SSRIs & Antidepressants Shanthi Antill ST3

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 Developed over very short period of time in the early 1970s. Varying degrees of selectivity for norepinephrine and dopamine which accounts for differences between SSRIs Aside from main indications, also have a place in treatment of eating disorders, GAD, stroke recovery, premature ejaculation

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 SEs are often dose related and most settle with continued use. Also some SEs specific to the individual SSRI (discussed later)

SSRI – Selective serotonin reuptake inhibitor Citalopram Escitalopram Type Examples SSRI – Selective serotonin reuptake inhibitor Citalopram Escitalopram Paroxetine Fluoxetine Sertraline Fluvoxamine SNRI – Selective noradrenaline reuptake inhibitors Duloxetine Venlafaxine Desvenlafaxine NaSSA - Noradrenergic and specific serotonergic antidepressants Mirtazepine SARI – Serotonin antagonist and reuptake inhibitor Trazodone TCA – tricyclic antidepressants Amitriptyline Dosulepin Doxepin Imipramine Brief overview of the classes most commonly used today

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) Can effect prescribing.

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 Cipriani 2009 study most recent and only study which compared all the major antidepressants.

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 Generally choosing an SSRI for a particular patient based on personal experience/anecdotal

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) Although guidance says to trial for at least 4-8 weeks, psychiatrists say that if ineffective after 2-4 weeks, should increase dose or change the agent.

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

Useful to refer to when switching Useful to refer to when switching. Obviously would need to cater this for the individual patient i.e. some may experience more withdrawal symptoms than others.

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 Review every 2-3 weeks. If struggling with a dose reduction, may need to go back to previous dose and then wean a lot more slowly

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