®): initial dose 10 mg PO twice daily

Selegiline transdermal (Emsam ®): initial dose 6 mg/24-hour patch once daily

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Bupropion MOA

Inhibits DA and NE transporters, increasing dopamine and norepinephrine concentrations in the synapse

Bupropion initial dose

IR 100 mg PO twice daily 12-hour ER 150 mg PO once daily 24-hour ER 150 mg PO once daily

Bupropion AE

Insomnia (11-40%) Activation/anxiety (2-30%) Seizure (0.1% at approved doses), may be no higher than other antidepressants and close to incidence in general population. --Highly dose related at > 600mg (2%) --Consider risk of seizures in populations with substance use disorder, and history of head trauma Hypertension (2.5-4.3%) Less sexual dysfunction and weight gain

Mirtazapine (remeron) MOA

increases synaptic concentration of serotonin and norepinephrine through presynaptic alpha 2 antagonism Also, a 5HT2 and 5HT3 antagonist and histamine-1 antagonist

Mirtazapine (remeron) initial dose

15mg PO qd

Mirtazapine (remeron) AE

Sedation (advise patient to take at bedtime) Increased appetite --may lead to weight gain Hypertriglyceridemia Liver toxicity and agranulocytosis (rare)

Trazodone and Nefazodone MOA

weak inhibition of presynaptic serotonin and norepinephrine reuptake (for nefazodone), 5HT2a antagonist, weak alpha-1 antagonist, and histamine-1 antagonist (trazodone > nefazodone)

Trazodone and Nefazodone initial dose

Trazodone: IR 50 mg PO twice daily or ER 150 mg PO once daily Nefazodone: 100 mg PO twice daily

Trazodone and Nefazodone AE

Nefazodone -Nausea (32%), headache (26%), dry mouth (25%) -Hepatic failure (routine liver function test monitoring required) Trazodone -Somnolence, nausea (21%), dry mouth (14-33%), and dizziness (25%)

Vortioxetine (trintellix) MOA

Inhibition of 5HT reuptake Serotonin 5HT3, 5HT1D, 5HT7 antagonism Serotonin 5HT1a agonist

Vortioxetine (trintellix) initial dose

5-10mg PO qd

Vortioxetine (trintellix) AE

GI Dry mouth Sex dysfunction

Vilazodone (viibryd) MOA

inhibition of presynaptic 5-HT reuptake by inhibition of the 5-HT transporter --leads to increased 5-HT in synaptic cleft Also, a 5-HT1a partial agonist May have some affinity for NE and DA transporters

Vilazodone (viibryd) initial dose

10mg PO qd

Vilazodone (viibryd) AE

GI insomnia

MDD pos and neg for sedation

pos - paroxetine -mirtazapine - trazodone neg -Buproprion -fluoxetine -sertraline

MDD pos and neg for weight gain

pos - paroxetine -mirtazapine neg -Buproprion -Duloxetine -fluoxetine

MDD pos and neg for bleeding risk

pos -SSRI neg -Bupropion -mirtazapine

MDD pos and neg for sex dysfunction

pos - paroxetine -venlafaxine -sertraline neg -Buproprion -mirtazapine -vortioxetine

MDD pos and neg for hypertension

pos -bupropion -venlafaxine neg -SSRI

discontinuation syndrome

Flu like symptoms that occur after abrupt discontinuation of SSRI/SNRI, taper slow (except fluoxetine)

Star-D for depression

1. Citalopram 2. Switch - Sertraline - Bupropion -Venlafaxine -CBT 2. Augment -Bupropion -Buspirone -CBT 2a - venlafaxine -Bupropion 3. Switch -mirtazapine -nortyptiline 3. Augment - Lithium -Thyroid hormone -largest and longest study -compared acute and long term tx outcomes associated with steps cumulative remission rate: 67%

APA 1st line and 2nd line

mild-mod -psychotherapy +/- SSRI, SNRI, mirtaz, or bupro mod-severe - pharmacotherapy +/- psychotherapy Psychotic features - antidepressant + Antipsychotic - ECT- severe depression 2nd - switch but keep mono - augment with antidepressant with diff mechanism - quetapine -psychotherapy

NICE guideline 1st

mild -psychotherapy mod-sev -psych +/- pharma severe -ECT

CANMAT 1st line

1st -SSRI, SNRI, and other newer agents based on safety and tolerability over TCAs or MAOIs Psychotic features -Antidepressant + Antipsychotic

CANMAT 1st line adjunctive

1st -Aripiprazole, quetiapine, risperidone

Approach to tx of MDD 1-4 wks

Response - full- maintain tx -partial/none--assess adherence, inc as tolerated if 50% reduction in sx cont at optimal dose and monitor at 6, 8, 12 wks

Approach to tx of MDD 4-8 wks

Response - full- maintain tx -partial/none--inc as tolerated, switch if no response at 8 wks, augment

MDD dx improvement: sleep

trazodone mirtazapine paroxetine

MDD dx improvement: concentration

bupropion duloxetine fluoxetine

MDD dx improvement: anxiety

sertraline fluvoxamine paroxetine SNRI

MDD dx improvement: pain

SNRI

Rx choice based on

Past response (or family member response) to medication Other psychiatric co-morbidities Potential for drug interactions Safety Patient preference Cost

patient education- counseling

When to start working What to expect Adverse side effects Discontinuation syndrome

patient education- duration of therapy

1st episode – at least 6 months 2nd episode – at least 1 year 3rd episode – lifetime

new rx- Esketamine (spravato)

* Adjunct PO * Black box noted * For tx resistant * REMS * Expensive

new rx- brexanolone (zulresso)

* GABA- A * Postpartum * Infusion in facility * Black box * REMS * Very expensive

Antidepressants and Depression Flashcards

(61 cards)