Anti-depressants Flashcards
What is the four stepped care model?
Stepped Care is a system of delivering and monitoring mental health treatment so that the most effective, yet least resource intensive treatment, is delivered first, only “stepping up” to intensive / specialist services as required and depending on the level of patient distress or need.
What are the four steps?
Step 1: suspected depression
Step 2: mild to moderate depression
Step 3: moderate to severe depression
Step 4: severe and complex depression
At which step is anti-depressants the first line treatment?
Usually medication is seen as the first line from moderate depression onwards. However anti-depressants may be initiated in mild depression only if there is a past history of depressive episodes, already tried psychosocial interventions or there is a persistent subthreshold depressive symptoms for more than 2 years now.
When should psychosocial interventions be used in the management of depression?
First line for mild depression as low intensity and then used alongside medication as high intensity therapy in moderate depression onwards.
What is the first line management for suspected depression cases?
Support and psychoeducation on how to manage depression, physician may choose to monitor.
What are some examples of low intensity psychosocial interventions?
Guided self help book
Computer based CBT
What are some examples of high intensity psychosocial interventions?
Individual CBT
Interpersonal therapies
Relaxation therapies
Anxiety management
Mindfulness related therapies and counselling
ECT and TMS in severe and complex depression only
How does ECT work?
Electroconvulsive therapy (ECT for short) is a treatment that involves sending an electric current through your brain. This causes a brief surge of electrical activity within your brain (also known as a seizure). It is administered under anaesthesia and alongside a muscle relaxant (Profolol and Suxamethonium).
What are the risks of ECT?
Can cause vomiting so don’t eat beforehand and can cause amnesia so patients will be monitored and asked orientating questions.
What is anti-depressant choice based upon?
Duration of episode
Previous anti-depressant response
Likelihood of adherence, potential adverse effects and patient preference
What is the first line therapy for unipolar depression?
SSRIs which include:
Citalopram
Escitalopram
Fluoxetine
Sertraline
What is the dosing regimen for anti-depressants?
Apart from Mirtazapine all should be started at a lower dose due to being more tolerable and then increasing to target dose over a few days or weeks.
Why aren’t tricyclic anti-depressants not first line therapy?
Difficult to get to the therapeutic dose due to causing a wide range of side effects such as poor tolerability. Additionally they cause toxicity in overdose and have adverse drug reactions with alcohol.
If patients fail to respond to multiple anti-depressants what are the possible options?
May consider using Lithium, an anti-psychotic or another anti-depressant however this should also be in consideration of the increased side effect burden and the increased monitoring requirements.
Which anti-psychotics are licensed to be used in treatment resistant depression?
Aripiprazole
Olanzapine
Quetiapine
Risperidone
What are some examples of SNRI anti-depressants?
These work by inhibiting noradrenaline and serotonin reuptake. They include:
Duloxetine
Mirtazapine
Venlafaxine
Which SNRI combination is good for treatment resistant depression?
Mirtazapine and Venlafaxine
Why is Mirtazapine often prescribed at 30mg rather than 15mg?
As an SNRI it has greater noradrenergic activity at 30mg than at 15mg so is less sedating at higher doses.
Which SSRI is good to be used in the elderly?
Vortioxetine due to causing cognitive enhancement which is unrelated to anti-depressant mechanism
What is Quetiapine licensed for?
Licensed as an adjunctive therapy with partial anti-depressant response.
What are some of the second line SSRIs?
Fluvoxamine
Paroxetine
What are some of the second line related anti-depressants?
Agomelatine - helps improve sleep also
Reboxetine
Trazodone - antihistamine activity
What are the tricyclic antidepressants?
Amitriptyline
Dosulepin
Doxepin
Imipramine
Nortriptyline
Trimipramine
What is the usual dose for TCAs?
125-150mg a day although 5% of Caucasians are CYP 2D6 deficient and in those patients a much lower dose is used.
What are some of the MAO inhibitors used in depression?
These drugs irreversibly inhibit both MAO-A and B resulting in food/drink interactions including a tyramine free diet.
Examples:
Isocarboxazid
Phenelzine
Tranylcypromine
Moclobemide (Reversible inhibition of MAO-A - doesn’t have the same interactions)
Is St John’s Wort effective anti-depressant?
Mechanism of action is unknown, completely unlicensed and interactions with a lot of medications. Patients should not take this alongside anti-depressants.
Which anti-depressants have the highest efficacy and highest tolerability?
Agomelatine
Escitalopram
Vortioxetine
Which anti-depressants have the highest efficacy but lower tolerability?
Amitriptyline
Mirtazapine
Paroxetine
Venlafaxine
Which anti-depressants have a lower efficacy but higher tolerability?
Citalopram
Fluoxetine
Sertraline
Which anti-depressants have a lower efficacy and lower tolerability?
Fluvoxamine
Reboxetine
Trazodone
What is STAR*D?
STAR*D stands for Sequenced Treatment Alternatives to Relieve Depression was a collaborative study on the treatment of depression, funded by the National Institute of Mental Health. Its main focus was on the treatment of depression in patients where the first prescribed antidepressant proved inadequate.
According to STAR*D if a patient has partial/incomplete response what is the advised treatment?
Augment anti-depressants (to make larger; enlarge in size, number, strength, or extent; increase)
What was one of the key findings about switching anti-depressants?
Switching to another SSRI is as effective as other switches however the response goes down each time and therefore the first two anti-depressants that are tried - optimise this therapy by adjusting doses, times and managing side effects.
By continuing anti-depressants how does relapse risk reduce?
By 70% and efficacy continues up to 36 months post-treatment, perhaps even higher
When should SSRIs be taken?
Both SSRIs and SNRIs should be taken in the morning. This is because during dreaming serotonin and dopamine need to be supressed, by taking this medication at night therefore it prevents dreaming and leads to incomplete sleep, disrupted sleep architecture - no REM sleep.
When should Mirtazapine be taken?
At night due to serotonin reuptake inhibited by antagonism of 5-HT 2/3.
Which anti-depressants may help with sleep?
Those that have an antihistaminic side effect and Agomelatine is a melatonin receptor agonist and therefore leads to improved sleep.
How long do anti-depressants take to work?
Usually about 4 weeks to work.
Some response can be seen 2-6 weeks but optimal response is about 4-6 weeks.
Elderly can take longer to see a response
If there is no response to an anti-depressant after 4 weeks what should you do?
Check adherence following 4 weeks at the therapeutic dose and then switch anti-depressant
If there is only a minimal improvement to an anti-depressant after 4 weeks what should you do?
Continue to week 6
How frequent is monitoring for patients taking an anti-depressant?
Every 2-4 weeks for the first three months. May be less frequent if the treatment is working and more frequent if the patient is at risk.
If the patient has a tolerance issue with an anti-depressant what is an appropriate switch?
Trying one with a different mechanism of action, chemical group or another in the group
If the patient has a efficacy issue with an anti-depressant what is an appropriate switch?
Try a different class or mode of action
What is a good anti-depressant for switching?
Mirtazapine, not many interactions
What isn’t a good anti-depressant for switching?
Fluoxetine - need to have extra considerations due to its long half life especially with MAOIs.
TCAs also interact with SSRIs.
What are two cautions to bear in mind when switching anti-depressants?
Discontinuation syndrome (especially with Paroxetine and Venlafaxine due to their short half life)
Serotonin syndrome
What causes serotonin syndrome?
It is a toxic state due to increased serotonin levels within the brain.
Can be caused SSRIs, SNRIs and Tramadol
What are some of the symptoms of serotonin syndrome?
Restlessness
Myoclonus
Tremor and rigidity
Hyperreflexia
Shivering and elevated temperature
Arrhythmias
What are key drug interactions to minimalise risk of serotonin syndrome?
Do not use SSRIs alongside triptans or
Triptans with MAOIs.
How long should anti-depressants be prescribed for?
As the relapse rate of anti-depressants is high (40% within 2 years and 60% in 5 years) many will continue to reduce relapse so will take as long as needed.
Following the different episodes how long should anti-depressants be taken for to reduce relapse?
First episode: Six months post-recovery
Second episode: 1-2 years afterwards
Third episode: 3-5 years or longer significantly reduces relapse
Is there a link between anti-depressants and suicide?
Only in under 21s for the first couple of weeks of starting
When does discontinuation/withdrawal symptoms occur from anti-depressants?
1-3 days after stopping anti-depressants and normally short lived.
Can occur simply by missing a dose and is distinct from relapse which occurs earliest at 2 weeks.
What are some symptoms of SSRI withdrawal?
Dizziness
Light headiness
Agitation
Volatility
Electric shocks in the head
Nausea
Fatigue
Headache
Flu like symptoms
What are some symptoms of SNRI withdrawal?
Dizziness
Light headiness
Agitation
Volatility
Electric shocks in the head
Nausea
Fatigue
Headache
Flu like symptoms
In addition:
Restlessness
Abdominal distension
Congested sinuses
How should anti-depressants be withdrawn?
- Less than 8 weeks of treatment:
Withdraw over 1-2 weeks - After 6-8 months of treatment:
Taper over 6-8 week period
After long term maintenance reduce by 25% every 4-6 weeks.
What are the main side effects associated with SSRIs?
Anticholinergic side effects are rare
Nausea +++
Weight gain +
Sexual dysfunction but may be due to the condition
What are the main side effects associated with TCAs?
Anticholinergic side effects are common
Sedation +++
Hypotension +++
Nausea +
Sexual dysfunction +
Weight gain +++
What are the main side effects associated with SNRIs?
Anticholinergic side effects are rare
Sedation +
Hypotension +
Nausea +++
Sexual dysfunction +++
Weight gain +
What are the main side effects associated with NaSSAs?
Anticholinergic side effects are rare
Sedation ++
Weight gain +++
What are the main side effects associated with Trazodone?
Anticholinergic side effects are rare
Sedation ++
Hypotension +++
Nausea +++
Sexual dysfunction +
Weight gain +
What are the main side effects associated with MAO-I?
Anticholinergic side effects are common
Hypotension ++
Sexual dysfunction +
Weight gain +++
What is the appropriate management for blurred vision (anticholinergic side effect)?
Don’t drive
Side effect should wear off and if it doesn’t consider switching or adjusting the dose of the medication
What is the appropriate management for constipation (anticholinergic side effect)?
Lifestyle advice/exercise
Lactulose
What is the appropriate management for dry mouth (anticholinergic side effect)?
Suck a sweet/wine gum or mouth spray
Careful due to weight gain
What is the appropriate management for urinary retention (anticholinergic side effect)?
Medical emergency go to A+E
What is the appropriate management for anxiety (central side effect)?
Start at a lower dose and consider a stepwise progression
Could try splitting the dose daily
What is the appropriate management for seizures (central side effect)?
Some anti-depressants can lower the seizure threshold but it is rare
Usually will require a change in medication or a much slower titration
What is the appropriate management for dizziness (central side effect)?
Take in the evening
What is the appropriate management for confusion (central side effect)?
Rare except for TCAs will need a change or a slower titration in dose
What is the appropriate management for headache (central side effect)?
Try Paracetamol
What is the appropriate management for insomnia/sleep disturbances (central side effect)?
Take in the morning/split doses
What is the appropriate management for nausea (central side effect)?
Take with or just after food
Split the dose with breakfast and lunch time or try modified release
What is the appropriate management for sleepiness (central side effect)?
Due to the antihistaminic effect, don’t drive or use machinery and use Mirtazapine 30mg instead of 15mg.
How should hyponatremia associated with anti-depressants be managed?
Monitor carefully from onset for the first 30 days.
Symptoms can include:
Tiredness
Confusion
Headache
Inability to concentrate
Muscle cramps
Fits (refer immediately)
When is hyponatremia likely to occur?
Within 30 days of onset
After a dose change
If older or female
What is the appropriate management for postural hypotension?
Take care when standing up - try not to stand up too quickly
Don’t drive
Check Bp
What is the appropriate management if palpitations occur?
May need Beta blockers
Which anti-depressants are associated with the lowest risk of sexual dysfunction?
Mirtazapine
Agomelatine
What is the appropriate management for sexual dysfunction/loss of libido?
PDE5 inhibitors
Time dose when sexual activity is least likely or omit or delay dose for a short period
What is the appropriate management for excess sweating?
Dose adjust
What is the appropriate management for weight gain?
Adjust diet
Which anti-depressants have excess sedation when taken with alcohol?
Mirtazapine
Mianserine
Trazodone
Doxepin
Which antidepressants do not cause excess sedation when taken with alcohol?
SSRIs
Venlafaxine
Vortioxetine
Nortriptyline
Clomipramine
What is the interaction between SSRIs and NSAIDs?
Both increase the risk of gastric bleeds: SSRIs by 2 fold and then when taken alongside NSAIDs by an additional 3 fold.
What is the appropriate management between SSRIs and NSAIDs?
Use in caution in the elderly especially with SSRIs and NSAIDs known to cause gastric bleeds.
Risk can be mitigated by using PPIs.
Duloxetine is less of a problem.
Which anti-depressants do/don’t cause an increase in INR?
Those that do:
Paroxetine
Fluoxetine
Vortioxetine
Some reports with St John’s Wort, Duloxetine (careful when stopping), Venlafaxine
Those that don’t:
Sertraline
Citalopram
Some reports with St John’s Wort, Duloxetine, Venlafaxine
No report:
Mirtazapine
Reboxetine
Clomipramine
Which drug increases the risk of breast cancer recurrence when taken alongside Tamoxifen?
Paroxetine
Which anti-depressant interacts with smoking?
Smokers have their Duloxetine levels reduced by 50%.
What are some of the key interactions of St John’s Wort?
- Induces the metabolism of anti-retroviral
- HIV drugs
- Causes a rapid reduction in Ciclosporin levels and alters the metabolism ratio
- Reduces the effectiveness of the COC, EHC within 28 days of use. Use Copper IUD instead first line as 3mg of Levonorgestrel is unlicensed and affects Digoxin levels
Which anti-depressant affects Clozapine?
Fluvoxamine is a potent inhibitor of CYP 1A2 and therefore increases Clozapine levels. Other SSRIs can cause smaller increases in Clozapine levels
Which drugs interact with TCAs?
Carbamazepine induces CYP 3A4 reducing TCA levels by up to 50%
Valproate can double TCA levels
Cannabis can cause delirium, tachycardia, mania and other significant effects when taken with tricyclics
Triptans
Which age groups are at an increased risk of suicidal ideation?
Children and that is with all anti-depressants
Which anti-depressants are licensed for children?
Fluoxetine for ages 8-17 years if other methods haven’t worked
Sertraline is licensed for OCD between ages 16-17 years
What is the appropriate management for increased risk of suicide in young people?
Ensure to exclude a differential diagnosis before initiation on to medication such as bipolar depression for the patient to be initiated on a mood stabiliser and anti-depressant
Counsel the family to make them aware of suicidal ideation especially if agitated/akathisia after starting the anti-depressant
Start slowly on Fluoxetine 10mg/day - increase gradually with tolerance
What is the appropriate management of anti-depressants in pregnancy?
Weigh up risks vs benefits
Don’t use Paroxetine
Some link between SSRIs and autism
Little to no evidence of detrimental effect on postnatal development
What are the best anti-depressants to use in the elderly population?
SSRIs are better tolerated than TCAs but do have an increased risk of GI bleeds associated with them especially when taken with other meds that also increase this risk
Ensure dose is started low and titrated upwards slowly
What are some of the specific adverse effects that occur within the elderly?
Increased risk of hyponatremia
Postural hypotension
Falls
Haemorrhagic strokes with SSRISs
What are the main considerations regarding anti-depressants and cardiac disease?
Need to be aware of anti-platelet activity and CYP interactions with cardiac drugs
What are the most appropriate anti-depressants to use post-MI?
SSRIs and Mirtazapine have been shown to have a neutral or even beneficial effect on CVD mortality.
SSRIs are usually first line with Sertraline being the drug of choice as it may improve CVD risk factors - they don’t need to be withheld post-MI
Is CBT effective for patients with depression and CVD?
It was be ineffective post-MI but if they had depression beforehand it may be effective.
What other CVD effects do anti-depressants have?
Possibly have an anti-coagulant effect or indirect reduction in arrhythmia frequency.
Do Beta blockers induce depression?
Can induce depression but when post PICC can reduce the risk of depression
Which anti-depressants in particular are known to cause QT prolongation?
Citalopram
Escitalopram
What is the appropriate management for QT prolongation?
Citalopram and Escitalopram are contraindicated in known QT prolongation and cautioned if there is susceptibility to QT prolongation.
Avoid two medications causing QT prolongation
Monitor ECG
What are the main considerations for prescribing anti-depressants in renal impairment?
Some drugs are nephrotoxic and others can have the pharmacokinetic parameters altered by renal impairment
Potential for accumulation
Which is the preferred anti-depressant for renal impairment?
No preferred drug just make sure start low go slow
Anticholinergics may cause urinary retention and interfere with urea and electrolytes - may need to adjust.
What is the appropriate management for prescribing in hepatic impairment?
Start low and go slow, with regularly monitoring of LFTs although these may not directly correlate to the degree of impairment.
Which drugs need to be particularly cautious of in hepatic impairment>
Avoid drugs causing marked sedation and/or constipation
Paroxetine?
Extra caution is needed with drugs with a high first pass clearance
