Depression Flashcards
Which antidepressants are more effective in treating negative activity?
5-HT antidepressants
Which antidepressants are more effective in treating positive symptoms?
Dopaminergic and noradrenergic antidepressants
Explain the monoamine theory?
Depressive disorders are caused by a functional deficit of monoamine neurotransmitters
Evidence: More 5-HT/NA, increase mood, Less 5-HT/NA, lower mood
What are some symptoms of disruptive mood dysregulation disorder?
- Severe recurrent temper outbursts manifested verbally or behaviourally that are grossly out of proportion to the situation
- Temper outburst inconsistent with developmental level
- Temper outburst occur ≥ 3 times a week
Symptoms have to be present for ≥ 12 months and in more than 2-3 different settings. Usually 6-18 years old
Symptoms of Major depressive disorder?
At least 5 of the following during a 2 week period:
- Depressed mood most of the day
- Markedly diminished interest of pleasure in almost all activities
- Weight loss
- Insomnia or hypersomnia
- Psychomotor agitation or retardation
- Fatigue/ loss of energy
- Feelings of worthlessness or excessive/ inappropriate guilt
- Diminished ability to think or concentrate
- Recurrent thoughts of death
How is persistent depressive disorder classified?
Depressed mood for most of the day for >2 years
Signs of : poor appetite, insomnia or hypersomnia, low energy or fatigue, lost self esteem, poor concentration
Symptoms are less severe but longer lasting than MDD
3 treatments for depressive disorders?
- psychotherapy
- Electroconvulsive therapy
- Pharmacotherapy
What are some examples of psychotherapy?
- Cognitive behavioural therapy
- Mindfulness- based stress reduction
- Meditation
- Yoga
What is ECT?
Electroconvulsive therapy
- Mild electric shock to each side of the patients skull near the temples for ~ 1 min
- Causes a brief seizure within brain
When is ECT useful?
When the depressive disorder is severe or life threatening
People who cannot or prefer not to take antidepressants (eg: pregnancy)
4 mechanisms of action of antidepressants?
- Uptake inhibition- NA, 5-HT, DA
- Receptor antagonism
- Enzyme inhibition- MAO
- Receptor agonism- melatonin receptor agoinist
How long does it take to see therapeutic effects of antidepressants?
up to 6 weeks
Symptoms start to resolve in 2-4 weeks ad full resolution of symptoms may take up to 4 months
What does chronic antidepressant treatment result in?
Secondary adaptive changes
- Downregulation of b1, b2 and 5-HT2a+c receptors
- Alterations in kinases, transcription factors, growth factors
What are some types of SSRIs?
Sertraline Fluoxetine Paroxetine Citalopram Escitaloptam Fluvoxamine
How do SSRIs increase 5-HT in the long term?
Continued administration results in a downregulation of 5-HT1a receptors on cell body in the raphe which ‘releases the brake’ to release more 5-HT
What are some adverse effects of SSRIs?
- Nausea
- Somnolence/ insomnia
- Dry mouth
- Increased sweating
- Diarrhoea
- Ejaculatory disorder
- Serotonin syndrome
SNRIs have similar adverse effects
What is the mechanism of action of TCAs?
Main effect- blocks the reuptake of NA and 5-HT, some DA reuptake block
Blocks other receptors: a1, a2, M, H (a2 block results a negative feedback and increase NA release, this contributes to therapeutic effect as well)
What are some initial side effects of TCAs? (3)
- Sedation
- Confusion
- Motor incoordination
These will usually decrease in 1-2 weeks
What are some chronic side effects of TCAs? (4)
- Atropinic side effects: dry mouth, blurred vision, tachycardia
- Postural hypotension
- Can affect cognitive function
- Prolongation of QT interval
Is it possible to overdose with TCAs?
Yes, active metabolites.
Can lead to Arrhythmia, convulsion, respiratory depression, coma and death
What are 2 functions of MAO?
- Inactivates amines eg: 5-HT, NA and tyramine
- Regulates levels of NA and 5-HT in neurones
Found on the outer membrane of mitochrondria
What is an example of a reversible MAO-A inhibitor?
Moclobemide.
It blocks MAO-A which causes a leakage of neurotransmitters from neurones
irreversible MAOI- phenelzine/ tranylcypromine
What are some side effects of moclobemide? (5)
- Insomnia
- Dizziness
- Dry mouth
- Nausea
- GI effects
- Cheese reaction
What is the ‘cheese reaction’?
A hypertensive crisis
Tyramine which is commonly found in cheese, red wine, vegemite is normally metabolised in gut wall
When it is not metabolised, it can a amphetamine like effect and displaces NA from vesicles
Irreversible MOAI can also increase NA, thus causing acute hypertension
Therefore need to restrict dietary intake of tyramine
