Antidepressants Flashcards
Which drugs impact on all aspects of sexual dysfunction?
Duloxetine
MAOIs
SSRIs
Trazodone
Tricyclics
Venlafaxine
What is the management of sexual dysfunction secondary to antidepressants?
1 - rule out other causes
2 - switch to lower risk antidepressant
3 - consider non-pharma strategies (does reduction / drug holidays)
4 - consider pharmacological options (most evidence to support phosphodiesterase inhibitors / sildenafil, mirtazapine augmentation also a reasonable option)
What antidepressants are indicated in nocturnal enuresis in children?
Amitriptyline
Imipramine
Nortriptyline
What antidepressants are licensed in phobic and obsessional states?
clomipramine
What antidepressant is licensed in cataplexy associated with narcolepsy?
clomipramine
What antidepressant is licensed in panic disorder and agoraphobia?
citalopram
escitalopram
sertraline
paroxetine
venlafaxine
What antidepressant is licensed in social anxiety/phobia
Escitalopram
Paroxetine
Sertraline
Venlafaxine
Moclobemide
What antidepressant is licensed in OCD
Escitalopram
Fluoxetine
Sertraline
Fluvoxamine
Paroxetine
Clomipramine
What antidepressant is licensed in GAD
Escitalopram
Paroxetine
Duloxetine
Venlafaxine
What antidepressant is licensed in bulimia?
Fluoxetine
What antidepressant is licensed in PTSD?
Paroxetine
Sertraline
Give examples of SSRIs
Fluoxetine
Sertraline
Citalopram
Escitalopram
Vortioxetine
Dapoxetine
Paroxetine
Fluvoxamine
Which SSRI is associated with higher incidence of discontinuation symptoms?
Paroxetine
What SSRI causes the most short term weight loss and anxiety/agitation?
Fluoxetine
Which SSRI is useful in elderly patients and why?
Citalopram as it is associated with lower risk of drug interactions
Which SSRI is most useful post MI?
Sertraline
Which SSRI is the drug of choice in children and adolescents?
Fluoxetine
What is the most common SE of SSRIs?
GI sympytoms
Which SSRI is most sedating?
Paroxetine
Which SSRI is least associated with sexual dysfunction?
Vortioxetine
Also mirtazapine
Which SSRI causes the most GI upset?
Fluvoxamine
Which SSRI is the most anticholinergic?
Paroxetine
Which SSRIs have a higher propensity for drug interactions?
Fluoxetine
Fluvoxamine
Paroxetine
Which SSRIs are more suitable for patients with chronic physical health problems?
Citalopram
Sertraline
What drugs mean SSRIs should be avoided?
Warfarin
Triptans
NSAIDs or prescribe with PPI
When should patients be reviewed after commencing antidepressants? what if theyre under 30/increased risk of suicide
After 2 weeks
After 1 week
How long should patients be continued on antidepressants after remission?
6 months
Over how long should SSRIs be gradually reduced over when stopping?
4 weeks
What are discontinuation symptoms?
Increased mood change
Restlessness
Difficulty sleeping
Unsteadiness
Sweating
GI symptoms - pain, cramping, diarrhoea, vomiting
Paraesthesia
Which SSRIs carry a higher risk of EPSEs?
Paroxetine
Escitalopram
Citalopram
What is the half life of citalopram?
33 hours
What is the half life of esctialopram?
30 hour s
What is the half life of fluoxetine?
4-6 days
What are the major interactions of fluoxetine?
Inhibits CYP2D6 and CYP3A4
Increases levels of some antipsychotics, some benzos, carbamazepine, ciclosporin, phenytoin, tricyclics
What type of drugs should fluoxetine never be used with?
MAOIs
What is the half life of fluvoxamine?
17-22 hours
WHat are the interactions of fluvoxamine?
Inhibits CYP1A2, CYP2CP and CYP3A4
Increases levels of some benzos, carbamazepine, ciclosporin, phenytoin, TCAs. methadone, olanzapine, clozapine, propranolol, theophylline, warfarin
What is the half life of paroxetine?
22 hours
Whate interactions are there with paroxetine?
Potent inhibitor of CYP2D6 and CYP3A4 increasing levels of some antipsychotics and TCAsW
What should paroxetine never be used with?
MAOIs
What is the half life of sertraline?
26 hours
What are the interactions of sertraline?
Inhibits CYP2D6 increasing levels of some antipsychotics and tricyclics
Which SSRIs should be avoided with St Johns wort?
Sertraline
Paroxetine
Fluoxetine
What antidepressants hasnt hyperprolactinaemia been reported in?
Mirtazapine
Agomelatine
Bupropion
Vortioxetine
What is the mechanism of action of MAOis?
Inhibits monoamine oxidase enzyme
This enzyme breaks down several neurotransmitters in the brain: noradrenaline, serotonin, dopamine and tyramine
What is metabolised by MAO-A
Serotonin
Noradrenaline
Tyramine
Dopamine
What is metabolised by MAO-B?
Phenethylamine
Dopamine
Where is MAO-A mainly found?
Placenta
Gut
Liver
Where is MAO-B mainly found?
Brain liver and platelets
What are the adverse effects of MAOIs
Orthostatic hypotension
Daytime drowsiness
Insomnia
Nausea
Weight gain
Muscle pain
Myoclonus
Paraesthesia
Sexual dysfunction
What drugs should be avoided with MAOis?
SSRIs
SNRIs
TCAs - clomipramine and imipramine
Opioids
St John’s wort
Cold remedies
Triptans
What are the main issues caused by interactions with MAOis?
Serotonin syndrome
Raised blood pressure
Which TCAs specifically elevate the risk of serotonin syndrome with MAOis?
Clomipramine
Imipramine
Explain the MAOI cheese reaction
Monoamine oxidase, located in the gastrointestinal tract, neutralises tyramine. If drugs inhibit the breakdown of ingested tyramine, it gets absorbed, displacing norepinephrine from sympathetic nerve endings and epinephrine from the adrenal glands. When large amounts of pressor amines are released, symptoms such as severe occipital or temporal headaches, sweating, pupil dilation, neck stiffness, palpitations, and elevated blood pressure might arise.
What foods must be avoided with MAOis?
matured/aged cheeses
fermented sausages
poorly stored meats
Broad bean pods
Banana skin
Draught beer
Marmite
Sauerkraut
Soy sauce
What type of antidepressant is mirtazapine?
Noradrenaline and serotonin specific antidepressant (NaSSa)
What percentage of pts develop discontinuation syndrome after abruptly stopping or marked reduction?
20%
When do discontinuation symptoms typically start after stopping?
5 days
How long do discontinuation symptoms last? Give the mean duration of SSRIs
1day - 3weeks
5 days mean
WHat are sx of SSRI discontinuation syndrome?
Flu-like symptoms
Anxiety and suicidality
Mood and concentration changes
Stomach upset (nausea, diarrhoea)
Dizziness and imbalance
Insomnia
Vivid dreams
Irritability
Crying spells
Sensory symptoms (e.g. paraesthesia’s or brain zaps, sensations resembling electric shocks)
FINISH, which stands for Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory disturbances, and Hyperarousal (anxiety, irritability).
Which ADs are most likely to result in discontinuation syndrome?
Paroxetine
Venlafaxine
Which AD is least likely to result in discontinuation syndrome?
Fluoxetine
What are symptoms of TCA discontinuation syndrome?
Flu-like symptoms
Insomnia
Excessive dreaming
What TCAs are particularly associated with discontinuation syndrome?
Amitriptyline
Imipramine
What are symptoms of MAOI discontinuation syndrome?
Agitation/ irritability
Ataxia
Movement disorders
Insomnia
Vivid dreams
Which MAOIs are particularly associated with discontinuation syndrome?
All of them
What are the biggest risk factors for discontinuation syndrome?
those on antidepressants with shorter half lives
those who have been taking antidepressants for 8 weeks or longer (longer duration of treatment)
those using higher doses
those who developed anxiety symptoms at the start of antidepressant therapy
those receiving other centrally active medications (e.g. antihypertensives, antihistamines, antipsychotics)
younger people
those who have experienced discontinuation symptoms before
those also prescribed antipsychotics`
Which antidpressant is not associated with any discontinuation syndrome?
agomelatine
Give examples of secondary (second generation) amines?
Desipramine
Nortriptyline
Protriptyline
Amoxapine
Describe the mechanism of secondary amines?
Primarily inhibit the reuptake of noradrenaline which increases its levels in the synaptic cleft and enhances its transmission.
Associated with improved mood and analgesic effects.
What are the side effects of secondary amines?
Noradrenergic:
dry mouth
constipation
urinary retention
tachycardia
mild sedation
Which type of amine is preferred in elderly patients?
secondary
Give examples of tertiary (first generation) amines
Amitriptyline
Lofepramine
Imipramine
Clomipramine
Dosulepin (Dothiepin)
Doxepin
Trimipramine
Butriptyline
Describe the mechanism of tertiary amines
Inhibit the reuptake of serotonin and noradrenaline increasing their levels in the synaptic cleft and enhancing their transmission.
Makes them effective in treating depression
Give the side effects of tertiary amines
Sedation
Orthostatic hypotension
Anticholinergic - dry mouth, constipation etc
Weight gain (antihistaminic and anticholinergic effects)
Cardiotoxicity
When are tertiary amines preferable in the treatment of depression?
More potent antidepressant effects particularly in severe depression where a stronger serotonergic component is beneficial
What are side effects seen in TCAs?
Dry mouth (xerostomia)
Sedation
Constipation
Blurred vision
Weight gain
Dizziness
Retention
Postural hypotension
Tachycardia
Sweating
Cognitive impairment
Sexual dysfunction
Increased appetite
Headache
Tremor
Nausea
Palpitations
Which TCA in particular causes increased appetite?
amitriptyline
Which TCAs are especially linked to sweating?
clomipramine
What are important TCA side effects to be aware of?
Arrhythmias
Black tongue
Altered LFTs
Tremor
NMS
Which TCA is the safest in overdose?
Lofepramine
Which 2 TCAs are the most dangerous in overdose?
Amitriptyline
Dosulepin
Which antidepressants are available IV?
M-irtazapine
E-scitalopram
C-italopram
C-lomipramine
A-mitriptyline
Which antidepressant is available sublingually?
fluoxetine as liquid
Which AD is available via buccal route?
Selegiline
Crushed amitriptyline
Which medication is available IM?
IM flupentixol
Which AD can be given transdermally?
Selegiline
Which ADs can begiven rectally?
Sertraline
Doxepin
Which AD is associated with torsades de pointes?
Citalopram
Which ADs should be avoided in those at risk of arrhythmia?
Buproprion
Citalopram
Escitalopram
Meclobemide
Lofepramine
Venlafaxine
What ECG changes can be seen with TCAs?
PR, QRS and QT prolongation
Brugada syndrome
What causes ECG changes with TCAs?
Potent blockade of cardiac sodium channels and variable activity at potassium channels
Slows action potential and provides a membrane stabilising effect
Is arrhythmogenic potential of ADs dose related?
Yes
What scale is most helpful for evaluating discontinuation symptoms?
DESS (Discontinuation-Emergent Signs and Symptoms)
What is the forced swim test? What is it also known as?
behavioural assay to assess depressive like states and efficacy of AD treatment in rodents
Porsolt Swim Test
Explain how the forced swim test is carried out
Place a rodent in a cylindrical container filled with water from which it cannot escape.
Then two sessions.
1. Training session - placed in the water for an initial period then dried and returned to its cage
2. Test session - after 24hrs the animal is placed in the water again for a shorter duration
What are the possible results and interpretation of the forced swim test?
Results:
1. Immobility - remains floating in the water making only movements necessary to keep its head above the water
2. Swimming
3. Climbing - makes vigorous movements usually towards the walls of the container
Interpretation:
1. Immobility time - increased immobility time is interpreted as a measure of depressive like behaviour
2. Effect of ADs - effective ADs reduce immobility time and increase active behaviours (swimming or climbing)
