Depression

Question 1

Signs and symptoms of depression

Answer 1

Psychological - pessimism, poor concentration, lack of motivation
Biological - fatigue, loss of appetite, sleep disturbance
Behavioural - psychomotor agitation/retardation, self-neglect

Question 2

Two types of depression

Answer 2

Unipolar - 75% due to stressful life events, 25% familial
Bipolar - Depression/mania alternating lasting 2 weeks mood change and 1 week mania (BP-1 mania, BP-2 hypomania), strong hereditary tendency

Question 3

What are thymoleptics

Answer 3

Drugs which re-elevate mood e.g. monoamine reuptake inhibitors

Question 4

What are thymeretics

Answer 4

Drugs that activate psychomotor drive e.g. MAOIs

Question 5

Classes of antidepressant treatments

Answer 5

MAOIs
Reuptake inhibitors (TCAs, SSRIs, NRIs, SNRIs)
Mix of two above
Intracellular messenger targeted (PDE inhibitor (rolipram))
Electroconvulsive therapy

Question 6

MAO-A inhibitors

Answer 6

Inhibits MAO-A in nerve terminal, efflux of nt via reuptake transporter (which is reversed), works well for depression with anxiety/hypochondria/phobia

Question 7

Irreversible non-selective MAOIs

Answer 7

Phenelzine

Tranylcypromine

Question 8

Reversible MAO-A inhibitor

Answer 8

Moclobemide

Question 9

MAO-A inhibitor SE

Answer 9

Cheese reaction - MAO-A metabolises dietary tyrosine prevents it displacing NA in symptoms nerve endings so has sympathetic effects
Postural hypotension
Fatal respiratory depression with alcohol/barbiturates

Question 10

Monoamine reuptake inhibitors

Answer 10

TCAs - imipramine, clomipramine, amitriptyline prefer SERT, desipramine prefers NET
SSRIs - Zimelidine, fluoxetine, citalopram (most SERT selective), paroxetine (most potent), vortioxetine, fluvoxamine, sertraline
SNRIs - Venlaxafine
NRIs - Maprotiline

Question 11

TCA MOA

Answer 11

Imipramine/clomipramine/amitriptyline/despiramine inhibit 5HT + NA reuptake

Question 12

TCA SE (due to alpha-1, H1, mACh action)

Answer 12

Takes 2-3 weeks so develop, acutely sedation, confusion
Postural hypotension
Sedation
Dry mouth, blurred vision, constipation etc
Acute cardiotoxicity
OD/ Drug interactions with depressants etc

Question 13

SSRI SE

Answer 13

GI issues
Rash/tremor/urticaria (hives)
Loss of libido
Interacts with MAO inhibitors but safer in OD

Question 14

Venlaxafine transporter preference

Answer 14

Low dose SERT, high dose =

Question 15

Mirtazapine + mianserin MOA

Answer 15

Tetracyclic like maprotiline so acts as NRI, also alpha-2 antagonist so presynaptic feedback inhibition of NA/5HT blocked
Also 5HT2A/5HT3 antagonist, decreases non-selective serotonergic SE

Question 16

Trazodone MOA

Answer 16

SARI - serotonin antagonist and reuptake inhibitor (5HT2 antagonist which is expressed highly in depression)

Question 17

Atypical antidepressants which don’t affect monoamines

Answer 17

Iprindole (not really used)

Question 18

Lithium MOA

Answer 18

Decreases GPCR (Gs) activity, slows down oscillation of moods

Question 19

Lithium problems

Answer 19

Toxic over 2mM

Question 20

Ketamine (not used currently) MOA

Answer 20

Blocks NMDA
enhances AMPA activation
disinhibits glutamate release
activates protein translation and BDNF pathway