1. Jonathan Tsun & Ilona Blee
Depression
Jonathan Tsun & Ilona Blee

2. Depression Symptoms 5 characteristic symptoms (ICD-10) Depressed mood
Loss of interest and enjoyment
Reduced energy
Increased fatiguability
Diminished activity
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3. Depression Symptoms List some more common symptoms?
Reduced concentration and attention
Reduced self-esteem and self-confidence
Ideas of guilt and unworthiness
Bleak and pessimistic views of the future
Ideas or acts of self-harm or suicide
Disturbed sleep
Diminished appetite
Anxiety and distress
Motor agitation or slowing of movements
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4. 3 Types Mild depression Moderate depression Severe depression
At least two of: Depressed mood; loss of interest and enjoyment; increased fatiguability
PLUS at least two more of the other symptoms
Minor functional impairment
Episode lasts at least 2 weeks
Moderate depression
At least two of: Depressed mood; loss of interest and enjoyment; increased fatiguability
PLUS at least three to four of the other symptoms
Considerable difficulty continuing with social, work, domestic activities
Episode lasts at least 2 weeks
Severe depression
All three of: Depressed mood; loss of interest and enjoyment; increased fatiguability
PLUS at least four of the other symptoms
Unlikely able to continue with social, work, or domestic activities (significant functional impairment)
Episode may last less than 2 weeks if symptoms are severe enough
**Can occur with or without psychotic symptoms
NOTE: You can only classify single episodes of depression as mild-severe.

5. 2 Patterns Unipolar Bipolar Dysthymia – low mood
Melancholia – major depression
Atypical depression
Bipolar
Bipolar disorder
Cyclothymia
This came up in an SAQ!

6. Physiology of depression…
A bunch of guesswork, really…

7. Brain structures involved…
Mood stability depends on the balance between reward and stress circuits of the brain

8. Which areas of the brain show decreased activity?
Prefrontal cortex
Deficits lead to problems with concentration, motivation, problem solving ability
Hippocampus
Deficits lead to memory problems
Which areas of the brain show increased activity?
Amygdala
Fear conditioning centre of the brain
Hypothalamus
Start of the stress axis (HPA axis)
Prefrontal cortex – responsible for planning complex cognitive behaviour, decision making, moderating social behaviour
Hippocampus – responsible for learning, memory consolidation, spatial recognition

9. Theories for Depression
Neurotransmitter imbalance
Serotonin insufficiency
Noradrenaline insufficiency
Neurohormone imbalance
Steroids
HPA axis
Immune
Inflammatory response  stimulate HPA axis
Circadian
Changes in circadian rhythms  Seasonal Affective Disorder
Neurogenic
Decreased spreading of dendrites (arborisation)
Decreased synapses
Neurotransmitter overproduction
The bullet point highlighted in red is the main focus for depression theories because serotonin and noradrenaline are the main targets for pharmacological intervention

10. Selective Serotonin Reuptake Inhibitors
MoA:
Inhibit 5HT reuptake into pre-synaptic cell
Allows elevated levels of 5HT to remain in the synaptic cleft and bind with post-synaptic cell
Side-effects:
Slow onset
Nausea
Sexual dysfunction
Serotonin syndrome – excess serotonin (over-activation of ANS)
Examples:
Fluoxetine (Prozac)
Citalopram
Paroxetine
As mentioned during the presentation, try to think about how the question might be asked during the exam
For example if they asked for the mechanism of action of an SSRI for two marks, make sure you mention key words in your answer like serotonin reuptake is inhibited and this therefore leads to an increased level in the synaptic cleft.
Listing side effects can be an exam question for a couple of marks

11. Tricyclic Antidepressants
MoA:
5HT reuptake blocker
NA reuptake blocker
α1 adrenoreceptor antagonist
H1 receptor antagonist
M1 receptor antagonist
Side-effects:
Sedation – H1 receptor antagonist
Dry mouth, eyes – M1 receptor antagonist
Orthostatic hypotension – α1 adrenoreceptor antagonist
Examples:
Amitriptyline
Nortriptyline
Cocaine
The side effects of tricyclic antidepressants came up in our SAQ exam
So the question was a patient taking amityriptyline, why are they getting dry mouth and eyes and feeling sedated
So you would have to explain that they are feeling sedated because part of the mechanism of action of tricyclic antidepressants is to block H1 histamine receptors, and they are having dry eyes and mouth because of the M1 muscarinic receptors are being blocked. You must specify the fact the number in the receptor as 1 otherwise you aren’t explaining the side effect.

12. Monoamine oxidase inhibitors (A)
What is their mechanism of action?
Block breakdown of 5HT and NA by inhibiting enzymatic breakdown
This will increase 5HT/NA levels at the synapse
Name TWO examples of a monoamine oxidase inhibitor (A).
Phenelzine
Moclobemide

13. Why are monoamine oxidase inhibitors (A) or MAOIs memorable?
The only antidepressant drug to have the ‘cheese reaction’ as a side effect
What is the ‘cheese reaction’? (I’ve broken it down into 4 basic steps)
Reaction to food containing tyramine
Normally this is broken down by monoamine oxidase
If left not broken down it can circulate in the body and be taken up by adrenergic neurons and cause the release of noradrenaline
This causes effects like hypertension, tachycardia and arrhythmias
List two other side effects of monoamine oxidase inhibitors (A).
Postural hypotension
Sleep disorders
Also note you CANNOT use these drugs with SSRIs/TCAs. This is a drug that has a lot of cross reactions and you have to inform the patient of not being able to eat foods like cheese or wine, anything containing tyramine.

14. Atypical antidepressants
Name TWO examples of an atypical antidepressant
Reboxetine
Venlafaxine
Buspirone
Reboxetine is a NaRI. What is its mechanism of action?
Same as SSRIs
What is the mechanism of action of buspirone?
5HT partial agonists reduce activity to increase transmitter levels – act on pre-synaptic terminals. Reduction of activity reduces extra growths which were being used to mop up excess neurotransmitter

15. Cognitive Behavioural Therapy

16. What conditions can CBT be beneficial for?
Depression
Anxiety and panic attacks
Addictions (e.g. pathological gambling)
Obsessive-compulsive disorder
Drug or alcohol problems
Eating disorders
Phobias
Chronic fatigue syndrome

17. What are the four aims of CBT?
Identify thinking that causes problematic feelings & behaviours
Question the individual’s negative thinking
Identify unwanted behaviour patterns
Plan behavioural goals and steps to achieve goals
This came up as an SAQ! And it was a mark for each of these four aims, and very specific about the wording of the answer.

18. CBT Techniques Challenging irrational beliefs
Reframing/replacing them with alternative, rational thoughts
Thought stopping
Graded exposure
Assertiveness
Social Skills training
Problem solving training
Relaxation techniques
The may ask you to list different CBT techniques in a similar sort of way for a SAQ
Similarly they might describe a CBT technique in the stem and then have 5 of these listed and you would have to pick the correct one being described as an MCQ

19. Which of the following drugs is NOT active as an antidepressant agent?
Amitriptyline
Fluoxetine
Moclobemide
Buspirone
Lithium
None of the above
Answer: these are ALL active as antidepressant drugs. However for MCQ’s they might give a list of very similar sounding drugs for different aspects of brain and behaviour and your would have to pick one that you know is used to treat depression or pick the one that is a selective serotonin reuptake inhibitor for example

20. Which of the following is NOT a known action of the antidepressant agents?
Inhibition of monoamine neurotransmitter re-uptake
Block of amine deamination of monoamine neurotransmitter
Activation of dopamine D2 receptors
Antagonist of alpha-adrenoceptors
Increasing 5HT levels by inhibiting re-uptake pump
Answer is C. Activation of D2 receptors as this isn’t a mechanism of action of any of the drugs we have learnt about to treat depression. Typical antipsychotics actually do the opposite and BLOCK D2 receptors in the extrapyramidal system.

21. The “cheese reaction” is a known side effect of which class of antidepressant?
Selective serotonin reuptake inhibitors
Tricyclic antidepressants
Monoamine (A) oxidase inhibitors
Atypical antidepressants
Lithium
Answer: C. monoamine A oxidase inhibitors

22. Thank you!
Any questions?