Depression Flashcards
define depression
clinical disorder characterized by persistent low mood, loss of interest/enjoyment, neuro-vegetative disturbance and lack of energy causing social and occupational dysfunction
symptoms of depression
core symptoms - persistent low mood, anhedonia, anergia
physical symptoms - pain, lack of concentration, self harm, sleep and appetite disturbance
Aetiology of depression
Monoamine deficiency hypothesis
- depression is due to deficiency in 1 of 3 biogenic amines - serotonin, noradrenaline, dopamine
moa of antidepressants
they increase serotonin/noradrenaline NTs presynaptically by preventing breakdown of NT (MAO) or preventing reuptake of NT by synaptic cleft
how long do antidepressants take to work
antidepressants show effects from weeks 1-2
full response is gradual, takes several weeks and months
what are the diagnoses?
based on DSM-4
symptoms:
depressed mood
weight loss/reduced appetite
insomnia
recurrent thoughts of death/suicide
lack of energy
agitation
reduced interest/pleasure
reduced ability to concentrate
major depressive disorder - presence of at least 5 symptoms
sub-threshold (minor) depression - presence of 2-4 symptoms, > 2 weeks
persistent depressive disorder (dysthymic disorder) - characterised by 3 dysthymic symptoms for at least 2 years
self reporting screening for depression diagnosis:
- patient health questionnaire 9 (PHQ9)
- beck depression inventory (BDI)
what antidepressant groups are there?
SSRI - selective serotonin reuptake inhibitors - fluoxetine, paroxetine, sertraline, citalopram
TCA - tricyclic antidepressants - amitriptyline, clomipramine, doxepin
SNRI - serotonin and noradrenaline reuptake inhibitors - venlafaxine, duloxetine
MAOI - monoamine oxidase inhibitors - phenelzine, tranylcypromine, selegiline
others - mirtazapine
what to do if minimal response to antidepressant after 3/4 weeks
increase level of support, increase weekly phone calls,
consider switching in or b/w classes of antidepressants - although little benefit shown
consider switching to diff SSRI or better tolerated newer generation
consider augmentation - antidepressant + non antidepressant
combination - 2 antidepressants
MoA + imp points of SSRIs
SSRIs selectively inhibit serotonin transport - block reuptake of serotonin at synapses - this increases serotonin at serotonergic neurones
have less S.Es than TCAs - so first line
SSRIs differ in affinity to block 5-HT transporters
- paroxetine - most affinity, no active metabolite
- citalopram - most selective, desmethyl metabolite
cannot stop SSRIs abruptly or change SSRI to MOAI - can lead to serotonin syndrome
- leads to tremor, hypertension, hyperthermia
- dose should be tapered down allow a 2-week washout period
common adverse effects - nausea, vomiting, dyspepsia, sexual dysfunction
MOA of SNRI
combined blockade of 5HT/noradrenaline like TCAs but less side effects
pharmacological effect of venlafaxine is dose dependent
- low dose - acts like SSRI
- medium to high dose - additional NA reuptake inhibition
- high dose - additional dopamine reuptake inhibition
moa of TCAs
serotonin and noradrenaline reuptake inhibition by competing for carrier transport system
degree and selectivity of inhibition for 5HT vs NA differs across family of TCAs
- clomipramine - most potent at 5HT pump
- desipramine most potent at NA reuptake pump
TCAs - atropine like effects and postural hypotension
- TCAs and MAOi shouldn’t be used together
moa of MAOIs
increase availability of monoamine NTs - serotonin, dopamine and noradrenaline by decreasing their metabolism
classical MAOIs were non-selective and irreversible (tranylcypromine)
newer ones are selective for MAO-A and MAO-B and reversible for MAO-A
MAO - enzyme for metabolism of serotonin, dopamine, noradrenaline
MAO-A - metabolises 5HT, NA, DA
MAO-B - mainly metabolises DA
S.E - atropine like effects, postural hypotension, weight gain, CNS stimulation - restlessness, tremor, insomnia
MOA and points about mirtazapine
alpha 2 adrenergic receptor antagonist so disinhibits serotonin and NA neurotransmission
highly sedating at low doses - so give before sleep
selective for noradrenergic and dopaminergic systems
