Drug for Depression & Anxiety

Question 1

Locations of the neuron circuitry regulating anxiety and fear

Answer 1

subcortical (subconscious)

Question 2

Fear

Answer 2

an emotional state aroused by specific external stimuli that gives rise to defensive and escape behaviours

Question 3

Anxiety

Answer 3

a generalized response to an unknown threat or internal conflict. Some argue that anxiety occurs when a person recognizes that they are not in control of the outcome of a threatening situation

Question 4

bilateral degeneration of amygdala

Answer 4

patient lives without fear

Question 5

Anxiety Disorders

Answer 5

psychiatric conditions characterized by overactivity of the autonomic nervous system, expectation of an impending threat and continuous vigilance of danger (not caused by drug intoxication or withdrawal)

Question 6

Panic disorder

Answer 6

Episodic periods of intense fear and ANS over activation (fast heartbeat, short breath & patients sincerely think they are dying)

Question 7

Generalized anxiety disorder

Answer 7

Persistent state of excessive worry and anxiety serious enough to cause a disruption in normal activities

Question 8

Anticipatory anxiety

Answer 8

A fear of having a panic attack; may lead to agoraphobia

Question 9

Agoraphobia

Answer 9

A fear of being away from home or another protected place

Question 10

Social anxiety disorder

Answer 10

Excessive fear of being exposed to the scrutiny of other people that lead to avoidance of social situations

Question 11

Post-traumatic stress disorder

Answer 11

A reaction to a terrifying event that occurs to or is witnessed by the patient. Characterized by flashbacks, nightmares, anxiety and compulsive thoughts about event

Question 12

lifetime prevalence of anxiety disorders

Answer 12

20 % (most prevalent psychiatric condition)

Question 13

Biological causes of anxiety disorders

Answer 13

• Females 2x as likely as males to develop an anxiety disorder.
• but heritability is low compared to other psychiatric conditions (0.3).
• major factors are environmental & not genetic

Question 14

Brain regions important in Anxiety

Answer 14

• Amygdala
• Hypothalamus
• Anterior pituitary
• Adrenal gland

Question 15

Cortisol (stress)

Answer 15

causes immune suppression, weight gain & causes some of synapse connections to detach & disappear (especially in hippocampus)

Question 16

adrenal gland

Answer 16

produces adrenaline & cortisol

Question 17

First-line pharmacotherapy for anxiety disorders

Answer 17

SSRIs (selective serotonin reuptake inhibitors)

Question 18

fMRI

Answer 18

functional magnetic resonance imaging
*used to measure changes in blood flow - more neuron activity = more blood

Question 19

the brain of patients with anxiety disorders show…

Answer 19

an over activation of the amygdala

Question 20

DTI

Answer 20

diffusion-tensor imaging

Question 21

GAD and PD can also be treated with…

Answer 21

Benzodiazepines (at low dose)
but have limitations due to tolerance, withdrawal, rebound effect, abuse liability

Question 22

Disability is measured in:

Answer 22

DALY = How many years of healthy life are lost to the disease

Question 23

Major Depressive Disorder (MDD)

Answer 23

1. Depressed mood most of the day.
   
   2. Diminished interest or pleasure in all or
      most activities.
   3. Significant unintentional weight loss or
      gain.
   4. Insomnia or sleeping too much.
   5. Agitation or psychomotor retardation
      noticed by others.
   6. Fatigue or loss of energy.
   7. Feelings of worthlessness or excessive
      guilt.
   8. Diminished ability to think or concentrate,
      or indecisiveness.
      
      9. Recurrent thoughts of death.

Question 24

MRI

Answer 24

used to measure brain volumes and detect lesions and malignancies Volume loss thought to reflect loss of synapses or less neurogenesis in MDD

Question 25

Heritability of Depression

Answer 25

0.3-0.4 = 30-40% of risk is due to genetic factors

Question 26

Medial prefrontal cortex (of those with depression)

Answer 26

Increased functional activity Lower volume

Question 27

Lateral prefrontal cortex (of those with depression)

Answer 27

Decreased functional activity Lower volume

Question 28

Striatum (of those with depression)

Answer 28

Decreased functional activity Lower volume

Question 29

Amygdala (of those with depression)

Answer 29

Increased functional activity Same volume

Question 30

Hippocampus (of those with depression)

Answer 30

Increased functional activity Lower volume

Question 31

Low Brain Derived Neurotrophic Factor (BDNF) is caused by

Answer 31

Depression - less dendritic sprouts

Question 32

5 primary Monoamines

Answer 32

1. dopamine (DA) 2. norepinephrine (NE) 3. serotonin (5HT) 4. Melatonin 5. Histamine

Question 33

Monoamines regulate

Answer 33

mood, sleep, appetite, peristalsis, arousal, sexual function, cognition, reward, motivation, aggression – sometimes with opposing effects between dopamine and serotonin.

Question 34

7 Treatments for depression

Answer 34

1. Psychotherapy - cognitive behavioral therapy 2. Tricyclic antidepressants (TCA’s) 3. Monoamine oxidase inhibitors (MAOi’s) 4. Selective Serotonin Reuptake Inhibitors (SSRI’s) 5. Serotonin/Norepinephrine Reuptake Inhibitors (SNRI’s) 6. Hallucinogens (ketamine, psilocybin, MDMA) 7. Electroconvulsive therapy (ECT & TMS)

Question 35

SNRIs

Answer 35

Venlafaxine (Effexor) duloxetine (Cymbalta) - blocks (antagonizes) both SERT and NET.

Question 36

Bupropion (Wellbutrin)

Answer 36

little action at SERT, but blocks DAT and NET. So not an SSRI or a SNRI – in a class of its own.

Question 37

Fluoxetine (Prozac)

Answer 37

least selective, first line for adolescents

Question 38

Paroxetine (Paxil)

Answer 38

anti-cholinergic effects, most weight gain

Question 39

Citalopram (Celexa)

Answer 39

most selective for SERT

Question 40

Sertraline (Zoloft)

Answer 40

also antagonist of DAT (dopamine transporter)

Question 41

SERT

Answer 41

serotonin transporter

Question 42

NET

Answer 42

norepinephrine transporter

Question 43

Monoamine Oxidase Inhibitors

Answer 43

removes the neurotransmitters norepinephrine, serotonin and dopamine from the brain.

Question 44

Serendipitous

Answer 44

discovery that a drug for tuberculosis patients had antidepressant effects

Question 45

Phenelzine

Answer 45

irreversible inhibitor of monoamine oxidase – once it binds the enzyme it permanently inactivates it and there is no more enzyme until the cell makes more - Highly effective

Question 46

Negative side effects of Phenelzine

Answer 46

numerous drug-drug interactions that cause hypertensive crisis (too much adrenaline) & serotonin syndrome (too much serotonin) that can be fatal

Question 47

Tricyclic antidepressants (TCAs) targets

Answer 47

primary therapeutic benefit is blocking the reuptake of both serotonin and norepinephrine (inhibit NET and SERT)

Question 48

TCAs are antagonists for

Answer 48

5HT2A, 5HT2C, 5HT6, 5HT7 receptors, a1 adrenergic receptor

Question 49

2 Main TCAs

Answer 49

1. imipramine 2. amitriptyline

Question 50

Half-lives of SSRIs

Answer 50

around 24-30 hours, but fluoxetine is 48-96 hours. Active metabolites have half-lives of several days.

Question 51

Discontinuation Syndrome of SSRIs

Answer 51

anxiety, insomnia, headache, nausea. Taper off treatment by reducing dose and then taking on alternating days.

Question 52

Symptoms of Serotonin Syndrome

Answer 52

Agitation or restlessness, hyper-reflexes, diarrhea, fast heart beat and high blood pressure, hallucinations, increased body temperature, loss of coordination, nausea, vomiting - Can be fatal –hyperthermia, tachycardia, lactic acidosis from muscle contraction.

Question 53

Causes of Serotonin Syndrome

Answer 53

TOO MUCH SYNAPTIC SEROTONIN - drug-drug interaction of SSRI + MAOI - SSRIs + dextromethorphan (cough medicine) - SSRIs + triptans (migraine medicines) or some opioids (analgesics) - MDMA

Question 54

Dysthymia

Answer 54

depressed mood lasting longer but less severe than MDD

Question 55

Postpartum depression

Answer 55

caused by sudden drop in estrogen/progesterone

Question 56

Atypical Depression

Answer 56

overeating, oversleeping, ability to react positively to positive events, oversensitivity to rejection

Question 57

Neuropathic Pain

Answer 57

chronic pain & depression co-morbid

Question 58

8 Related Disorders that also respond to antidepressants

Answer 58

1. Dysthymia 2. Postpartum depression 3. Atypical depression 4. Seasonal Affective Disorder 5. Anxiety Disorders 6. OCD 7. Neuropathic Pain 8. Bulimia

Question 59

4 Hallucinogens that are used as rapid antidepressant

Answer 59

1. Ketamine 2. Psilocybin 3. LSD 4. MDMA

Question 60

antagonist of NMDA type of glutamate receptors - increases spine density within 1 hour of treatment. Given intravenously every 1-4 weeks

Answer 60

Ketamine

Question 61

converted to psilocin in the body - agonist of 5HT2A serotonin receptor

Answer 61

Psilocybin

Question 62

agonist of 5HT2A serotonin receptor

Answer 62

LSD (derived from ergot mold)

Question 63

amphetamine like drug that is selective for SERT - reverse transports serotonin

Answer 63

MDMA

Question 64

______act as catalyst for treating depression

Answer 64

Hallucinogens

Question 65

The first antidepressant

Answer 65

Imipramine (first designed as an antipsychotic)

Question 66

neurogenesis

Answer 66

generation of new neurons

Question 67

Most commonly used tricyclic antidepressant

Answer 67

amitriptline