Anti Depressants

Front 1

Unipolar depression is a leading cause of disability. More prevalent in which gender?

Back 1

Female

Front 2

First degree relatives of ppl w/ depression are 1.5-3x ___ likely to have depression. The ____ serotonin transporter gene is protective.

Back 2

1. more
2. long

Front 3

What drug can induce MDD?

Back 3

Reserpine by depleting 5HT and NE In synaptic cleft

Front 4

How does electroconvulsive therapy help to tx depression?
What does ECT essentially induce?
What kind of depression is this appropriate for?

Back 4

1. by rapid down regulation of B receptors
2. induce grand mal seizure
3. good for SEVERE depression w/ psychosis and catatonic features refractory to tx

Front 5

Down regulation of which receptors is correlated w/ improvement in sx?

Back 5

downregulation of B receptors

Front 6

What are the 2 main sx, at least one of which must be present to dx depression? Other sx include:, what is the mnemonic

Back 6

1. depressed mood
2. anhedonia
- Weight loss or gain of more than 5% in one month
- Insomnia or hypersomnia
- Psychomotor agitation or retardation
- Fatigue or loss of energy
- Feelings of worthlessness/inappropriate guilt
- Difficulty concentrating /indecisiveness
- Thoughts of death/suicidal ideation
- SIGECAPS
- sleep, interest, gult, energy, concentration, appetite, psychomotor, suicide

Front 7

What must be r/o before making MDD dx?
What lab tests should be performed?

Back 7

1. manic or hypomanic episodes-- i.e. bipolar disorder, drug induced depression, and fam hx
2. CBC, thyroid panel (hypothyroidism), B12, also r/o substance abuse

Front 8

Is IPT or CBT effective for severe depression w/ psychosis?
What is psychotx good for?

Back 8

1. not as effective as meds
2. good to prevent relapse

Front 9

Meds have more ___ response but when discontinued have risk of ____.

Back 9

1. rapid
2. relapse

Front 10

1. NE is ass w/ ___, high ___, and motivation for ____
2. 5HT modulates ___, sleep, ____, ___, and obsessional thoughts
3. DA helps w/ ____, atten, and _____

Back 10

1. focused attention, energy, and motivation for reward
2. mood, sleep, appetite, anxiety, and obsessional thoughts
3. joy of life, attn, and euphoria/pleasure

Front 11

5HT3 receptors are found mainly in the ____.
5HT3 receptor agonists cause-->
5HT3 antagonists cause-->

Back 11

1. gut
2. agonists cause N&V, and diarrhea
3. antagonists-have anti emetic properties

Front 12

5HT2 receptor agonists cause--
1.
2.
3.
4. (this SE is NOT transient)
5HT2 receptor antagonists have what effect?

Back 12

1. insomnia
2. anxiety
3. akathesia
4. sexual dysfunction which is NOT a transient SE, while the rest are
5. 5HT2 receptor antagonists improve the above SE and also help to decrease sexual dysfunction

Front 13

1. H1 antagonist-- leads to ___ and sedation
2. Muscarinic antagonists (anticholinergics)-
3. alpha 1 antagonist-

Back 13

1. wt gain
2. dry mouth, constipation, drowsiness, confusions
3. orthostatic hypotension

Front 14

TCAs- MOA- immediate and chronic response?
How long does it take to see full effect?

Back 14

- block the reuptake of 5HT and NE
- immediate action is to increase NE and 5HT in synaptic cleft
- after chronic tx- beta NE receptors are downregulated adn 5HT2 receptors are downregulated
- also there is sensitization of the 5HT receptors
- therefore it takes 4-6 wks to see the full effects of TCAs

Front 15

TCAs- drug names, AE

Back 15

1. Desipramine, and Nortriptyline are commonly used b/c have less SE then imipramine adn amitriptyline
2. AE:
- anticholinergic (urinary retention!, constipation, dry mouth, blurred vision, and memory impairment),
- sedation and wt gain by histamine antagonism,
- orthostatic hypotension by alpha adrenergic antagonism, and
- cardiotoxicity by Na channel blockade- prolong QT interval
- also sexual dysfunction- loss of libido, anorgasmia
- also will lower sz threshold
- also may cause birth problems- CI in pregnancy

Front 16

For tertiary TCAs such as amitriptyline adn Imipramine what are names of the secondary amines which these drugs are metabolized to?

Back 16

1. nortriptyline
2. despipramine
3. rem these secondary amines have less SE than the tertiary amines

Front 17

TCAs should not be used in pts w/ ___ diseases or ___ disorders

Back 17

1. cardiac diseases- QT prolongation, should no be used in pts post MI, CABG,
2. seizure disorders- these drugs lower the seizure threshold so should not be used in such pts

Front 18

TCAs- Use, CI

Back 18

- Useful for pts w/ NEUROPATHIC pain, migraine, and fibromyalgia
- fatal OD lims use, is alt for pts w/ mod to severe depression who cannot use SSRI or other antidepressant
- should not be used in pts w/ CHD, BPH, dementia, costipation, those at risk for seizures, and the very elderly (b/c of ortho htn)
- causes birth problems though not a teratogen- try not to use in pregnant pts

Front 19

MAOIs- MOA

Back 19

- block the enzyme responsible for breakdown of biogenic amines in the presynaptic neuron inlcuding NE, 5HT, DA, epi, and tyramine
- two different enzymes are involved MAO A and MAOB
- MAOA- NE, 5HT, and tyramine
- MAO B- DA-- helpful for parkinsons

Front 20

Phenelzine, oscarboxazid, and tranylcypromine- PK
Selegiline- MOA, PK

Back 20

1. irreversible and nonselective MAO inhibitor
2. Selective MAO B inhibitor, avaialbe in skin patch formulation (Emsam) for depression

Front 21

MAOI- AE

Back 21

- potentially fatal interaction w/ tyramine rich foods such as wine and cheese- b/c MAO A inhibition causes increase in available tyramine- tyramin3 initiates release of noradrenaline- which may cause hypertensive crisis
- common- sleep disturbance, orthostatic hypotension, sexual dysfunction, and wt gain

Front 22

MAOI- DI, what sig does this have when switching a pt from another antidepressant to MAO I?

Back 22

1. significant DI w/ any other antidepressant or any drug metab by MAO-- meperidine, dextromethorphan, sympathomimetics, and phenylephrine
- can lead to serotonin syndrome or xs sympathimimetic activity
2. when switching a pt to MAOI must wait for 2 wks after disocntinuing first antidepressant before giving MAOI, xcept for fluoxetine w/ which you should wait 5-6 wks

Front 23

When are nonselective mAOIs used?

Back 23

- used for atypical depression characterized by hypersomnia, wt gain, and/ or mood reactivity
- SSRIs or others are used first

Front 24

SSRI-MOA

Back 24

- SSRIs block reuptake of serotonin thus causing the concentration in the synaptic cleft to be increased

Front 25

SSRIs- AE

Back 25

- b/c there are different subtypes of serotonin receptors there are different types of AEs
- restlessness (5HT2 agonist activity), insomnia, GI disturbance(5HT3 agnoist activity)which are transient
- sexual dysfunction - 5HT2 agonistic activity-- which are NOT transient

Front 26

- Fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram- Class
- Fluoxetine- PK

Back 26

Class: SSRI
Fluoxetine (prozac)- PK- active metabolite stays around for 7-9 days - good for pts w/ compliance issues

Front 27

Fluoxtine and paroxetine- Class, DI
Which drugs of the same class are preferred b/c of low DIs?

Back 27

Class: SSRI
DI: inhibit liver enzymes- P450-2D6
- Paroxetine>norfluoxetine>fluoxetine > sertraline>citalopram

- sertraline and citalopram

Front 28

What effects are seen when SSRIs or SNRIs are combined w/ other drugs that affect serotonin?

Back 28

- cog/behavioral-- confusion, HA
- auto nervous sys- hyperthermia, sweating, htn, diarrhea, tachycardia
- neuromusc- hyperreflexia, myoclonus, muscle rigidity

Front 29

W/ SSRI induced sexual dysfunction what has been helpful?

Back 29

- sildenafil

Front 30

What happens if an antidepressant is abruptly discontinued, esp those w/ short half lives?
Describe the sx.

Back 30

1. Discontinuation syndrome
2. electric shock sensations, anxiety, N, HA, flu like sx
- drugs like paroxetine and vanflaxine-- have very short half lives

Front 31

Fluoxetine- Class, preferred in pts w/ psychomotor ___ and should be dosed in the morning
Paroxetine - Class, preferred in pts w/ psychomotor ____ and should be at bedtime

Back 31

Class: SSRI
- fluoxetine- for pts w/ psychomotor retardation
- paroxetine for pts w/ psychomotor activation

Front 32

SSRI- Use

Back 32

- DOC for depression, inexpensive except sertraline
- DOC for depression w/ comorbid anxiety- even though at the BEGINNING of tx pts may feel a little bit more anxiety

Front 33

SNRI- Venlafaxine- MOA

Back 33

- serotonin and NE reuptake inhibitor
- NE and 5HT reuptake inhibitor, initially more of 5HT is affected more, then later NE is affected as well
- unlike TCAs has negligible effects at other receptors that cause anticholinergic or antihistamine adverse effects

Front 34

SNRIs- AE

Back 34

- sim to SSRIs at lower doses b/c venlafaxine works primarily as SSRIs at low doses
- SE related to NE more pronounced at higher doses- b/c NE reuptake inhibition at higher doses - htn (usually not clinically sig unless pt has uncontrolled htn)
- Duloxetine- liver toxicity
- abrupt discontinuation can lead to withdrawal syndrome

Front 35

SNRIs- USe

Back 35

- has faster response and higher remission rates
- Venlafalzine- avoid in pts w/ uncontrolled htn
- Duloxetine- can be used in pts who have depression w/ pain-- diabetic neuropathy

Front 36

Duloxetine- Class, Use, MOA, DI, AE

Back 36

Class: SNRI
Use: Expensive for depression, also used for diabetic peripheral neuropathy, chronic back pain and OA- good for pts w/ depression adn neuropathic pain
DI: CYP2D6 inhibitor
AE: liver toxicity
MOA: has equal reuptake inhibition of both NE and 5HT across the entire dose range

Front 37

Trazodone- MOA, AE

Back 37

- This drug is a serotonin reuptake inhibitor that also blocks 5-HT2A receptors
- use at bed time, used as adjunct to an SSRI in pts w/ insomnia
AE: It does not cause the anticholinergic or cardiotoxic effects like TCAs, but still causes orthostatic hypotension. It is also very sedating
- It is important to be aware of the potential for priapism (1 in 6000 males)-prolonged erection that needs to be txed w/ surgical drainage.

Front 38

Nefazodone- Class, Use

Back 38

Class: Also a 5-HT2A antagonist, but blocks the reuptake of both 5-HT and NE. Some have referred to this class as serotonin antagonist reuptake inhibitors (SARIs) (5-HT2A antagonist/reuptake inhibitor).
Use: 5-HT2A blocking activity may make this drug: More effective for relief of depression-related anxiety and insomnia
- Less likely to experience drug-induced sexual dysfunction

Front 39

Nefazodone- AE, DI,

Back 39

- sedation, GI, dry mouth, constipation
- liver toxicity DEADLY
DI: CYP3A4 inhibitor

Front 40

BUproprion- Class, MOA

Back 40

- Class: NDRI
- primarily inhibitor of DA and NE reuptake w/ little effect on 5HT

Front 41

Bupropion- SE, CI

Back 41

- psychomotor activation
- anxiety, HA, and insomnia
- can also cause psychosis
- inhibits appetite
- INCREASED RISK OF SZ
- CI: pts who are sz susceptible- head injury, bulimia,

Front 42

Buproprion- Use

Back 42

- not good for pts w/ comorbid anxiety
- less problem w/ sexual dysfunstion
- may lead to wt loss
- good fro pts that cannot tolerate sedation, wt gain, or sexual dysfunc
- also helps w/ smoking cessation

Front 43

Mirtazapine- MOA

Back 43

- antagonism of presyn auto receptors (alpha 2) which results in increase in NE and 5HT in synapse
- also drug blocks 5HT2, 5HT3, and H1 receptors
- rem 5HT2 recept antag-- least AD induced sexual dysfunction and anxiety
- 5HT3 receptor antagonist-stops nausea
- H1 antagonist- increased appetite, and wt gain, sedations-- give at bedtime

Front 44

Mirtazapine- SE, Use

Back 44

- pronounced sedation and sig wt gain
- good for pts w/ insomnia or unintentional profound wt loss
- small rare neutropenia and agranulocytosis
Use: good if pt has insomnia and anorexia as well, NO sexual dysfx, also good if pt has comorbid anxiety

Front 45

Symptom remission w/ antidepressants
In first wk will note __ and __- disturbances begin to improve.
In 1-3 wks-
In 3-6 wks

Back 45

1. sleep and appetite
2. increased energy, sex drive, self care, and memory, sleeping/eating normalize, and thinking normalizes
3. relief of depressed moods, less hopelessness, and thoughts of suicide subside

Front 46

What is the goal of the first phase or short term tx?
What is the goal of the second phase or continuation tx?
What is the goal of the third phase or maintenance tx?

Back 46

1. resolve sx- 6-12 wks
2. keep sx in remission-- 4-9 mos
3. long term tx may be required in pts at high risk for relapse-- i.e. pts w/ prior hx or fam hx

Front 47

What does response mean?
What does remission mean?

Back 47

1. 50% reduction in sx
2. complete resolution of depressive sx and a return to normal functioning

Front 48

If pt fails to achieve remission what should be the first step? Then?

Back 48

1. switch to another antidep w/ tapering of first
2. augmentation

Front 49

What are safe therapies for pregnant depression pts?

Back 49

- Psychotherapy and ECT
- largest body of evidence for fluoxetine--SSRI
- TCAs not horrible
- paroxetine-CONTRAINDICATED