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
2
Q
Screen Questions (SALSA)
A
- S: Sleep disturbances (insomnia with 2-4 AM awakening)
- A: Anhedonia
- LS: Low self esteem
- A: Appetite decreased
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
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
5
Q
Drugs Causing Depression
A
- Resperine: depletes biogenic amines and induces depression
- Beta blcokers: highly lipid soluble which may produce SE of depression
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
7
Q
Ketamine
A
- Infusion
- Fast and relatively sustained antidepressant effects
- Lasts 1-2 weeks
- Glutamate receptor antagonist (NMDA)
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
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
10
Q
Treatment Options
A
- TCA: autonomic, sedation SE
- SSRI: similar TCA efficacy with better SE profile (Fluoxetine/Prozac)
- SNRI (Venladaxine/Effexor)
- Serotonin Modulators (Trazodone/Desyrel, Atomoxetine/Strattera)
- MAOIs - tyramine interaction, don’t use with TCA or SSRI (Phenylzine/Nardil)
- ECT: most rapid and effective in severe suicidal depression
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
12
Q
TCA SE
A
- CV arrhythmias: NE reuptake inhibiton induces tachycardia and antimuscarinic activity blocks vagal inhibition. Conditional risk of Torsades de Pointes (QT prolongation)
- Orthostatic hypertension: due to alpha 1 antagonism
- Anticholinergic
- Sedation: antihistamine and anticholinergic
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
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
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
16
Q
SSRI SE
A
- GI distress: N/V/D, anorexia from 5HT3 agonist
- Sexual dysfunction: decreased libido, delayed orgasm (5HT3 agonist)
- CNS stimulation: agitation, restlessness, nervous (5HT2C agonist)
- Withdrawal syndrome: flu-like symptoms, N/V/D, tremors
- 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
Mirtazapine
- 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
Vilazodone
- 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
Trazodone
- 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
Vortioxetine
- Brintellix
- Serotonin Modulator
- Serotonin reuptake inhibitor
- Also acts on numerous 5HT receptors including 5HT3 and 5HT1A
29
Flibanserin
- Addyi
- Non-hormonal treatment for pre-menopausal women with HSDD
- 5HT1A agonist and 5HT2A antagonist
30
PTSD
- 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
PTSD First Line
- SNRI or SSRI
- Use with psychotherapy
- Switch to Mirtazapine and then a TCA if two trials with SSRI and SNRI are not helpful
32
Other PTSD Options
- 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
Depression + Anxiety
- 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
MAOIs
- 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
MAOIs SE
- CNS: dizziness, headache, drowsy, insomnia, seizure
| - Orthostatic hypertension: alpha2 stimulation and decreased sympathetic outflow
36
MAOI CI
- 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
Brexanolone
- 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
