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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 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 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 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, 'shocklike' 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