Depression Flashcards
Core symptoms of depression diagnosis
- feeling down, depressed, or hopeless
- loss of interest or pleasure
Other considerations for diagnosis
- Need number of symptoms
- Severity of functional impairment
What is the duration of symptoms required for diagnosis?
2 weeks minimum
Mild depression
Minimum number of symptoms (5+)
Mild functional impairment
Moderate depression
More symptoms and/or more functional impairment
Severe depression
Most symptoms
Marked functional impairment
Treatment for mild depression
Lifestyle changes and counselling
Treatment for moderate depression
Lifestyle changes, counselling, pharmacotherapy, non-drug treatments
What environmental factors can cause depression?
- Stress- early life and on-going (psychological/physical)
- Drugs/alcohol
- Medicines
Pathology of depression
- Uncertain
- Some patients have increase cortisol
- Some patients have structural bairn changes (older)
- Effective drugs suggest deficit in monoamine neurotransmission
Iproniazid
Inhibits monoamine oxidase
Causing euphoria and increased energy
Imipramine
Inhibits reuptake of 5-HT and noradrenaline
Relieving depressive symptoms
What do MAO inhibitor and neurotransmitter reuptake inhibitors essentially do?
Increase post synaptic receptor activity.
What determines synthesis of 5-HT?
TPH/TH
What determines breakdown of 5-HT?
MAO (monoamine oxidase)
What determines the 5-HT vesicular content?
The synthesis and the breakdown. This determines the amount of 5-HT released per action potential.
What determines the release rate of 5-HT?
Firing activity
What determines the reuptake rate of 5-HT?
Transporter activity
What does the release and reuptake rate determine?
The level and duration of 5-HT in synaptic clef and cation of receptor.
MAO inhibitor
Inhibits monoamine oxidase
- Increase neurotransmitter in the vesicle
- Increases neurotransmitter release per impulse
Inhibition of 5-HT reuptake
- Increases duration and concertation of 5-HT/Noradrenaline synaptic cleft
- Increases postsynaptic receptor activation
Reuptake inhibitor drugs
Tricyclics (Non-selective 5-HT/NA)
SSRIs
NARIs
SNRIs
MAO A
Serotonin > Noradrenaline > Dopamine
(Serotonin highest affinity)
MOA B
Dopamine > Noradrenaline > Serotonin
(Dopamine highest affinity)
What are MAO A inhibitors/ MAO A and B inhibitors used for?
Depression treatment
What are MAO B inhibitors used for?
Parkinson’s disease treatment
MAO A inhibitors examples
Clorgyline
Moclobemide
MAO A and B inhibitors examples
Tranylcypromine
Iproniazid
Pargyline
MAO B inhibitors examples
Selegiline
What are problematic interactions with MAO inhibitors?
- ‘Cheese reaction’ – avoid certain foods
- Avoid cold remedies and rec drugs
- Serotonin syndrome – interaction with other ‘serotonergic drugs’
‘Cheese reaction’ and MAO inhibitors
MAO part of cytochrome P450 enzyme, so responsible for breaking down tyramine and other amines.
MOA inhibitors cause amine levels to increase.
-Increases BP (alpha-1 vasoconstriction)
-Provoke hypertensive crisis
Irreversible blockade of enzymes through MAO inhibitors.
MAOI can bind to enzyme irreversible, so effects outlast clearance of the drug (drug not present in plasma levels).
New enzymes required to synthesis (6 weeks)
2 TAC examples
Amitriptyline
Desipramine
What differs in reuptake inhibitors? (3)
- 5-HT/NA selectivity
- Other pharmacology
- Half-life
2 SSRI examples
Citalopram
Paroxetine
2 SNRI examples
Duloxetine
Venlafaxine
5-HT/NA selectivity of reuptake inhibitors
The relative potency of the 5-HT and NA transporters for different drugs varies
TAC- small difference
SSRIs- big difference
SNRIs- small difference
How are TACs non-selective and ‘dirty’?
Small difference. Because at the doses taken they attach to other receptors (e.g. H1, NA alpha 1 and mACh)
How are SSRIs selective and ‘clean’?
Big gap for affinity for 5-HT transporter and affinity for other receptors. So at the doses taken not going to be blocking other unwanted receptors.
How are SNRIs non-selective and ‘clean’?
Small gap but do not have affinity for other unwanted receptors.
What is blocking of histamine H1 receptor associated with? (side effects)
Sedation (sleepy and weight gain)
What is blocking of 5-HT transporter associated with? (side effects)
Sexual defunction and GI disturbances
What is blocking of NA alpha 1 receptor associated with? (side effects)
Postural hypotension
What is blocking of mACh (muscarinic acetylcholine receptor associated with? (side effects)
Dry mouth, urinary retention, and constipation
What is blocking of NA transporter associated with? (side effects)
Anxiety
First line drug treatment for depression
SSRI- sertraline, citalopram
-Low dose and titrate up
Lifestyle changes for depression
- Dec drug/alcohol
- Dec stress
- Inc social and physical activity
Poor response to treatment: Dose
Titrate while tolerable
Poor response to treatment: Antidepressant type
Switch antidepressant
Poor response to treatment: Additional drugs
Different antidepressant, antipsychotic, lithium
Poor response to treatment: Non-drug therapy
CBT
Why is SSRI first line?
Well tolerated and few side effects
TCAs effectiveness and side effects
More side effects (but sedation may be useful for insomnia)
More dangerous in overdose
SNRIs effectiveness and side effects
More efficacious in treatment for depression, but less well tolerated
MAOIs effectiveness and side effects
Effective but difficult to take
What SSRI has a long half-life?
Fluoxetine, so couple weeks to clear out
Discontinuation of antidepressants management
Switch to fluoxetine due to long half life. Reduce dose slowly.
Treat symptoms
Discontinuation of antidepressants withdrawal
Flu-like symptoms Nausea Anxiety ‘Electric shocks’ Difficulty sleeping
What SSRI has a short half-life?
Paroxetine (Seroxat)/venlafaxine
