Antidepressants Flashcards
What are the different types of antidepressants?
SSRIs SNRIs Mirtazapine (NaSSA) TCAs MAOIs
Which type of antidepressant is first-line for depression? Why?
SSRI
Similar efficacy to TCAs, but fewer adverse effects and safer in overdose
How do SSRIs work?
Reduces presynaptic reuptake of serotonin after release
Therefore, increases the concentration available for neurotransmission
Later on there is down-regulation of post-synaptic receptors (this is thought to be the long-term therapeutic effect and takes a couple of weeks)
What are the common side effects of SSRIs?
Restlessness/agitation on initiation (countered by BDZs) Nausea, GI disturbance Headache Weight changes (either direction) Sexual dysfunction (both men and women)
What are the less common side effects of SSRIs?
Bleeding
Suicidal ideation
Why do SSR|s cause bleeding?
Serotonin receptors found on platelets
Can cover with a PPI of at risk of peptic ulcers e.g. also taking NSAIDs/aspirin
Why can there be suicidal ideation in the first 2 weeks of taking SSRIs?
Due to the combination of increased motivation and lack of therapeutic effect as of yet
This is particularly relevant in the younger male population
Which are the 5 most common SSRIs? What are their doses (mgs)?
Sertraline (50-200) - therapeutic dose is 100, but start at 50 and increase Citalopram (20-40)/escitalopram (10-20) Fluoxetine (20-60) Paroxetine (20-60)
Which is usually the first-line SSRI? Why?
Sertraline
It is the safest in cardiac disease
Generally well-tolerated
Why is citalopram/escitalopram not used in older people?
QT prolongation
More of an issue if other drugs they are taking have the same effect
What do you have to be wary of when switching from fluoxetine and why?
Serotonin syndrome
This is due to its very long half life
The metabolites can stay in the system for days
What do you have to be wary of when stopping paroxetine and why?
Discontinuation syndrome
It has the shortest half life of all SSRIs
What are the monitoring requirements for SSRIs?
Within the first 2 weeks
Then every 2-4 weeks fir the first 3 months
Then at longer intervals e.g. 6 months
What are the interactions of SSRIs?
NSAIDs, Warfarin/heparin, Aspirin, Triptans, (drugs that increase risk of bleeding - need to co-prescribe gastroprotection), MAOIs
Atomoxetine (don’t give fluoxetine or paroxetine), antipsychotics (as they too prolong the QT interval)
What is discontinuation syndrome?
An unpleasant, but not life-threatening syndrome
Influenced by half-life (the shorter the half-life the bigger the problem)
What are the symptoms of discontinuation syndrome?
Sweating, shakes, agitation, insomnia, headaches, irritability, NV, paraesthesia, clonus
Which antidepressants are the most likely to trigger discontinuation syndrome?
Paroxetine
Venlafaxine
How can discontinuation syndrome be prevented?
Taper off by taking and not taking on alternate day/snapping tablets in half
Can also switch to fluoxetine and then reduce the fluoxetine
What is serotonin syndrome?
Due to excess serotonin in the system
Usually when SSRIs are combined with other antidepressants/tramadol
How does serotonin syndrome present?
Cognitive
- headaches, agitation, hypomania, confusion, coma
Autonomic
- shivering, sweating, hyperthermia, tachycardia, nausea, diarrhoea
Somatic
- myoclonus, hyper-reflexia, tremor
Triad of autonomic hyperactivity, altered mental state and neuromuscular excitation
What is the treatment for serotonin syndrome?
Supportive (fluids and monitoring)
What is the mechanism of action of SNRIs?
Acts in the same way as SSRIs, but also reduces noradrenaline reuptake
What can SNRIs also be used for apart from depression/anxiety?
Neuropathic pain
What are the side effects of SNRIs?
Same as SSRIs, but greater propensity for sedation, nausea and sexual dysfunction
What are the 2 SNRIs and what are their doses?
Duloxetine (60-120)
Venlafaxine (75-375)
Why must you be cautious with higher doses of venlafaxine in heart disease and why?
There is a high risk of cardiac arrhythmias and uncontrolled hypertension due to high adrenergic activity
Need to monitor blood pressure
Can patients with hepatic impairment take SSRIs?
Yes, but the dose may need to be reduced as SSRIs are metabolised by the liver
How are SSRIs prescribed?
Oral administration with tablets (citalopram can be given as oral drops that can be mixed with drinks - has a greater bioavailability so lower dosing).
Start at a low dose and then increased. Lower doses for elderly. Given once a day.
When can SSRIs be stopped?
Continue for 6 months after feeling better (2 years for recurrent) to prevent relapse. Avoid stopping suddenly.
What is the mechanism of mirtazapine?
It is a noradrenergic and specific serotonergic antidepressant. It inhibits alpha2 adrenoreceptors and 5HT-2 and 5HT-3 receptors.
What is the dose range for mirtazapine?
15-45
What are the side effects of mirtazapine and when is it given?
Has strong histaminic activity and so causes sedation and an increased appetite. It is given at night due to the sedative effects.
What are the indications for TCAs?
Second-line for moderate to severe depression Neuropathic pain (unlicensed) - lower doses
What is the mechanism of action of TCAs?
Blocks serotonin and NA reuptake. Also has effects on muscarinic, histaminergic and dopaminergic receptors which accounts for its high side effect profile.
Give examples of TCAs.
Amitriptyline
Lofepramine
Nortryptyline
What are the side effects of TCAs?
Antimuscarinic (dry mouth, constipation, blurred vision, urinary retention) Histamine blockade (sedation) Alpha1 blockade (hypotension) Dopamine blockade (breast changes, sexual dysfunction) Adverse cardiac effects (prolonged QT, arrhythmias) Brain effects (convulsions, hallucinations, mania)
Why are TCAs fatal in overdose?
QTc prolongation and arrhythmias
Particularly in the elderly
What is the mechanism of action of MAOIs?
Increase catecholamine levels (MAOI-A works more on serotonin and MAOI-B works more on dopamine)
Can only be prescribed by a psychiatrist
What type of depression are MAOIs more effective for?
Atypical depression (sleep and eat more) Dysthymia (subclinical depression)
Give examples of MAOIs and how safe they are in overdose.
Irreversible (more dangerous) - phenelzine, isocarboxazid
Reversible (less dangerous) - moclobamide, tranylcypromide
What is important to tell the patient when prescribing MAOIs?
Potential for significant and dangerous interactions with other drugs
Potential for tyramine reaction leading to a hypertensive crisis (avoid cheese, pickled meats, wine etc.) due to production of lots of adrenaline
If changing to another antidepressant - need a washout period of 6 weeks due to risk of serotonin syndrome
What is the mechanism of vortioxetine?
Increases serotonin
What are the indications of vortioxetine?
For resistant depression after already having tried 2 different antidepressants
What are the benefits of vortioxetine?
Well-tolerated with the most common side effect being nausea
Fairly cheap
Evidence for improvement in difficult to treat cognitive symptoms (memory and concentration)
How should you decide which antidepressant to chose?
If something has been used before and it was effective and well-tolerated - go with that one
In new cases - SSRI except
- if there is major weight loss or sleep difficulty use mirtazapine
- if there is comorbid neuropathic pain consider an SNRI
In most cases of SSRI has no effect try a different SSRI, still no effect switch to SNRI or mirtazapine
Sertraline is the first line SSRI as there are lower rates of seronin and discontinuation syndromes
How do you decide when to increase the dose of an antidepressant and when to switch?
For most people the effects should start in the first 2 weeks, but wait 4 weeks to make sure
If no benefit switch, if partial then increase
If significant side effects these may get better in a couple of weeks, but if still causing big problems switch
