Depression

Question 1

If _______ episodes of depression occur in 5 years or _____ episodes in a lifetime, person needs chronic therapy.

Answer 1

2 or more episodes in 5 years

3 episodes in a lifetime

Question 2

Hypomania

Answer 2

Symptoms of mania for more than 4 days without adverse outcomes

Question 3

Monoamine hypothesis

Answer 3

Depression result of low monoamine levels in neocortex and limbic system
(Antidepressants target monoamine systems - don’t work acutely, require several weeks of administration)

Question 4

HPA dysfunction

Answer 4

Depressed patients have higher than normal cortisol levels in response to higher than normal ACTH levels in response to higher than normal CRF (inc. CRF –> inc. ACTH –> inc. cortisol)

Question 5

Glucocorticoid hypothesis of depression

Answer 5

Glucocorticoid levels high for prolonged period of time, hippocampal neurons damaged and unresponsive (loss of dendrites, decrease in neurogenesis) (hippocampus can’t inhibit hypothalamus, greater glucocorticoid levels, more damage, etc)

Question 6

Neurotrophic Hypothesis

Answer 6

Stress –> decreased BDNF levels –> dendritic atrophy

Neurotropis (helps rebuild dendrites and repair damage - explains delay)

Question 7

TCAs - names

Answer 7

1. Amitriptyline
2. Desipramine
3. Imipramine
4. Nortriptyline
5. Protriptyline
6. Trimipramine

Question 8

TCAs - MOA

Answer 8

Reuptake inhibitors at serotonin or NE receptors (increases concentration of serotonin/NE at synapse)

Question 9

TCAs - CNS Effects

Answer 9

People with depression - elevate mood
Sedation:
2* amine < 3* amines

Question 10

TCAs - ANS effects

Answer 10

Anticholinergic (anti-SLUDGE) (binds muscarinic receptors)
Dirty drugs (not selective)
Some alpha blocking (hypotension)

Question 11

TCAs - CVS effects

Answer 11

Orthostatic hypotension

Arrhythmias (may want to avoid in cardiac patients)

Question 12

Toxicity - TCAs

Answer 12

Two week supply 1500 mg - can be lethal

Question 13

SSRIs - names

Answer 13

1. Fluoxetine (PROZAC)
2. Citalopram (CELEXA)
3. Escitalopram (LEXAPRO)
4. Fluvoxamine ( LUVOX)
5. Sertraline (ZOLOFT)
6. Paroxetine (PAXIL)

Question 14

SSRIs - MOA

Answer 14

Much more selective for blocking serotonin reuptake than TCAs
Lose selectivity at high doses
(No alpha blockade or anti-SLUDGE)

Question 15

SSRIs - adverse effects

Answer 15

Sexual dysfunction 
GI distress (N/V)
      Sertraline - diarrhea
      Paroxetine - constipation
CNS agitation/restlessness (fluoxetine (PROZAC))

Question 16

SSRIs - drug interactions

Answer 16

Serotonin syndrome - can occur when 2 or more serotonergic drugs with different MOA are used together

Fluoxetine and Paroxetine inhibit CYP2D6
2D6 substrates: most TCAs and SSRIs, many antipsychotics, beta blockers

Question 17

Fluoxetine - kinetics/metabolism

Answer 17

N-demethylation

- yields active metabolite (norfluoxetine)

Question 18

Paroxetine extra facts

Answer 18

Withdrawal effects when dc’d (dizziness, tremor, anxiety)

Does not have weight loss effects

Question 19

TCAs vs SSRIs

Answer 19

• efficacy (no significant differences)
• AE (drop out rate SSRIs lower)
• safety (SSRI safer OD, SSRI safer in pregnancy, when DC’d, must taper dose of SSRI that have short half life)