Antidepressants and antianxiety medication Flashcards
Most sedating SSRI
Paroxetine
Reason for paroxetine’s sedating effect
High H1 affinity
SSRI with the highest rate of discontinuation symptoms
Paroxetine
SSRIs with the highest rates of drug interactions
Fluoxetine
Fluvoxamine
Paroxetine
SSRI which causes the most short term anxiety and agitation
Fluoxetine
SSRI which causes the most short term weight loss
Fluoxetine
SSRI which has the least drug interactions
Citalopram
SSRI which is most often used with elderly patients due to its lower risk of interactions
Citalopram
SSRI which has the most evidence for safe use post-MI
Sertraline
SSRI which is most often used for children and adolescents
Fluoxetine
Most common side effect of SSRIs
GI side effects
SSRI which causes the most GI upset
Fluvoxamine
SSRIs which cause the least sexual dysfunction
Vortioxetine
Fluvoxamine
SSRI which is the most anticholinergic
Paroxetine
Medication which should be co-prescribed if a patient is taking an SSRI and NSAID
Protein pump inhibitor
Drugs where SSRIs should be avoided where possible
NSAIDs
Warfarin
Aspirin
Triptans
SSRI which does not need to be gradually reduced when stopping
Fluoxetine
SSRI discontinuation symptoms
Restlessness Insomnia, vivid dreams Unsteadiness/dizziness Sweating GI symptoms - pain, cramps, diarrhoea, vomiting Paraesthesia, shock-like symptoms Flu-like symptoms Crying spells
Half life of citalopram
33 hours
Half life of escitalopram
30 hours
Half life of fluoxetine in early use
1-3 days
Half life of fluoxetine with prolonged use
4-6 days
Half life of fluvoxamine
17-22 hours
Half life of paroxetine
22 hours
Half life of sertraline
26 hours
Mechanism of action of MAOIs
Block the monoamine oxidase enzyme, which breaks down different neurotransmitters
Where MAO A is found
Placenta, gut, liver
Where MAO B is found
Brain, liver, platelets
Neurotransmitters MAO A breaks down
Serotonin, noradrenaline, dopamine, tyramine
Neurotransmitters MAO B breaks down
Phenylethylamine, methylhistamine, tryptamine, dopamine, tyramine
Types of MAOIs
Reversible or irreversible, selective for MOA A or MOA B, or non-selective
Irreversible and selective inhibitors of MAO B
Selegiline (no longer selective at high doses)
Reversible and selective inhibitor of MAO A
Meclobemide
Most common adverse effects
Dry mouth, nausea, diarrhoea, constipation, insomnia, dizziness/light-headedness
Cause of MAOI cheese reaction
Tyramine is a monoamine found in different foods which displaces noradrenaline from neurons, causing hypertension. When MAO doesn’t break down tyramine it can build up and cause a hypertensive reaction
Foods to avoid due to risk of cheese reaction
Cheese (except cream cheese and cottage cheese) Broad beans Alcohol Banana peels Bean curd Sauerkraut Yeast extracts (e.g. marmite)
First generation TCAs (tertiary amines)
Amitriptyline Lofepramine Imipramine Dosulepin Doxepin Clomipramine
Second generation TCAs (secondary amines)
Nortriptyline
Desipramine
Amoxapine
Most dangerous TCAs in overdose
Amitriptyline
Dosulepin - possibly the most dangerous
Common side effects of TCAs
Drowsiness Dry mouth Blurred vision Constipation Urinary retention
Features of overdose of TCAs
Sedation/coma Seizures Hypertension (early) then hypotension Tachycardia Broad complex dysrhythmias Increased anticholinergic side effects
ECG features of TCA overdose
Increased QRS - >100ms in lead II
Terminal R wave >3mm in aVR
Sinus tachycardia
Specific treatments for overdose of TCAs
IV sodium bicarbonate
Hyperventilation
IV lidocaine
Avoid 1a (procainamide) and 1c (flecainide) antiarrhythmics, beta-blockers and amiodarone
Drug interactions of TCAs
Cytochrome p450 inhibitors can lead to toxicity as TCAs are highly metabolised by cytochrome p450
Cytochrome p450 inducers can lead to treatment failure
MAOIs - contraindicated with some TCAs due to serotonin syndrome like reactions
QTc prolonging drugs
Mechanism of action of TCAs
Block the serotonin transporter and the noradrenaline transporter which leads to elevated synaptic concentrations of serotonin and noradrenaline
Weak affinity for the dopamine transporter
Antagonists of multiple receptors including 5-HT2
Inhibit sodium channels leading to their cardiotoxicity in overdose
Interaction of TCAs with warfarin
TCAs increase warfarin levels - high risk of bleeding
Interaction of TCAs with clonidine
TCAs decrease clonidine levels - risk of hypertension
Interaction of TCAs with MAOIs
Increase serotonin levels via synergistic serotonergic enhancement - increased risk serotonin syndrome like reaction
Decrease tyramine entry - reduced risk cheese reaction
Interaction between TCAs and levodopa
Reduces absorption of levodopa and so lowers efficacy
Active metabolite of amitriptyline
Nortriptyline
Active metabolite of clomiprimine
Desmethyl-clomipramine
Active metabolite of dosulepin
Desmethyldosulepin
Active metabolite of doxepin
Desmethyldoxepin
Active metabolite of imipramine
Desipramine
Active metabolite of lofepramine
Desipramine
Active metabolite of fluoxetine
Norfluoxetine
Active metabolite of mirtazapine
Demethyl-mirtazapine
Active metabolite of trazadone and nefazodone
mCPP
Active metabolite of venlafaxine
O-desmethyl-venlafaxine
Start dose of citalopram for depression
10-20mg/day
Maximum citalopram dose for depression
40mg/day
Start dose of escitalopram for depression
5-10mg/day
Maximum escitalopram dose for depression
20mg/day
Start dose of sertraline for depression
50mg/day
Maximum sertraline dose for depression
200mg/day
Start dose of fluoxetine for depression
20mg/day
Maximum fluoxetine dose for depression
60mg/day
Start dose of paroxetine for depression
20mg/day
Maximum dose of paroxetine for depression
50mg/day
Start dose of vortioxetine for depression
5-10mg/day
Maximum vortioxetine dose for depression
20mg/day
Start dose of venlafaxine for depression
75mg/day in divided doses
Maximum venlafaxine dose for depression
375mg/day
Start dose of mirtazapine for depression
15mg/day
Maximum mirtazapine dose for depression
45mg/day
Start dose of moclobemide for depression
300mg/day in divided doses
Usual dose of moclobemide for depression
Up to 600mg/day
TCA discontinuation symptoms
Flu-like symptoms
Insomnia
Excessive dreaming
MAOI discontinuation symptoms
Agitation
Ataxia and movement disorders
Insomnia
Vivid dreams
Discontinuation symptoms associated with agomelatine
Nil
Minimum effective dose of citalopram
20mg/day
Minimum effective dose of fluoxetine
20mg/day
Minimum effective dose of fluvoxamine
50mg/day
Minimum effective dose of paroxetine
20mg/day
Minimum effective dose of sertraline
50mg/day
Minimum effective dose of mirtazapine
30mg/day
Minimum effective dose of venlafaxine
75mg/day
Minimum effective dose of duloxetine
40-60mg/day
Minimum effective dose of agomelatine
25mg/day
Minimum effective dose of moclobemide
300mg/day
Minimum effective dose of trazadone
150mg/day
Starting dose of fluvoxamine
50-100mg/day
Maximum dose of fluvoxamine
300mg/day
Starting dose of agomelatine
25mg/day
Maximum dose of agomelatine
50mg/day
Starting dose of trazodone
150mg/day in divided doses
Maximum dose of trazodone
300mg/day generally
600mg/day in hospital inpatients
Non selective MAO A and MAO B inhibitors (all irreversible)
Hydrazine
Phenelzine
Tranylcypromine
Hydracarbazine
Antidepressant that can be given sublingually
Fluoxetine liquid
Antidepressants that can be given buccally
Selegiline
Amitriptyline
Antidepressants that can be given IV
Citalopram Escitalopram Mirtazapine Amitriptyline Clomipramine Ketamine
IM antipsychotic which has been shown to have antidepressant effects
Flupentixol
Antidepressant that can be given transdermally
Selegiline
Antidepressants that exist as suppositaries
Amitriptyline
Clomipramine
Imipramine
Trazodone
TCA side effects
Antimuscarinic - dry mouth, urinary retention Weight gain Sedation Sexual dysfunction Cognitive impairment Arrhythmias Black hairy tongue Tremor Altered LFTs Paralytic ileus NMS
Active metabolite of sertraline
Desmethylsertraline
Dose at which antianxiety effects of trazadone appear compared to antidepressant effects
Antianxiety effects occur at lower doses
Number of times a day buspirone is given
3
Active metabolite of buspirone
1-pyrimidinylpiperazine
Impact of bupropion on seizures
Dose related risk of seizures
Worse with instant release preparations
Treatment combinations with good evidence for treatment resistant depression
SSRI or venlafaxine PLUS mirtazapine or mianserin
Treatment combination for treatment resistant depression known as ‘California rocket fuel’
SNRI and mirtazapine
Enantiomers present in citalopram
R and S
Enantiomer present in escitalopram
Pure S enantiomer
Benefit to using escitalopram rather than citalopram
R enantiomer of citalopram has antihistaminic properties - using escitalopram removes these
Citalopram has inconsistent therapeutic action due to the R enantiomer and dose often needs to be increased, but can’t due to QTc prolongation - using escitalopram lower doses can often be used and there are no higher dose restrictions to avoid prolonging the QTc
Main clinical use for buspirone
Generalised anxiety disorder
Hormone given to treat depression
Thyroid hormone
TCA which is most preferable with elderly patients
Lofepramine
Age group who clear TCAs fastest
Children/adolescents
SSRI most selective for serotonin reuptake
Citalopram
SSRI with the longest half life
Fluoxetine
SSRI active metabolite with the longest half life
Norfluoxetine
Antidepressant which shows autoinduction
Paroxetine
Mechanism by which TCAs delay their own absorption
Anticholinergic effects
Time after stopping SSRI when discontinuation symptoms have usually started
By day 5
Discontinuation symptom specific to paroxetine
Suicidal ideation
SSRI which causes the most sexual dysfunction
Paroxetine
SSRI which causes the most weight gain
Paroxetine
First line antidepressant for patients with diabetes
Fluoxetine
Drugs to avoid with MAOIs
SSRIs SNRIs TCAs - clomipramine and imipramine only Opioids St John's Wort Triptans OTC cold medication - dextromethorphan and chlorpheniramine
SSRI which can be used to help prevent discontinuation symptoms from venlafaxine and clomipramine
Fluoxetine
TCA which shows the highest rates of anticholinergic side effects
Imipramine
Time frame to develop antidepressant related hyponatraemia
Usually within the first 30 days
Antidepressant which most improves sleep wake cycles in major depression
Agomelatine
Alternative name for dosulepin
Dothiepin
Most sedating tricyclics
Amitriptyline
Dothiepin
Effect on receptors of chronic administration of tricyclics
Causes down-regulation of beta-adrenergic receptors
TCA with the most stimulant effect
Desipramine
Medication of choice to treat a hypertensive crisis caused by combination of MAOI and tyramine containing food
Alpha adrenergic antagonist e.g. phentolamine, chlorpromazine
Antidepressants known for causing weight gain
TCAs
Mirtazapine
TCA with the highest antihistaminergic activity
Doxepin
SSRI which should be used with the most caution post-MI
Citalopram
Effect of bupropion on weight
Moderate sustained weight loss
Specific side effect of mianserin that requires regular monitoring
Bone marrow suppression
Side effect associated with venlafaxine and bupropion which can be helped by alpha and beta blockers
Sweating
Common side effects of MAOIs
Postural hypotension Insomnia Peripheral oedema Restlessness Nausea Dizziness Sexual dysfunction Sweating Tremor
Antidepressant associated with closed angle glaucoma
Paroxetine
Principle cause of death in TCA overdose
Cardiac arrhythmia
SSRI which is present to high concentrations in breast milk
Fluoxetine
Risk factors for antidepressant induced hyponatraemia
Old age
Female sex
Low BMI
Concomitant use of diuretics
Antidepressant which can cause dependence
Tranylcypromine
Antidepressant which can directly influence gene transcription through nuclear receptors
Tri-iodothyronine
Medical condition where the use of MAOIs is contraindicated
Phaeochromocytoma
Antidepressant with good efficacy in patients with atypical depression
Phenelzine
Antidepressants least likely to precipitate mania in a patient with bipolar disorder
Bupropion
Sertraline
Blood test required before starting agomelatine
LFTs
Timing of LFTs required in patients taking agomelatine
Baseline
3, 6, 12, and 24 weeks after starting treatment
Antidepressants to consider in patients who have developed antidepressant related hyponatraemia
Nortriptyline
Lofepramine
MAOIs
Likely mechanism of action of SSRI discontinuation syndrome
Temporary deficiency in the brain of one or more essential neurotransmitters associated with mood
Antidepressants known as dual action antidepressants
Venlafaxine
Duloxetine
Impact of smoking on duloxetine plasma levels
Reduced by up to 50%
Mechanism behind the increased risk of bleeding with SSRIs
SSRIs inhibit the serotonin transporter which is responsible for the uptake of serotonin into platelets
Depleted platelet serotonin leads to inability to form clots
SSRIs increase gastric acid secretion which acts as an irritant to the gastric mucosa, increasing the risk of GI bleeding
Antidepressant most associated with waves of withdrawal symptoms
Venlafaxine
SSRI with the shortest half life
Fluvoxamine
Most serotonergic TCA
Clomipramine
Reversible inhibitor of MAO that does not react with tyramine
Moclobemide
Antidepressant treatment combination known as California rocket fuel for its effects in treatment resistant depression
Mirtazapine and venlafaxine
Antidepressant suggested for patients with hyponatraemia
Agomelatine
Mechanism of action of the delayed onset part of antidepressant medication action
Down regulation of HT1A autoreceptors in the post-synaptic neurons
Antidepressant classes which cause an increased risk of postpartum haemorrhage
All classes
Antidepressant causing the least sexual dysfunction
Agomelatine
Time to wait after stopping a MAOI before starting another antidepressant (particularly an SSRI)
2 weeks
Least sedating TCAs
Imipramine
Lofepramine
Nortriptyline
Main side effects of buspirone
Dizziness Headache Excitement Nausea Dry mouth
Most notable side effect of ketamine
Dissociation
TCA which causes the most weight gain
Doxepin
Antidepressant associated with raised cholesterol levels
Mirtazapine
Antidepressant discontinued due to risk of severe liver damage
Nefazodone
Antidepressants least influenced by pharmacokinetic factors
MAOIs