Depression

Question 1

What is bipolar depression?

Answer 1

Oscillations between depression and mania).
Affect 0.6 million.
Begins in early life.
Strong familial links.
Treatment: ECT or lithium

Question 2

What is SAD?

Answer 2

Seasonal affective disorder.
0.5 million.
Linked to circadian genes?
Occurs in winter - and arctic altitudes.
Treatment: light therapy.

Question 3

What is unipolar depression

Answer 3

6 million
Affects females more than males.
Reactive or familial? (75:25)
Sert polymorphism?
Treatment: drugs, ECT, psychotherapy.

Question 4

What clinically defines depression?

Answer 4

5 or more of the symptoms present for the same 2 week period and represent a change from previous functioning

1) Mood (depressed)
2) Decreased pleasure
3) Change of 5% weight
4) Sleep - insomnia or hypersomnia
5) Psychomotor - agitation/retardation
6) Energy levels - fatigue
7) Lack of self worth
8) Concentration
9) Suicide (thoughts, plans, attempts)

Question 5

Explain ECT.

Answer 5

Electroconvulsive therapy (severe/not responding to drugs).
Suxamethonium for NM block
unilateral electric shock - causes a seizure.

Question 6

Explain Psychological treatments.

Answer 6

Mild to moderate depression.

Psycotherapy/ cognitive behaviour therapy.

Question 7

What is the monoamine hypothesis of depression?

Answer 7

Depression is caused by a functional deficit of MA transmitters in certain areas of the brain.

Question 8

Support for the MA hypothesis?

Answer 8

Many drugs that increase the functional availability of MAs, decrease depression (TCA, MAOI)
Drugs that decrease MA cause depression like symptoms.
Drugs that decrease NA synthesis = depression like behaviour (a-methyl tyrosine, methyldopa)

Question 9

Evidence against hypothesis?

Answer 9

Theraputic lag - 8-12 weeks for symptomatic improvement…(drugs increase MA in brain immeadiately but for synaptic remodelling, change in receptor number = weeks).
ECT and psychology dont alter MA levels.
Cocaine and amphetamines increase NAdr availablity but aren’t antidepressants
L-dopa - no effect

Question 10

Which MAs are reduced?

Answer 10

NA (locus coeruleus and naudal raphe nucleus)
5HT: caudal and rostral raphe nucleus.
Maybe dopamine too?!

Question 11

Give a list of the drugs used to treat depression…

Answer 11

MAOIs: phenelzine, moclobemide
TCAs: imipramine, clomipramine
SSRI: fluoxetine
NSRI: reboxitine
SNRI: venlafaxine
Atypicals: mirtazapine.

Question 12

How do MAOIs work?

Answer 12

Phenelzine, moclobemide
Inhibit the breakdown of MAs…
Increase NA and 5HT levels.

2-4 weeks for effect.

Question 13

Complications of MAOIs?

Answer 13

Cheese reaction…normallyh tyramine is broken down by MAOs in gut…but if MAOA and B are inhibited by phenelzine then tyramine enters system circulation and is taken up by NAddr tranporters, diplaces and releases NAdr. Increase BP severely!

Solution: MAOa selective…moclobemide (reversible)

Question 14

How do TCAs work?

Answer 14

Imipramine, Clomipramine.
Inhibit NA and 5HT transporters.
2-4 weeks for antidepressant effect.
Antagonists at other receptors (musc, H1 and alpha1) therefore side effects - sedation, postural hypotension, insomnia etc.

OVERDOSE - potentially fatal cardia arrythmia…block use dependant sodium channels.

Question 15

How do SSRIs work?

Answer 15

Seretonin Selective Reuptake inhibitors.
Inhibit 5HT reuptake.
Fluoxetine (prozac)
Less SE than TCA - overdose not fatal…nausea, sexual dysfunction, weight gain, personality changes.

Question 16

NSRIs - how do they work?

Answer 16

Inhibit noradrenaline reuptake.
2-4 weeks
Reboxetine
insomnia.

Question 17

SNRIs?

Answer 17

Inhibit both 5HT and NAdr reuptake.

Venlafaxine.

Question 18

Atypicals?

Answer 18

Block NA/5HT presynaptic receptors.
Mirtazapine.
Weight gain.

Question 19

Name some future antidepressants.

Answer 19

Triple uptake inhibitors.
NK1 antagonist.
Glutamate receptor antagonists.
Nicotinic AChR antagonist.
Antiglucocorticoids.
Agomelatine : melatonin receptor antag.