Depression Flashcards
What causes depression and how antidepressants help ?
depression is caused by under activity of monoamine neurotransmitters. Antidepressants increase monoamine levels at synapse
Name Tricyclic antidepressants ?
Amitriptyline Clomipramine Dosulepin Doxepin Imipramine ( most antimuscarinic TCA ) Lofepramine ( hepatoxicity ) Nortriptyline Trimipramine
Name tricyclic related antidepressants ?
Mianserin
Trazadone
Name irreversible monoamine oxidase inhibitors ?
phenelzine ( hepatoxicity more likely )
isocarboxazid ( hepatoxcity more likely )
Tranylcypromine ( hypertensive crises more likely )
Name reversible monoamine oxidase inhibitors ?
moclobemide ( no washout period needed: short acting )
Name SSRIs ?
citalopram ( qt prolongation )
escitalopram ( qt prolongation )
fluoxetine ( only antidepressants licensed in children )
fluvoxamine
paroxetine ( greater risk of withdrawal reactions )
sertraline ( safer to use after MI, unstable angina )
What are other antidepressant drugs ?
agomelatine ( hepatoxicity; give treatment booklet )
duloxetine ( SNRI )
flupentixol
mirtazepine ( blood dyscrasias )
reboxetine (NRI)
Tryptophan
Venlafaxine ( SNRI; higher risk of withdrawal reaction )
Vortioxetine ( works on serotonergic pathway )
Why SSRIs are first line treatment for depression and not TCA’s ?
less sedating, less antimuscarinic, less epileptogenic, less cardiotoxic. Also safest in overdose
When antidepressants are initiated how long does it usually take to work and how often patients should be reviewed at the start of their treatment ?
Takes at least two weeks to work : initially feels worse, increased agitation, anxiety and suicidal ideation.
Review every one to two weeks
How long should GP’s wait before deeming SSRIs ineffective ?
Wait at least 4 weeks ( 6 weeks in elderly )
How long SSRIs should be taken for ?
Continue for at least 6 months ( 12 months in elderly )
12 months in generalised anxiety disorder ( high risk of relapse )
2 years in recurrent depression
What is a second line treatment in depression ?
Increase SSRI dose, change to different SSRI or mirtazapine
Other choices: lofepramine ( TCA ) reboxetine, moclobemide
What is a third line treatment for depression ?
add another antidepressant class or augmenting agent : lithium or antipsychotic. Electroconvulsive therapy in severe refractory depression.
Antidepressants side effects ?
- Hyponatraemia ( drowsiness, confusion, convulsion) = especially SSRIs and in the elderly
- Suicidal ideation and behaviour ( at risk are young children and adults ) = important to monitor for signs of this after dose change and at the start of the treatment
- serotonin syndrome
What are the signs and symptoms of serotonin syndrome ?
- Neuromascular hyperactivity : tremors, myoclonus, muscle rigidity
- Altered mental state : agitation, confusion, mania
- Autonomic dysfunction: labile blood pressure, urination, diarrhoea, hyperthermia, tachycardia, pallor, sweating, shivering
Why is washout period required when switching antidepressants ?
to prevent serotonin syndrome
How long is washout period for the following antidepressants :
MAOIs
SSRIs
TCAs
MAOIs wait two weeks before switching ( moclobemide does not require a washout period )
SSRIs wait one week before switching ( two weeks if sertraline, 5 weeks if fluoxetine )
TCAs wait one to two weeks before switching ( three weeks if imipramine or clomipramine )
When usually withdrawal effects occur ?
within five days of stopping
When would the risk of withdrawal reaction would be increased ?
if antidepressant is stopped abruptly after taking for 8 weeks or more .
Must reduce gradually over four weeks. 6 months in patients on long term maintainance treatment.
Which antidepressants have higher risk of withdrawal reaction ?
Paroxetine, venlafaxine
How does TCAs work ?
Inhbitis the reuptake of 5 HT and NA
Which TCAs are less sedating ?
Imipramine
Lofepramine
Noritriptyline
They are given for apathetic, withdrawn patients
Which TCAs are better to give for anxious, agitated patients ?
Amitriptyline, clomipramine, dosulepin doxepin trimipramine, mianserin, trazadone
Describe TCAs cardiac side effects ?
QT prolongation, arrythmias, heart block, hypertension
Describe TCAs antimuscarinic side effects ?
dry mouth, blurred vision, constipation, tachycardia, urinary retention, pupil dilation, raised intraocular pressure, angle closure glaucoma
What are other side effects of TCAs?
seizures, hallucinations, mania, hypotension, sexual dysfunction, breast changes, EPS
When TCAs are given with carbamazepine what interactions occur?
Reduced TCAs levels since carbamazepine is a inducer + risk of hyponatraemia
Which TCAs particularly can cause QT prolongation ?
clomipramine
Which drugs given with TCAs can lead to hyponatraemia ?
LOOP/thiazide, desmopressin, carabamazepine,
Which drugs given with TCAs can cause QT prolongation ?
amiodarone, sotalol, antipsychotics, citalopram/escitalopram, loop/thiazide, B2 agonists, corticosteroids, theophylline
Which drugs given with TCAs can lead to hypotension ?
alpha blockers, BB, ACE, ARB, CCB
Antipsychotics, levodopa/dopaminergics, NSAIDs, SGLT inhibitors, Loop/thiazide diuretics, sildenafil
Which drugs given with TCAs can lead to increased antimuscarinic effects ?
antimuscarinic drugs, atropine, antihistamines
Which drugs given with TCAs can lead to an increased risk of serotonin syndrome ?
MAOIs, selegeline, tramadol, amfetamines, sumatriptan, SSRIs, ondansetron, lithium
How does monoamine oxidase inhibitors work ?
Prevent breakdown of monoamine neurotransmitters , which include dopamine, noradrenaline and serotonin,
With which two monoamine oxidase inhibitors hepatoxicicity is likely ?
phenelzine, isocarboxazid
Which monoamine oxidase inhibitor has the greatest stimulant action ?
tranylcypromine, more likely to cause hypertensive crisis
What symptoms would prompt to discontinue MOAI’s ?
palpitations or if frequent headaches occur. Discontinue if hypertensive crisis with throbbing headaches occur. Most likely to happen with tranylcypromine/
Which drugs given with MOAIs would lead to hypertensive crisis ?
pseudoephedrine, adrenaline, noradrenaline, levodopa, DRAs, MAO-B inhibitors
TCAs ( potentially lethal, especially tranylcypromine and clomipramine )
How should patients who receive MOAIs should be counselled ?
- They should avoid food containing tyramine ( mature cheese, wine, pickled herring, game, broad bean pods, marmite or similar yeast extracts, fermented soya bean products .
- Only eat fresh food, avoid stale or going off food.
- Avoid alcohol / de-alchoholised ( low alcoholic drinks )
