Pharmacology Flashcards
antidepressant prescribing
Start SSRI and assess efficacy after 2 weeks
- increase dose if no improvement after weeks 3-4
- consider switching to another SSRI if no improvement after week 6
If no response after 2 SSRIs = switch to another class e.g. NASSA, SNRI
If no response after 3 antidepressants, then consider treatment choices for refractory depression
Treatment resistant depression
Options:
- combining antidepressants (e.g. mirtazapine + venlafaxine aka California Rocket Fuel)
- augmentation with a mood stabiliser (lithium or lamotrigine) or an antipsychotic
- ketamine/esketamine
- ECT
- transcranial magnetic stimulation
- Adding thyroxine/T3 (rarely used)
Antidepressant Classes
SSRIs = citalopram, escitalopram, sertraline, fluoxetine, paroxetine
SNRIs = venlafaxine, duloxetine
NASSA = mirtazapine
SARIs = trazado
MAOI = phenelzine, tranylcypromaine, moclobemide, isocarboxacid (rarely all used)
TCAs = clomipramine, imipramine, amitryptuline,
Serotonin synthesis
Serotonin release and inactivation
SSRIs
Citalopram, escitalopram, sertraline, fluoxetine, paroxetine
Upon activation, 5-HT1A receptors inhibit firing of 5-HT neurone
SNRIS
Venlafaxine and Duloxetine
NASSA
Mirtazapine
- a2 receptor antagonist and H1 blocker → sedation and increased appetite (helpful for poor sleep but can lead to weight gain)
TCAs
Amitryptaline, clomipramine
H1 (sedation, weight gain)
M1 (dry mouth, blurred vision, urinary retention, constipation)
A1 (hypotension, dizziness)
VGSC blockage (coma, seizures, heart arrhythmias when used in overdose)
risk in overdose means 2nd line agent
ECG changes = PR, QRS, QT interval prolongation, nonspecific ST segment and T wave changes AV block, RA deviation
The Cheese Reaction
aka dietary tyramine interaction
pts taking a MAOI and consuming tyramine in diet are at risk of developing HYPERTENSIVE CRISIS
Serotonin syndrome aka serotonin toxicity
Life threatening
high risk = in high dose/multiple antidepressants, MAOIs/TCAs, tramadol (opiate) as has serotonergic activity
clinical diagnosis, no tests are available
‘Melting snowman’
- mild = insomnia, anxiety, nausea, diarrhoea, HTN, hyper-reflexia
- moderate = agitation, myoclonus, tremor, mydriasis, diaphoresis, low grade fever
- severe = hyperthermia, confusion, rigidity, respiratory failure, coma, death
take home sx = altered mental status, sweating, fever, hyper-reflexia/clonus
mx = stop antidepressants, fluids and supportive care
Stopping antidepressants
avoid withdrawal syndrome (especially from venlafaxine and paroxetine)
long half-life less likely withdrawal e.g. fluoxetine
sx (mild ‘flu-like’) and lasts for 1-2 weeks) = restlessness, sweating, electric shock sensations in scalp, insomnia, GI upset
mx = taper over 2-4 weeks to avoid withdrawal, cross-taper (reduce one, increase the other during switching)
St John’s Wort (hypericum perforatum)
can be bought OTC with reported beneficial effects on mood
efficacy on depression is unclear, should not be recommended
increased risk of bleeding
potent hepatic enzyme inducer
Debunking antidepressant myths
2-6 weeks for them to work
they are not addictive, but there can be dependency
tx length depends on nature of illness and risk
- rule of thumb = continue for 6-9 months following resolution of the episode of illness
review regularly (i.e. weekly) when starting antidepressants in the young due to the theoretical risk of suicidality
antidepressants can precipitate hypomanic episodes in those with an underlying bipolar illness = 1st line tx for bipolar depression is mood stabilisers, not antidepressants
