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Depression - Coggle Diagram
Depression
Drug selection
Based on safety in OD, ADRs profile, comorbidities, age, withdrawl symptoms, and DDIs
Least toxic:
SSRIs, mirtazapine, reboxetine and moclobemide
(Citalopram and Escitalopram associated with QT prolongation)
Mid:
Velafaxine
(Risk of seizures in +5g OD and cardiotoxicity at +8g OD)
Most toxic:
TCAs and MAOIs
(high risk of OD for suicide at 10+mg/kg)
Treatment
First Line:
SSRIs (citalopram, escitalopram, fluoxitine, fluvoxamine, paroxitine and sertaline) TCA: Mirtazapine
Well tolerated and safe, around 1 week to reach steady state.
Mirtazapine has a wide safety margin
Second line:
SNRIs (desvenlafaxine, venlafaxine and duloxitine) Others: agomelatine and vorioxetine
Similar safety and efficacy to SSRIs.
Third line:
moclobemide and reboxitine due to limited evidence to use as first line.
Around 8 weeks for maximum effect and another 6-12 months for remission.
For high risk/very severe cases: 2-3+ years of treatment before consider stopping
ADRs and Risks
First line agents
Paroxitine
: more weight gain
All SSRIs:
GI effects and sexual dysfunction
Mirtazapine
: mass weight gain and sedation (good for insomnia and thin patients.)
Second line agents
Similar profile to SSRIs
Venlafaxine
: can cause significant increase in BP
Third line agents
Safety in toxicity are limited. Both moclobemide and reboxitine can cause insomnia
Reboxitine: potential urinary hesitancy in older males, reduction in potassium and sodium in plasma. Metabolised by 3A4 thus potential DDIs.
Bleeding:
SSRIs blocks uptake of serotonin into platelets causing increase risk of GI bleeds. For high risk patients, consider different class of antidepressant and use PPI for gastroprotective.
Hyponatraemia:
caused by TCAs, SSRIs, SNRIs and MAOIs. Signs include nausea and malaise and in severe cases, convulsions, coma and death. High risk include older age, female, low BW, polypharmacy and impaired renal function.
SSRIs and DDIs:
Citalopram, escitalopram and sertaline
are the less interactive drugs (newer)
Switching drugs
Drug free period table to prevent serotonin syndrome and rebound of depression
Some drugs have longer half life thus washout period is longer
4 methods of switching
Conservative switching: taper 1st antidepressant and stop, washout period then initate new drug at recommended levels.
Moderate switch: taper 1st drug, and stopped, wash out for 2-4 weeks and start new drug at lowest drug
Direct switch: Stopped 1st drug and start new drug on next day
Cross taper switch: taper 1st drug slowly and stop while gradually increasing new drug starting at lowest dose.
Treatment resistance
Defined as persist state despite effect dose usage of 2 drugs.
Add on
lithium:
increases serontonin response, second gen antipsychotic (
Quetiapine and Aripiprazole
): serotonin agonist properties and
tri-iodothyronine
(T3).
Irreversible non-selective MAOI:
Phenelzine
(specialist only due to high risk of serotonin syndrome)
Mianserin
: less ADRs (CV and ACh ADRs) than TCAs and safer OD profile.
Last line: TCAs
: Nortripyline is used due to lower ACh ADRs.
Discontinuing treatment
Tapered slowly to reduce risk of discontinuation syndrome (N/V, insomnia, postual imbalance, and flu-like symptoms).
Withdrawal effects (TCAs): cholinergic rebound: hypersalivation, runny nose, diarrhoea.
(SSRIs): nausea, anxiety, agitation, tremor, sweating confusion.
Treatment with pregnancy
Antidepressants in pregnancy are generally safe and minimal exposure of drug to the fetus and via breastmilk (except fluoxetine)