Depresion And Mood Disorders

Front 1

What are the most common mental illnesses? Each affect what % of the population?

Back 1

Mood and anxiety disorders are the most common mental illnesses, each affecting up to 10% of the general population at some time in their lives.

Front 2

Depression afflicts how many adults in the US annually?

Back 2

14 million

Front 3

What is the % In children, prevalence of mood disorders in US ?

Back 3

> 25%

Front 4

Prescribing rates for drugs to treat psychiatric disorders accounts for what % of all prescriptions written in the US?

Back 4

15%

Front 5

What are the 5 challenges in the depression and mood disorder field?

Back 5

Challenges in the field:
Underlying pathogenesis of psychiatric disorders not well understood.
Animal models do not represent human disease.
Overlapping symptomology across disease states.
Heterogeneous patient groups and subjective clinical endpoints.
Paucity of clinical data in children

Front 6

What are 6 side effects of depression?

Back 6

1.Intense sadness, hopelessness and despair 2.inability to experience pleasure in usual activities 3.changes in sleep patterns and appetite 4.loss of energy, body pain, endocrine changes 5.suicidal thoughts. 6.Above and beyond normal grief and disappointment

Front 7

What is Mania?

Back 7

opposite of depression

Front 8

what are 3 side effects of mania? What is not a side effect?

Back 8

1.Enthusiasm, euphoria, high energy 2.Rapid thought and speech patterns 3.Extreme self-confidence and impaired judgment

NOT schizophrenia (disturbed thought and hallucinations)

Front 9

What are 3 therapeutic options for depression?

Back 9

1. Electroconvulsive therapy (ECT)
2.Herbal Remedies
3.Antidepressant Drugs

Front 10

The FDA requires all antidepressants to carry what?

Back 10

a black box warning stating that antidepressants may increase the risk of suicide in persons younger than 25.

Front 11

The antidepressant black box warning is based on what?

Back 11

based on statistical analyses conducted by two independent groups of FDA experts that found a 2-fold increase of the suicidal ideation and behavior in children and adolescents, and 1.5-fold increase of suicidality in the 18–24 age group.

Front 12

Most antidepressants, either directly or indirectly have what kind of effects? Particularly where?

Back 12

potential the effects of monoamine neurotransmitters and their receptors, particularly norepinephrine and/or serotonin

Front 13

Do they alter moods in healthy subjects?

Back 13

no

Front 14

What is the Biogenic amine theory

Back 14

simplistic theory that depression due to deficiency of monoamines at certain key sites in the brain. Opposite is true for mania.

Front 15

What is the time course of therapeutic response in antidepressants?

Back 15

weeks vs hours

Front 16

It is possible that ↓ neurotransmitter uptake is only what kind of effect? May not be directly responsible for what?

Back 16

initial effect of the drugs and may not be directly responsible (or sufficient) for antidepressant efficacy

Front 17

What is MAO? Where is it found?

Back 17

MAO is mitochondrial enzyme found in tissues including nerves, liver and GI tract

Front 18

In neurons what is MAO?

Back 18

, MAO is a “safety” switch  oxidatively deaminates( removal of an amine group from a molecule) and inactivates excess neurotransmitter molecules that may leak out of synaptic vesicles when neuron is at rest

Front 19

Monoamine oxidase inhibtors (MAOI),have what 2 therapeutic uses?

Back 19

1.Depressed patients unresponsive (or allergic) to other Rx or who have strong anxiety, phobia or low psychomotor activity
2.Atypical depression: labile mood, rejection sensitivity and appetite disorder

Front 20

What are 3 MAOI Drugs?

Back 20

Phenelzine, Selegiline, Tranlcypromine

Front 21

MAOI's may do what to the enzyme? Where does it accumulate and leak into? What does it activate? What are its indirect effects?

Back 21

MAOIs may irreversibly or reversibly inactivate the enzyme --> accumulation of neurotransmitters in pre-synaptic neuron and leaks into synaptic space -->activation of norepi and serotonin receptors ->indirect anti-depressive effects

Front 22

MAOIs form what kind of complexes with what? What does it cause?

Back 22

Most form stable complexes with the MAO enzyme causing irreversible inactivation.

Front 23

Where do MAO effect? High incidence of what?

Back 23

Effect MAO not only in brain, but also in liver and GI tract --> high incidence of DDI and drug-food interactions

Front 24

Tyramine is what kind of substance? What does MAO do to it?

Back 24

Tyramine, a potentially toxic substance found in certain foods, is normally oxidatively deaminiated by MAO

Front 25

How long does it take for MAO to be fully inhibited? How long for the anti-depressant activity?

Back 25

MAO is fully inhibited within a few days of treatment however the anti-depressant activity is delayed by several weeks.

Front 26

Selegiline and tranycypromine also have what kind of effects? What 2 things can they also cause?

Back 26

tranycypromine also have amphetamine-like stimulant effects --> agitation and insomnia

Front 27

How are MAOIs absorbed? How long before efficacy? How are they cleared? When does enzyme regeneration occur?

Back 27

1.Well absorbed orally but require weeks for efficacy
2.Metabolized and rapidly cleared (renal)
3.Enzyme regeneration (irreversibly inactivated) occurs several weeks following termination of Rx

Front 28

How long of a delay from time patient stops MAOI Rx before switching to another antidepressant from any other class

Back 28

Minimum 2 weeks

Front 29

MAOI Inhibit degredation of what? What does this increase the release of? What are 4 very serious side effects because of that?

Back 29

MAOI inhibit degradation of tyramine (aged cheeses and meats, red wines, pickled and smoked fish)--> increase catecholamine release. Leads totachycardia, seizures, hypertension, stroke

Front 30

What are 5 adverse effects of MAOI?

Back 30

Orthostatic hypotension, drowsiness, blurred vision, dry mouth, dysuria constipation

Front 31

Should MAOI and SSRIs be co-administered?

Back 31

NO-->serotonin syndrome

Front 32

What should the wash-out period be for MAOI and SSRIs? What should be taken before MAOI Rx? How long for?

Back 32

Minimum 2 week wash-out period; minimum 6 weeks for fluoxetine prior to MAOI Rx

Front 33

What is a Valuable alternative for SSRI non-responders?

Back 33

Tricyclic Antidepressants

Front 34

What are 3 tricyclic antidepressant drugs?

Back 34

Imipramine, Amitriptyline, Amoxapine

Front 35

Tricyclic antidepressants MOA is the inhibition of what? What are the Transporters?

Back 35

Inhibition of neurotransmitter (nor-epi and serotonin) reuptake into the neuron (Transporters: NERT and SERT)

Front 36

Tricyclic antidepressants increase concentration of what, where? What don't they block?

Back 36

Increase concentration of monoamines at the synaptic cleft.
Do not block dopamine transporters at therapeutic concentrations.

Front 37

Tricyclic antidepressants are ____ to other receptors? What are the 3 receptors?

Back 37

Antagonist of other receptors: alpha-adrenergic, H1 and muscarinic

Front 38

What are 3 tricyclic antidepressant drugs?

Back 38

Imipramine, Amitriptyline, amoxapine

Front 39

When taking TCA for long term what happens?

Back 39

adaptation to drug

Front 40

Initial blockade of NE reuptake by TCA initiates what?

Back 40

a series of neuronal alternations

Front 41

when Chronic TCA Rx results in adaptation to the drug, what is enhanced? Over time what becomes more sensitive to what?(What does this enhance? What 2 receptors are decreased? What is normailized?

Back 41

1.Enhanced NE and 5-HT neurotransmission over time. 2.Over time (weeks), alpha-1 adrenergic receptors become more sensitive to NE stimulation. 3.Enhances overall effect of NE (beyond increasing NE signal at the synapse) 4.↓ GABA-B receptors, ↓ NMDA receptors 5. Normalization of glucocorticoid release and sensitivity

Front 42

What do SSRI specifically inhibit? What do they have long term effect on?

Back 42

1.specifically inhibit serotonin re-uptake (acute and chronic effects) 2.Long term effect on 5-HT1 a receptors (desensitization of inhibitory R)

Front 43

What is the fold of SSRI selectivitey for SERT vs. NERT?

Back 43

300-3000 fold

Front 44

SSRI have little effect on what?

Back 44

dopamine transport

Front 45

SSRI have minimal interaction with what? What does it improve compared to TCAs?

Back 45

Minimal interaction with muscarinic, alpha-adrenergic and H1 receptors--> improved side effect profile vs. tricyclic antidepressants.

Front 46

SSRIs have largely replaced what? Why?

Back 46

SSRIs have largely replaced tricyclic antidepressants and monoamine oxidase inhibitors as drugs of choice for treating depression.Because of fewer adverse side effects and relative safety upon overdose,

Front 47

What are 3 SSRI drugs?

Back 47

1. Sertraline (zoloft)
2.Paroxetine (Paxil)
3.Fluoxetine (prozac)

Front 48

SSRI and TCA decrease regulation of what? increase release of what? Increase what kind of activity? What does it lead to?

Back 48

↓ Regulation pre-synaptic inhibitory receptors →↑ NT release
↑ post-synaptic receptor activity → therapeutic response

Front 49

What SSRI drugs are sedating for sleep disturbances? What 2 drugs are activating?

Back 49

1.Paroxetine and flucoxamine
2.sertraline and fluoxetine

Front 50

What are 4 SSRI side effects?

Back 50

Sleep disturbances
Anxiety and agitation
GI upset
Sexual dysfunction

Front 51

Overdose of SSRI may cause what?

Back 51

: may cause seizures; low incidence of cardiac arrhythmia vs. TCA

Front 52

What are SSRI use in children an teens? What is essential?

Back 52

used with caution in children as 1 in 50 children become more suicidal w/SSRI treatment. Close monitoring essential.

Front 53

What syndrome can SSRI cause? Describe it?

Back 53

Serotonin syndrome: Potentially life-threatening syndrome from excess serotonergic activity in CNS due to over-dose, DDI, or recreational drug use.

Front 54

What is discontinuation syndrome?

Back 54

Withdrawal symptoms experienced by some patients upon abrupt cessation or significant dose reduction of antidepressant mediations

Front 55

Discontinuation syndrome is more prevalent with drugs that have what? What are these 2 drugs? How long can it last for?

Back 55

More prevalent w/drugs that have short t1/2
SSRIs
SNRIs
Can last days → weeks

Front 56

Selective Serotonin/Norepinephrine Re-uptake Inhibitors (SSNRI) may be effective in what patients?

Back 56

May be effective in patients that do not respond to SSRIs

Front 57

SSNRI have some efficacy in treating what?

Back 57

efficacy in treating backache and muscle ache pain associated with depression as well as treating neuropathic pain (diabetic neuropathy).

Front 58

SSNRI, unlike TCAs have little activity against what? This leads to fewer what compared to TCA?

Back 58

Unlike TCAs, have little activity against adrenergic, muscarinic or H1 receptors → fewer adverse side effects than TCAs

Front 59

What syndrome is observed when SSNRI are abruptly stopped?

Back 59

discontinuation syndrome

Front 60

What are 2 SSNRI drugs?

Back 60

Duloxetine (Cymbalta)
Venlafaxine (Effexor)

Front 61

What are 2 examples of Atypical Antidepressants?

Back 61

Bupropion (Welbutrin)
Mirtazapine

Front 62

Buproprion is a weak what? What kind of inhibitor? What kind of T1/2

Back 62

weak nor-epi and dopamine reuptake inhibitor

Short t1/2

Front 63

What does Buproprion decrease? What receptor is involved with it?

Back 63

Decrease craving and withdrawal symptoms of nicotine addiction (smoking cessation)

alpha3β4 Nicotinic acid receptor antagonist

Front 64

Bupropion has what kind of DDI risk? What are adverse effects?

Back 64

Low risk of DDI
Dry mouth, sweating, nervousness, tremor, seizures at high doses, very low incidence of sexual dysfunction

Front 65

Mirtazapine is what kind of drug? What does it enhance? By blocking what? What else does it block?

Back 65

TCA; enhances serotonin and nor-epi neurotransmission via blocking presynaptic 2 receptors. Also blocks 5-HT2 receptors.

Front 66

Is Mirtazapine sedating? what side effects doesn't it have? What side effect is increase what can it lead to?

Back 66

Sedating (H1) but no anti-muscarinic or sexual side effects.
Increased appetite and weight gain.

Front 67

What are the most common therapies for clinical anxiety?

Back 67

Benzodiazepines and SSRIs

Front 68

When are SSRIs used in patients instead of benzos?

Back 68

SSRIs are often used instead of benzos in patients with concerns for addiction or dependence, or history of addiction or dependence to other substances.

Front 69

Some patients with panic disorders respond to which class of drugs?

Back 69

TCAs

Front 70

MAOIs can be particularly effective in treating patients experiencing what? Why is it considered last-line Rx?

Back 70

strong anxiety or phobic states.

due to risk for DDI and drug-food interactions

Front 71

what are commonly prescribed for pediatric anxiety (instead of benzos)?

Back 71

SSRIs

Front 72

The antidepressants Anafranil, Luvox and Zoloft have FDA indications for children and adolescents in the treatment of what?

Back 72

OCD

Front 73

Clinical experience with Prozac, Zoloft, Celexa & Lexapro -- in controlled pediatric studies has led clinicians to consider these agents for treating what as well?

Back 73

non-OCD anxiety disorders as well.

Front 74

What kind of response to benzos do children have?

Back 74

Paradoxial (anxiety, agitation)