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Psychosocial Medicine > Lecture 3: Antidepressants and Mood Stabilizers > Flashcards

Lecture 3: Antidepressants and Mood Stabilizers Flashcards

1
Q

Classes of Antidepressants (8)

A
  1. selective serotonin reuptake inhibitors (SSRIs)
  2. Serotonin norepinephrine reuptake inhibitors (SNRIs)
  3. Norepinephrine dopamines reuptake inhibitors (NDRI)
  4. Noradrenergic and Specific Serotonergic Antidepressants (NaSSa)
  5. Serotonin Antagaonist/Reuptake Inhibitors (SARIs/SPARI)
  6. Tricylclic Antidepressants (TCAs)
  7. Monoamine Oxidase Inhibitors (MOAIs)
  8. Misc.
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2
Q

Boxed warning

A

applies to any agent FDA=approved for depression (and some other)

  • increased risk of suicidality
    a. children, adolescents, young adults
    b. use cautiously with psycholotherapy if possible, frequent follow-ups
    c. suicide protective in patient > 65 years
    d. educate patients
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3
Q

Serotonin syndrome

3 signs and their symptoms

A

rapid onset, combo of 2+ serotonin agonists

  1. mental status change: agitation and pressured speech
  2. autonomic instability: tachycardia, diarrhea, shivering, diaphoresis, mydriasis
  3. Neuromuscular abnormalities: clonus, hyperflexia, tremor, seizure
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4
Q

Antidepressant Withdrawal

A
  1. agents should be tapered over weeks if able
    - EXCEP. fluoxetine self-tapers
  2. Abrupt discontinuation can precipitate a withdrawal syndrome
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5
Q

Withdrawal Syndrome (FINISH)

A 
Flu-like symptoms
Insomnia
Nauseau
Iritability
Sensory disturbance
Headache
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6
Q

SSRIs method of action

A

-inhibition of reuptake of serotonin (5-HT) in the presynaptic neuron of the central nervous system

  • 1st line tx of MDD
    a. well tolerated
    b. low rx toxicity in OD
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7
Q

SEE 12 if necessary.

A

slide 12

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8
Q

SSRIs adverse effects (11)

A
  1. nausea/vomiting/diarrhea
    - MOST Sertraline
  2. Insomnia
    - MOST fluoxetine
  3. Fatigue/Sedation
    - MOST Paroxetine
  4. Weight Gain
    - Peroxetine
  5. Diaphoresis-usual sweating
  6. Sexual Dysfunction
  7. Seizures
  8. Headache
  9. SIADH (syndrome of inappropriate anti-diuretic hormone secretion)
  10. anxiety/agitation during 1st few days-weeks of tx
  11. risk of bleeding
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9
Q

SSRI: adverse effect

QT interval prolongation

Drug name, allowable amounts

A

citalopram with most documented evidence of effect

  • do not give > 40 mg a day or 20mg if 60 years or older
  • may be more toxic in OD than other SSRIs
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10
Q

SSRI Adverse effect

Anticholnergic effects

A

paroxetine, recommend to avoid in elderly

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11
Q

SEE 16

A

slide 16

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12
Q

SNRI side effects

all SNRIS (10)

A
  1. nausea
  2. dizziness
  3. insomnia
  4. sedation
  5. constipation
  6. sexual dysfunction
  7. urinary retention
  8. SIADH
  9. narrow angle glaucoma
  10. dose related to increase in diastolic blood pressure (more common in venlafaxine/desvenlafaxine)
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13
Q

SSNRI adverse effects

Duloxetine (3)

A
  1. more anticholinergic effects
  2. urinary retention
  3. increases rx of hepatotoxicity esp. with ETOH
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14
Q

SSNRI adverse effects

Levomilnacipran

A

tachycardia

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15
Q

bupropion/Wellbutrin

method of action

dose

half life

A

SSNRI

1st line, augmenting agent

MOA: inhibits reuptake transporters of synaptic dopamine, norepinephrine- no serotonergic effects

dose: 150-450 mg daily

available in IR,SR,XL formulation

t1/2: 8-24 hours

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16
Q

Buproprion/wellbutrin

adverse effects
contraindication

A

SSNRI

AE: nausea, vomiting, weight loss, tremor, insomnia, xerostomia, hypertension, low rx sexual dysfunction

C: seizure disorder, high alcohol/benzodiazepine intake

  • abrupt d/c of sedative can increase rx of seizure
  • bullemia, anorexia nervosa
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17
Q

Mirtazapine/remeron

Method action

dose

A

SSNRI

1st line agent with compelling reason

MOA: antagonized presynaptic alpha-2 adrenergic receptors (increase NE, 5-HT) and protsynaptic 5-HT receptors

D: 15-60 mg daily

  • 7.5 mg for insomnia
  • doses 15 mg and above typically acitvating
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18
Q

Vortioxetine/ Trintellix

MOA

Dosage

Adverse effects

A

SSNRI

MOA: SSRI with 5-HT 1A agonism, mixed antagonist/partial agonist

Dose: 10 mg daily, max dose 20 mg daily

AE: nausea, constipation, vomiting, sexual dysfunction

*wait 21 days before starting MAOI (lone t1/2)

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19
Q

Nefazodone (Serzone)/Trazodone (desire)

MOA
Dose
Adverser effects

A

SSNRI

3rd line augmenting (d/t sedation)

MOA: antagonist at postsynaptic 5HT2, inhibits reuptake of serotonins

Dose: trazodone: 150-375 mg daily, 3 divided doses, XR form also available

nefazodone: 200-600 mg in 2 divided doses

AE: sedation, dizziness, orthostatic hypotension

trazodone-priapism (rare) prolonged erection of penis

nefazodone- hepatotoxicity (avoid in liver disease)

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20
Q

Vilazodone/Viibryd

Line of tx
MOA
Dosing
ADR

A

SSNRI

3rd line tx (new, less data)

MOA: serotonin reuptake inhibitor at 5-HT1A receptor-partial agonist (SPARI)

D: 10 mg x7 days -> 20 mg x 7 days -> 40 mg once daily
-take with food to increase absorption

ADR: gastrointestinal: diarrhea, nausea, vomtitin, xerostomia

neurologic: dizziness, isomnia
- CYP3A4 substrate

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21
Q

Tricyclic Antidepressant (TCAs)

MOA

A

SSNRI

MOA: inhibition of presynaptic reuptake of norepinephrine (NE) and serotonin (5-HT)
-antagonize histamine, alpha-adrenergic and muscarine receptors, cardiac sodium channels (adverse effects)

  • use fallen out of favor: OD within 1 week supply
  • poor tolerability
22
Q

SEE slide 25 for TCAs

A

25 for TCAs

23
Q

TCA adverse affects

A

SSNRI

  1. sedation
  2. decreased seizure threshold
  3. cardiovascular effects
    - orthostatic hypotension/syncope, arythmies
  4. sexual dysfunction
  5. tremor
  6. photosensitivity
  7. heat intolerance
24
Q

TCA adverse effects

3 types and examples

A
  1. anticholinergic
    - cholinergic rebound
    - srying effects: SLUD
  2. anti-histaminic
    - weight gain
    - sedation
  3. Alpha-1 Adrenergic Antagonis
    - orthostasis
    - hypotension
    - dizziness
25
Q

Monoamine Oxidase Inhibitors

line of tx
MOA

A

3rd line agent for MDD

MOA: inhibition of monoamine oxidase enzymes, MAOa and MAOb causing increased concentrations of NE, 5-HT, and dopamine (DA) in neuronal synapse

infrequently used

  • drug and food interactions, adverse effect
  • used in treatment-resistant patients
26
Q

MAOIS example

A
  1. Tranlcypromine
  2. isocarboxazid
  3. Phenelzine
  4. selegiline
27
Q

MAOIS adverse effects

A
  1. hypotension, dizziness common
  2. Anticholinergic effects (MAOIs < TCAs)
  3. hepatotoxicity (rare)
  4. sexual dysfunction
  5. cautions in cardiac disease, hepatic impairment
28
Q

Eketamine-Spravato

Indication
boxed warning

A

intranasal esketamine

I: augmentation for severe depression that failed 2 trials of antidepressants for adequate dose and duration

BW: sedation, dissociation, abuse, SI

REMS program
-must be administered by pt. in registered clinic and monitored for 2 hours after administration

29
Q

Antipsychotics in Depression

A

FDA approved agents for augmentation

  1. Aripiprazole
  2. brexpiprazole
  3. olzanzapine (only in combo with fluoxetine/symbyax)
    - quetiapine XR (seroquel XR)

*other antipsychotics may have bipolar depression indication

30
Q

Mood Stabilizers: Goal of Therapy (5)

A
  1. rapid stabilization of symptoms
  2. patient safety and wellbeing
  3. Adherence and adverse effects
  4. prevent recurrence, switching
  5. improve functioning/return to baseline
31
Q

Things to consider before rxing mood stabilizers

A
  1. are they currently taking therapy?
  2. what episode is the patient currently experiencing?
  3. What symptoms is the patient experiencing?
  4. what are patients specific factors for therapy selection?
    - other medications?
    - previous traits of success or failure?
    - comorbitities?
  5. is therapy optimized?
  6. is patient adherent?
  7. psychotic pts.
    - use antipsychotics to treat
    - can be used as mono therapy or in combination with a mood stabilizer
  8. If immediate symptom relief require
    - benzodiazepines short term
    - need for sleep and significant agitation
  9. Symptom improvement expectations
    - 7-10 days with initial mood stabilizers
    - may be less with additional therapy ~3-5 days
32
Q

Guidelines- maintenance therapy

A
  1. after ~6 months stable
  2. maintaining adherence and optimal dosage very important
    - non-adherence linked to episode frequency
    - subtherapeutic dosages may increase medication d/c
33
Q

Goals to guidelines and maintenance therapy

A
  1. relapse revention

2. early in course: restore cognitive impairment and preserve brain plasticity

34
Q

Lithium

  1. Indiation
  2. MOA
A
  1. for bipolar disorder in acute manic episodes and maintenance
    - data supports efficacy in preventing relapse and hospital admission
    - suicide- protective properties
  2. Inorganic cation that performs multiple functions within CNS ,true mechanism of action unclear
    - alters cation transport across cellular membrane
    - influences reuptake of serotonin, NE, GABA
    - postsynpatic D2 receptor sensitivity decreased
    - cAMP second messenger system
35
Q

Lithium dosing

dosage forms

A

300 mg BID-TID

increase based on serum levels and response
typical dosing range: 900-1800mg/day

consolidate dose if able

  • most commonly given BID
  • may be given once daily

Dosage forms:

  • IR capsule/tablet
  • ER/SR tablet
  • 8mgEG/5mL solution
36
Q

Lithuim pharmacokinetics

A
  1. slow accumulation in CSF; two compartment model
    - slow body distribution and delayed onset of action
    - all cellulare membranes crossed slowly
  2. Really eliminated by filtration-follows sodium no metabolism occurs
  3. Slow elimination from cells (t1/2 24 =/- 12 hrs)
    - patient may present tocos with levels in therapeutic range
  4. steady rate in 5 days
37
Q

Lithium Monitoring

A
  1. CBC, TSH weight, metabolic profile with calcium
    - 2x in first 6 months, then periodically
  2. pregnancy tests; cardiac abnormalities in 1st trimester
  3. EKG
    - baseline & annual if > 40 years old
  4. serum levels: through, steady state
    - acute mania: 0.8-1.2mEg/L
    - maintenance and elderly: 0.6-1mEg/L
    - Narrow therapeutic index: high risk drug**
38
Q

Lithium management adverse effects

A
  1. GI: take with food, divide dose, ER
  2. Hypothyroidism: elavulate for severity and clinical correlation, levothyroxine supplement 25-50mcg daily
  3. Tremor: lower dose or give smaller amounts more frequently, monitor over time for resolution, administer propranalol
  4. weigh gain: encourage diet and exercise, monitor other causes
  5. Nephrogenic Diabeters Insipidue-like syndrome: lower dose if able, give total dose at bedtime, diuretics if severe (smiloride)
39
Q

More lithium adverse effects

A
  1. memory impairment
  2. renal insufficiency
    - typically mild GFR decrease
  3. Hypercalcemia
  4. Cardiac Arrhythmias
    - T wave or ST segment abnormalities
  5. acne 33%, psoriasis 6%
40
Q

Lithium Toxicity

A
  1. can be acute/chronic
    - mild: <1.5mEg/L -> nausea, vomiting, hand tremor lethargy, diarrhea
    - moderate: 1.5-1.5 -> course hand tremor, slurred speech, unsteady gait, confusion, muscle fasciculation
    - severe (>2.5 mEg/L): seizures, stupor, coma, arrhythmia, death
  2. when to dialyze
    - >2.5 Meg,L if patient is symptomatic
    - >4.0 mEm/L regardless of symptoms

*DO NOT GIVE ACTIVATED CHARCOAL

41
Q

Lithium Drug Interactions (TALANS)

A 
Thiazides
Ace-inhibitors 
Loop diuretics
ARBs
NSAIDs
Sodium
42
Q

Valproic Adic/Divalproex: VPA

indication

MOA

dosing

A

FDA approved for bipolar disorder, acute, manic or mixed episodes

  • mechanism in bipolar disorder unclear
  • enhances GABA activity, inhibits reuptake
  • normalizes sodium and calcium channels

dosing: 10-20 mg/mg/day adjusted by level
- max 60 mg/kg/day

43
Q

VPA Monitoring

A

through serum levels after 3-5 days
-CBC, LFTs, Scr baseline, 3 months and annually

  • Hepatotoxicity-greater incidence in 1st 6 months, contraindicated in acute liver disease
  • pancreatitis
  • severe nausea/abdominal pain/anorexia
  • may be life threatening,, hemorrhagic complications
  • teratogenic: neural tube defects, VPA syndrome
44
Q

Carbamezepine (tegretol, equetro)

indication
MOA
Monitoring

A

FDA approved for bipolar disorder, actor manic or mixed episodes

MOA: blocks voltage-sensitive sodium channels, stimulated release of ADH, NMDA activity

Monitoring: CBZ serum levels at 10-14 days

  • CBC baseline, 3 months, annually
  • LFTS/electrolytes/scr/BUN baseline, 3 months, anually
  • EKG
45
Q

Carbamezepine adverse effects

A

MAJOR: **HLA-B*1502 positive risk of rash and systemic reactions

  • anemia/agranulocytosis
  • hepatotoxicity
  • systemic hypersensitivity reactions
  • fetal abnormalities in pregnancy

Minor: sedation, photosensitivity, alopecia, nystagmus, nausea/vomiting, constipation, vit D deficiency, SIAH

46
Q

Lamotrigine (Lamictal)

indication
MOA

A

FDA approved for bipolar disorder maintenance

  • used in depression as well
  • not for acute mania

MOA: blocks voltage-gated sodium channels
-decrease glutamate release

Safer in pregnancy vs. other mood stabilizers

47
Q

Lamotrigine

monitoring

Dosing

A

M: skin, CBC, LFTs, SCr baseline an annually
-dosing specific to decrease rash risk

no inducers/inhibitors: 25 mg daily x2 weeks, 100 mg daily x2 weeks, 200 mg daily x1 week, max 400 mg daily

Inudcers (phenytoin, CBZ): 50 mg daily x2 weeks, 100 mg daily x2 weeks, 200 mg daily x1 week max 400 mg daily

inhibitors: 25 mg every other day x2 weeks, 25 mg daily x2 weeks, 50 mg daily x1 week max 100 mg daily

48
Q

Lamotrigine Adverse Effects

A
  1. skin rash and SJS/TEN***
    - young age, fast titration, concomitant valproate

dizziness, ataxia, GI effects, diplopia, blurry vision, hematological rare, hepatitis, ascertain meningitis, HLH hemaphagocytic lymphohistiocytosis

49
Q

Oxcarbazepine

A

*less common mood stabilizers

  • more risk of SIADH vs. carbamezepine
  • not FDA approved for bipolar disorder
  • dosing 300 mg po bid up to 1200 mg daily
50
Q

Topiramite (topamax)

A

less common mood stabilizer

  • not FDA approved for bipolar disorder
  • causes cognitive dulling (dopamax) and can increase nephrolithiasis

Dosing: 25 mg PO BID, max 400 mg daily

51
Q

Antipsychotics

A
  1. SGAs have more clinical trial data supporting use, guideline recommended
  2. FGA have more hx data
  3. Monitoring & adverse effects smilier to treatment for other mental illnesses
    - see antipsychotics lecutre
52
Q

FDA indications for antipsychotics

A
  1. bipolar depression
    - cariprazine
    - lurasidone
    - olanzapine/fluoxetine
    - quetiapine
  2. acute manic/mixed
    - aripiprazole
    - asenapine
    - cariprazine
    - olanzapine
    - quetiapine
    - risperidone
    - ziprazidone

Psychosocial Medicine (19 decks)

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