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Antidepressants Flashcards

1
Q

Major (Unipolar) Depression

A
  • Cannot be related to life experiences (some exceptions)
  • Cannot experience pleasure
  • Loss of interest in normal activities
  • Insomnia
  • Loss or gain of appetite
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2
Q

Screen Questions (SALSA)

A
  • S: Sleep disturbances (insomnia with 2-4 AM awakening)
  • A: Anhedonia
  • LS: Low self esteem
  • A: Appetite decreased
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3
Q

Expanded Screening Questions (SIG E CAPS)

A

Depressed mood

  • S: Sleep decreased (insomnia with 2-4 AM awakening)
  • I: interest decreased in activity with no pleasure (anhedonia)
  • G: guilt or worthlessness (low self esteem)
  • E: Energy decreased
  • C: Concentration difficulties
  • A: Appetite disturbances or weight loss
  • P: Psychomotor retardation/agitation
  • S: Suicidal thoughts

-For diagnosis need 5 major positive answers to the above give everyday for 2 weeks

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4
Q

Monoamine Theory

A
  • Depression due to lack of 5HT and NE
  • Effective antidepressants all increase 5HT and/or NE in the synapse
  • Antidepressant effect still may take 2-6 weeks to work though
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5
Q

Drugs Causing Depression

A
  • Resperine: depletes biogenic amines and induces depression

- Beta blcokers: highly lipid soluble which may produce SE of depression

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6
Q

Neurogenesis Theory of Depression

A
  • Stress-induced decreases in hippocampal neurogenesis
  • Antidepressants increase neurogenesis over 2-6 weeks
  • Stress, genetics, growth factors all feed into this decrease
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7
Q

Ketamine

A
  • Infusion
  • Fast and relatively sustained antidepressant effects
  • Lasts 1-2 weeks
  • Glutamate receptor antagonist (NMDA)
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8
Q

Esketamine

A
  • Spravato
  • Indicated for resistant depressant with oral antidepressants
  • Intranasal, twice weekly
  • Faster onset, fewer drug interactions, less frequent dosing
  • Risk of dissociation, sedation, and abuse (CIII)
  • Must enroll into REMS
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9
Q

Genetics + Depression

A
  • Those with a close relative that is depressed are 2-3 times more likely to develop depression
  • 67-76% of identical twins will both develop depression depending on how they were raised
  • 50% of bipolar patients have a depressed parent
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10
Q

Treatment Options

A
  1. TCA: autonomic, sedation SE
  2. SSRI: similar TCA efficacy with better SE profile (Fluoxetine/Prozac)
  3. SNRI (Venladaxine/Effexor)
  4. Serotonin Modulators (Trazodone/Desyrel, Atomoxetine/Strattera)
  5. MAOIs - tyramine interaction, don’t use with TCA or SSRI (Phenylzine/Nardil)
  6. ECT: most rapid and effective in severe suicidal depression
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11
Q

TCA

A
  • 1st generation
  • Synthesized as phenothiazine variants for SCZ
  • Tertiary amine: Imipramine (Tofranil)
  • Secondary amine: Desipramine (Norpramin)
  • Blocks NE and 5HT transporters
  • Therapeutic effects takes 2-6 weeks of chronic administration
  • Also used for OCD and bed wetting
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12
Q

TCA SE

A
  1. CV arrhythmias: NE reuptake inhibiton induces tachycardia and antimuscarinic activity blocks vagal inhibition. Conditional risk of Torsades de Pointes (QT prolongation)
  2. Orthostatic hypertension: due to alpha 1 antagonism
  3. Anticholinergic
  4. Sedation: antihistamine and anticholinergic
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13
Q

Block Box: Antidepressants

A
  • Increased risk of suicidal thinking and behavior
  • Especially in children, adolescents, and young adults
  • No increased risk once 24 y.o.+ and reduced risk if 65 y.o.+
  • Monitor appropriately and closely for changes in behavior
  • Untreated depression leading to suicide is still the greater risk
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14
Q

SSRI

A
  • Approved for major depression
  • Fluoxetine (Prozac) - half life ~ 3.5 days, tapers itself in withdrawal
  • Paroxetine (Paxil) - half life ~ 1 day (withdrawal)
  • Sertraline (Zoloft)
  • Fluvoxamine (Luvox) - for OCD
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15
Q

Uses of SSRI

A
  • Major, unipolar, and bipolar depression
  • Also anxiety states including PTSD
  • Personality disorders
  • Bulimia nervosa
  • Paroxetine for hot flashes
  • Migraine prophylaxis
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16
Q

SSRI SE

A
  1. GI distress: N/V/D, anorexia from 5HT3 agonist
  2. Sexual dysfunction: decreased libido, delayed orgasm (5HT3 agonist)
  3. CNS stimulation: agitation, restlessness, nervous (5HT2C agonist)
  4. Withdrawal syndrome: flu-like symptoms, N/V/D, tremors
  5. Serotonin Syndrome: when used with drugs with 5HT activity, confusion, hypomania, twitches, tremors, severe intoxication (hyperthermia, seizure, death)

-Minimal anticholinergic, antihistamine, and alpha antagonist activity

17
Q

Venlafaxine

A
  • Effexor
  • SNRI
  • Higher doses inhibit NE reuptake
  • Lower doses act like SSRI
  • Short duration may precipitate withdrawal
18
Q

Levomilnacipran

A
  • Fetzima
  • SNRI
  • Higher selectivity for NE vs 5HT reuptake inhibition
19
Q

Nefazodone

A
  • Serzone
  • SNRI
  • Inhibits uptake of 5HT and NE
  • Antagonizes 5HT2A receptors, increasing monoamine release
  • Box warming: life-threatening hepatic failure
20
Q

Duloxetine

A
  • Cymbalta
  • SNRI
  • Treats depression, GAD, neuropathic pain, fibromyalgia, musculoskeletal pain
  • SE: Nausea, dry mouth, constipation, suicidality
21
Q

5HT Receptor Function

A
  • 5HT1A: presynaptic, agonist, antidepressive action
  • 5HT2A: postsynaptic, antagonist: enhances monoamine release to act antidepressant
  • 5HT2C: antagonist, increases appetite, weight gain (agonist: Lorcaserin/Belviq)
  • 5HT3: agonist, N/V and decreased sexual dysfunction (Antagonist: Ondansetron/Zofran)
22
Q

Atypical Antidepressants

A
  • NE and 5HT reuptake inhibitors, agonists, antagonists
  • No greater efficacy
  • Tend to have less anticholinergic, antihistamine, and CV effects
23
Q

Atomoxetine

A
  • Strattera
  • Inhibits NE transporter
  • Treats ADHD
  • Box warning: suicidal ideation in children and young adults
24
Q

Bupropion

A
  • Wellbutrin
  • Atypical antidepressant
  • MoA: weak inhibitor of NE and DA uptake
  • Treats unipolar depression, SAD, ADHD and bipolar off-label
  • Smoking cessation: Zyban, can use alone or with nicotine replacement
25
Q

Mirtazapine

A
  • Remeron
  • Atypical antidepressant
  • Enhances central noradrenergic and serotonergic activity
  • Alpha 2 antagonists which increases NE and 5HT release
  • H1 antagonists which causes sedation
  • 5HT3 antagonists, less N/V and sexual dysfunction compared to SSRI
  • 5HT2C antagonist: weight gain
26
Q

Vilazodone

A
  • Vibryd
  • Serotonin modulator, 1st of its class
  • Dual acting serotonergic antidepressant
  • 5HT reuptake inhibitor and partial 5HT1A receptor agonist
  • May work faster with duel mechanism
  • AE: N/D
  • Warning: suicidal risk and serotonin syndrome
27
Q

Trazodone

A
  • Desyrel
  • Serotonin modulator
  • Metabolite (mCPP) is 5HT1A agonist and 5HT2A antagonist
  • Increases 5HT1A neurotransmission and leads to antidepressant activity
  • High incidence of sedation from H1 antagonism
  • Little anticholinergic or CV effects
28
Q

Vortioxetine

A
  • Brintellix
  • Serotonin Modulator
  • Serotonin reuptake inhibitor
  • Also acts on numerous 5HT receptors including 5HT3 and 5HT1A
29
Q

Flibanserin

A
  • Addyi
  • Non-hormonal treatment for pre-menopausal women with HSDD
  • 5HT1A agonist and 5HT2A antagonist
30
Q

PTSD

A
  • Discouraged use of benzos
  • Encourage treating acute pain aggressively
  • Re-experience events that involve potential or actual injury or death
  • Hyperarousal, numb to feelings, relationships, experiences
  • Address suicide risk and signs of violence BEFORE starting treatment
31
Q

PTSD First Line

A
  • SNRI or SSRI
  • Use with psychotherapy
  • Switch to Mirtazapine and then a TCA if two trials with SSRI and SNRI are not helpful
32
Q

Other PTSD Options

A
  • Atypical antipsychotics to use with antidepressants
  • Prazosin for nightmares
  • Benzos for insomnia nad anxiety, may worsen fear response
  • Analgesia to reduce pain form traumatic injury and therefore reduce risk of developing PTSD
33
Q

Depression + Anxiety

A
  • Occur together in approximately 45-75%
  • Negative affect found in both, but panic attacks are unique to anxiety and dysphoria was more associated with depresion
  • SSRI, SNRIs can be used to treat depression AND anxiety
  • Take 3-6 weeks to take effect, but benzos have a more rapid control
  • Longer half life benzos have less withdrawal like clonazepam or alprazolam XR
  • Avoid benzos in those with substance abuse and taper patients off of themt o minimize withdrawals
34
Q

MAOIs

A
  • Phenelzine (Nardil)
  • Tranylcypromine (Parnate)
  • IRREVERSIBLY bind to MAO receptors
  • Analogs of amphetamine
  • Takes 2-3 weeks for therapeutic effect
  • MAO-A inhibition increases NE and 5HT (depression)
  • MAO-B inhibition increases dopamine (Parkinsons), ex: selegiline)
35
Q

MAOIs SE

A
  • CNS: dizziness, headache, drowsy, insomnia, seizure

- Orthostatic hypertension: alpha2 stimulation and decreased sympathetic outflow

36
Q

MAOI CI

A
  • Hypertensive crisis: potentially fatal elevations in BP especially when used with sympathomimetics (ephedrine, PSE, NE, EPI, DA, L-DOPA)
  • Serotonin syndrome: MAOI + any serotonergic compound
37
Q

Brexanolone

A
  • Zulresso
  • Treats postpartum depression
  • Restores level of progesterone metabolite that dips around childbirth (allopregnanolone)
  • IV, given continuously over 60 hours, takes 1-2 days to work
  • Mech: normalizes GABA-A receptor activity
  • Black box: excessive sedation or sudden loss of consciousness, must enroll into REMS program

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