SSRIs & AntidepressantsShanthi AntillST3

What we will cover… General overview Indications for prescribing Choice of SSRI & side effects Current guidance Stopping & switching What to do if SSRIs don’t work Prescribing in special groups

SSRIs Selective serotonin reuptake inhibitors Increase extracellular level of serotonin by

limiting reabsorption into presynaptic cell Varying degrees of selectivity for other

monoamine transporters Main indications include depression, anxiety

+ OCD Advantages over TCAs include:

less sedative fewer anticholinergic SEs fewer cardiovascular SEs therefore safer in

OD Lesser effect on psychomotor performance

Side Effects Most common = GI, commonly nausea which is

dose related + often settles with use Others include:

Psychiatric – anxiety, panic attacks Neurological – tremor, seizures, serotonin syndrome CV - postural hypotension Metabolic - SIADH, hyponatraemia Hepatobiliary – abnormal LFTs MSK - myalgia, arthralgia Urological - urinary retention Reproductive - sexual dysfunction Skin - pruritus, rash,sweating, angioedema GI - nausea,vomiting, diarrhoea,dry mouth,GI bleeding Other – dizziness,insomnia, drowsiness, fatigue

Type Examples

SSRI – Selective serotonin reuptake inhibitor

CitalopramEscitalopramParoxetineFluoxetineSertralineFluvoxamine

SNRI – Selective noradrenaline reuptake inhibitors

DuloxetineVenlafaxineDesvenlafaxine

NaSSA - Noradrenergic and specific serotonergic antidepressants

Mirtazepine

SARI – Serotonin antagonist and reuptake inhibitor

Trazodone

TCA – tricyclic antidepressants AmitriptylineDosulepinDoxepinImipramine

Points to be aware of… Paroxetine – more weight gain, higher

rates of sexual dysfunction, more dangerous in withdrawal

Sertraline – higher rate of diarrhoea Citalopram/escitalopram – prolong QT

interval so consider other medications Fluoxetine – longer half-life compared to

rest of SSRI Mirtazepine – helps sleep, increases

appetite for carbs so often causes weight gain (can be helpful with certain patients)

Choice of treatment (1) Choice depends on:

Adverse effect profiles Patient preference Previous experience of treatment Likelihood to cause discontinuation

symptoms Safety in overdose

Choice of treatment (2) Cipriani et al, 2009 Compared 12 new generation

antidepressants Systematic review of 117 RCTs, 25928

participants from 1991-2007 Favoured escitalopram and sertraline

with regards to efficacy + favorability Sertraline as best choice when starting

treatment for moderate – severe depression in adults

NICE guidance… Depression – all SSRIs are licensed.

Paroxetine only for major depression Panic disorder – citalopram, escitalopram,

paroxetine Social anxiety – escitalopram, paroxetine OCD – fluoxetine, fluvoxamine, paroxetine,

sertraline PTSD – paroxetine, sertraline (only in

females) GAD - paroxetine

Starting SSRIs Before starting ensure patients are aware that they

may take a few weeks to work Review 1-2 weeks after starting treatment. A trial of at least 4-8 weeks (6 weeks in older

patients) should be given before deciding to discontinue/change an agent

If partial response, allow another 2 weeks to decide if effective or not

Little evidence to support use of dose escalation in patients who do not respond to standard doses

After remission of symptoms, continue for at least 4-6 months (12 months in the older patient)

Switching treatment No clear guidance on switching

antidepressants Maudsley Prescribing guidelines offers

table of advice. Note long half-life (1 week) of fluoxetine

affects regime MIMS/GP notebook have good online

reference tables when looking to switch

Stopping treatment Patients should be advised not to stop

treatment suddenly or omit doses. Drug and Therapeutics Bulletin advises:

after a 'standard' 6-8 months treatment it is recommended that treatment should be tapered off over a 6-8 week period

if the patient has been on long-term maintenance therapy then an even more gradual tapering e.g. by 1/4 of the treatment dose every 4-6 weeks.

if a course has lasted < 8 weeks then discontinuation over 1-2 weeks is safe

Discontinuation symptoms Review patients who are stopping/weaning

SSRIs regularly If suffering with any symptoms, consider

increasing dose & tapering even more cautiously

Generally begin within 24-72 hours of stopping and last approximately 1-2 weeks

Most commonly nausea, dizziness, headache and lethargy

Other symptoms include paraesthesia, 'shock-like' sensations, anxiety, tremor, balance problems, nightmares, insomnia and sweating

What if treatment doesn’t work?

Consider trying different SSRI Can try combining 2 antidepressants Venlafaxine & duloxetine thought to be good

in treatment resistant cases Can also try older agents depending on

experience Amitriptyline/nortriptyline Dosulepin

If still ineffective or unsure, refer secondary care Lithium augmention Antipsychotics

Prescribing in certain groups

Children/young people NICE state only after specialist review Fluoxetine 10mg first line, increased to 20mg if

needed after 1 week 2nd line – citalopram or sertraline

Post stroke depression – sertraline or mirtazepine Chronic disease – consider sertraline as lower

propensity for interactions with other medications Elderly – consider risk of falls with SSRIs/drug

interactions. Sertraline or citalopram good choices if required

Diabetes – diabetes double odds of co-morbid depression. Most data suggests fluoxetine most effective