Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Neuropharmacology wikipedia , lookup
Prescription costs wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Discovery and development of direct thrombin inhibitors wikipedia , lookup
National Institute for Health and Care Excellence wikipedia , lookup
Pharmacokinetics wikipedia , lookup
Adherence (medicine) wikipedia , lookup
Dextropropoxyphene wikipedia , lookup
Medicines Q&As Q&A 369.2 What is the first choice antidepressant for patients with renal impairment? Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp Date prepared: Oct 2014 Background Depression is a common psychiatric disorder which can be caused and exacerbated by chronic physical health problems [1-2]. Patients with chronic kidney disease, especially severe renal impairment (RI) have been shown to be at higher risk of depression [2]. It has been shown that antidepressant prescribing rates are lower in patients on dialysis despite the increased prevalence of depression [3]. There is a lack of controlled trial data for the treatment of depression in RI and this together with concern over antidepressant side effects may contribute to reduced prescribing of antidepressants in RI [3]. The use of antidepressants in renal replacement therapies is not discussed here. Answer Most antidepressants can be used with caution in RI [3-9] since the majority are hepatically metabolised and do not significantly accumulate, even in severe RI [3-9]. The main issues surrounding prescribing antidepressants for patients with RI are therefore much the same as for those patients with normal renal function, where the effects of age, comorbidities and the potential effects of other medications taken concurrently need to be considered. In addition patients with renal impairment have specific increased risks including gastrointestinal bleeding, cardiovascular disease and cerebral sensitivity to sedating medications which also need to be considered. In line with NICE guidance [1-2], the most appropriate antidepressant should be chosen based on: Any anticipated adverse events, for example side effects and discontinuation symptoms and potential interactions with concomitant medication or physical health problems The patient’s perception of the efficacy and tolerability of any antidepressants they have previously taken. NICE guidelines state that there is no evidence as yet supporting the use of specific antidepressants for patients with particular chronic physical health problems [1-2]. They recommend that when an antidepressant is to be prescribed, a SSRI is usually chosen first line as they are equally effective as other antidepressants but have a favourable side effect profile; citalopram and sertraline are particularly recommended as they also have less propensity to interact compared with other SSRIs [1-2].This advice is not specific to RI. Table 1 contains a summary of the information from the manufacturer’s product information, Renal Drug Handbook and The Maudsley Prescribing Guidelines for a range of antidepressants. The Maudsley Prescribing Guidelines state that no agent is clearly preferred over another in RI however citalopram and sertraline may be reasonable choices [5]. The Psychotropic Drug Directory assesses antidepressants in terms of risk in RI as follows [6]: Lower risk – agomelatine, mianserin, moclobemide, TCA’s, trazodone, tryptophan Moderate risk – duloxetine, MAOIs, mirtazapine, reboxetine, SSRIs (except sertraline) Higher risk – venlafaxine, fluoxetine, sertraline Available through NICE Evidence. Search at www.evidence.nhs.uk 1 Medicines Q&As Both The Psychotropic Drug Directory and The Maudsley Prescribing Guidelines provide information on individual drugs where available [5,6]. The Psychotropic Drug Directory considers sertraline a higher risk antidepressant, compared with the recommendation in The Maudsley Guidelines. This view is based on a study of 12 patients with end stage renal disease who were on maintenance haemodialysis and were taking 25mg/day sertraline. All 12 showed signs of serotonin syndrome and 11 discontinued within 3 weeks. The Renal Drug Handbook [4] suggests no dose reduction is required with sertraline in various stages of RI whereas Nagler et al [9] suggest dosage reduction of sertraline is required in patients with severe RI (eGFR <30mL/min). The majority of information regarding the use of antidepressants relates to pharmacokinetic studies or to patients undergoing dialysis and there is limited data on clinical use in RI prior to dialysis. Reviews by Hedayati et al [3] and Nagler et al [9] provide information on most antidepressants in RI, including pharmacokinetic data, where available, and both reviews suggest that SSRIs be considered as a first choice although specific agents are not mentioned. Raymond et al [8] and Nagler et al [9], highlight that few studies have evaluated the clinical efficacy of antidepressants in RI but state that there is most evidence for the use of SSRI’s. Raymond et al., apply the principles of prescribing antidepressants for the general population to those with renal disease and suggest that newer drugs such as SSRIs, venlafaxine and mirtazapine are generally favoured over TCA’s and MAOIs due to their safety profiles, with choice of a particular agent based on adverse effects and interactions [8]. Hyponatraemia has been associated with all antidepressants, although it has been reported more frequently with SSRIs; reduced renal function is a risk factor for developing hyponatraemia [10-11]. Particular caution may be required when switching between antidepressants as half lives of individual agents may be increased in RI [4,6,7]. Wash out periods, where advised, may need to be extended to take this into account. The Maudsley Guidelines specifically recommend vigilance in monitoring for serotonin syndrome in patients with RI prescribed antidepressants [5]. Selective Serotonin Reuptake Inhibitors (SSRIs) SSRIs are often recommended as the agents of choice in RI [3, 5, 9] although there is a lack of robust evidence to support this recommendation and therefore it is mainly based on pharmacokinetic data and clinical experience [3, 7, 9]. Reviews by Nagler et al [9] and the Cochrane Collaboration [12] have demonstrated the paucity of information available on the use of antidepressants, including SSRIS, in RI and renal replacement therapies. SSRIs are predominantly hepatically metabolised and some SSRIs alter the kinetics of CYP450 enzymes [13-19]. In general SSRIs do not require a dose adjustment in RI, however as some metabolites are renally excreted, caution is required [4,13-18]. The half life and plasma concentration of paroxetine have been shown to increase as renal function declines and lower starting doses are recommended by most sources [4,5,7,8,16] Drug interactions may be a problem with the SSRIs that affect CYP450 enzymes. Fluoxetine, fluvoxamine and paroxetine in particular may interact with other medicines via this mechanism [1, 8]. Fluoxetine has been shown to be efficacious and well tolerated in in dialysis patients [7]; however it may not be the most appropriate first-line agent due to its extended half-life and interaction potential [1, 5, 7-8].(See notes above regarding citalopram and sertraline). SSRIs are associated with an increased bleeding risk which may be a concern in RI [3, 8,11]. Tricyclic Antidepressants (TCAs) Historically TCAs were the agents of choice in RI due to more experience of their use, but they have been superseded by the SSRIs due to safety concerns and adverse effects with TCAs [3, 8]. Amitriptyline and dosulepin are effective but they are particularly dangerous in overdose and NICE [1dosulepin only] and the BNF do not recommend their use in the treatment of depression [11]. Although most TCAs can be used cautiously in RI, as in patients with normal renal function, they are generally not recommended as first-line antidepressants. Available through NICE Evidence. Search at www.evidence.nhs.uk 2 Medicines Q&As The majority of TCAs are hepatically metabolised and most do not alter the kinetics of enzymes in the CYP450 pathway [18-19, 20-26]. Interactions with other medicines metabolised via the CYP450 pathway are therefore less likely than with the SSRIs, but numerous other interactions occur [11, 18-19, 20-26]. Lofepramine, of which approximately 50% is renally excreted, is contraindicated by its manufacturer in severe RI [6, 24]. TCAs’ antimuscarinic adverse effects may be more pronounced in RI, and all patients given TCAs should be monitored for urinary retention, confusion, sedation and postural hypotension [5]. Cardiac adverse effects, e.g. hypotension and arrhythmias, may also be a problem in patients with RI and coexisting cardiovascular disease [3, 8]. Miscellaneous Antidepressants As Duloxetine is a relatively new antidepressant there is only limited experience of its use in RI. Duloxetine is contra-indicated in patients with creatinine clearance (CrCl) of less than 30mL/min [5,27]. Duloxetine is extensively metabolised by the CYP450 pathway to mainly inactive metabolites and it has been shown to accumulate in dialysis patients [7, 27]. Duloxetine has also been associated with increases in blood pressure, and patients with known hypertension or other cardiac disease or whose condition may be affected by an increase in blood pressure should have their blood pressure monitored [10]. Mirtazapine is extensively metabolised via the CYP450 pathway to active and inactive metabolites which are mainly excreted in the urine [18, 28]. Clearance of mirtazapine is reduced in moderate to severe RI (CrCl <40mL/min) and the manufacturers advise that this should be taken into account when prescribing mirtazapine [28]. Mirtazapine exhibits weak antimuscarinic effects [11, 28]. Moclobemide is extensively metabolised by the liver, in part by CYP450 enzymes, to mainly inactive metabolites, which are renally excreted [18, 29]. No dose alteration is required in RI as RI has not been shown to alter the elimination of moclobemide [29]. Moclobemide is claimed to have a reduced risk of interactions and to cause less potentiation of the pressor effect of tyramine than other MAOIs, but patients should still be advised to avoid consumption of large amounts of tyramine rich foods and to avoid taking sympathomimetics [11]. Reboxetine has been shown to be metabolised predominately by the CYP450 pathway in in vitro studies, to inactive metabolites, which are renally excreted [18,30]. Reboxetine is not thought to have any clinically significant effects on CYP450 enzymes [18,30]. Systemic exposure and half life are approximately doubled in patients with renal insufficiency and therefore the manufacturer recommends a 50% reduction in starting dose for patients with RI [30]. The manufacturers of reboxetine do not recommend its use in the elderly due to limited evidence of its use in this patient group [30]. Venlafaxine is extensively metabolised via the CYP450 pathway to active metabolites which are mainly excreted in the urine [18, 31]. The half lives of venlafaxine and its metabolites have been shown to increase in RI [7, 18]. The manufacturer recommends reducing the dose by 50% in severe RI [31]. Venlafaxine has been shown to cause hypertension and monitoring of blood pressure is indicated for all patients taking venlafaxine but is especially important for those with pre-existing hypertension [10-11, 31]. Venlafaxine also has an increased bleeding risk and it should be used cautiously in patients with cardiovascular disease [11, 31]. Avoid using the XL preparations if the GFR is <30ml/min [5] Agomelatine is one of the newer antidepressants and there is very little information available regarding its use in RI. Agomelatine is metabolised via the CYP450 pathway to inactive metabolites which are renally excreted [32]. No dosage modification in severe RI is recommended by the manufacturers but caution should be used due to the lack of clinical experience in this patient group [32]. Trazodone is a tricyclic related drug and therefore has cautions similar to the TCAs [11]. Trazodone is extensively metabolised by the CYP450 pathway to active metabolites which are renally excreted [18, 33]. In general doses do not need to be reduced in RI but it is advisable to start with a low dose and increase the dose cautiously [4-5, 33]. Available through NICE Evidence. Search at www.evidence.nhs.uk 3 Medicines Q&As Due to the complexity of using lithium in RI, seek specialist advice before lithium is prescribed. Summary Data on the use of antidepressants in renal impairment are limited. The majority of antidepressants can be used in renal impairment with caution. The choice of the initial antidepressant is based on the same general principles as in normal renal function. Specific increased risks due to renal disease need to be considered. Start with a low dose, titrate slowly and monitor patients closely. Side effects may be enhanced in renal impairment. Extra caution may be needed when switching between antidepressants as half lives may be extended. Lofepramine and duloxetine are contraindicated by their manufacturers in severe renal impairment. Limitations This Medicines Q&A is not designed to be a standalone resource on choice or dosing of antidepressants in renal impairment. Readers are advised to use standard drug dosing in renal disease resources to support decision making. This Q&A is intended for use in adult patients only. The use of antidepressants for indications other than depression is outside the scope of this Q&A. The use of antidepressants in renal replacement therapies is not discussed here. Available through NICE Evidence. Search at www.evidence.nhs.uk 4 Medicines Q&As Table 1: Summary of information on the use of antidepressants in renal impairment from the manufacturer’s product information, Renal Drug Handbook and the Maudsley Prescribing Guidelines. (Details based on current editions and correct at the time of writing). Manufacturers' Information Renal Drug Handbook [4] The Maudsley Prescribing Guidelines [5] Monitor all patients given TCAs for urinary retention, confusion, sedation and postural hypotension. TCAs Amitriptyline No information on dose adjustment available from the manufacturer [20] Clomipramine The effects of RI on the pharmacokinetics of clomipramine have not been determined. [21] Doxepin Use with caution in patients with RI. [22] Imipramine Caution in severe RI. [23] In patients with severe RI, no change occurs in renal excretion of imipramine and its biologically active metabolites. However concentrations of the biologically inactive metabolites are elevated. The clinical significance of this finding is not known. [23] Lofepramine is contraindicated in severe RI. [24] Lofepramine should be used with caution in RI. <10-50 mL/min dose as in normal renal function 10-50 mL/min dose as in normal renal function <10 mL/min start at a low dose 10-50 mL/min dose as in normal renal function <10 mL/min start with a small dose and titrate slowly Nortriptyline No information available from the manufacturer [25] 10-50 mL/min dose as in normal renal function <10 mL/min start with small doses Trimipramine No information available from the manufacturer [26] <10-50 mL/min normal Dosage adjustment is not necessary in mild or moderate RI. [13] No information available for severe RI (CrCl <20 mL / min). [13] Dosage adjustment is not necessary in mild or moderate RI. [14] Caution is advised in patients with severe RI (CrCl <10-50 mL/min dose as in normal renal function Caution <10ml/min, reduced clearance in severe renal failure Dose as for normal renal function. Caution if GFR <10ml/min. 30-50 mL/min dose as in normal renal function <10-30ml/min start with a low dose and titrate slowly Dose as per manufacturer Start with a low dose and increase slowly. Renal failure and reversible renal tubular defects have been Lofepramine <10-50 mL/min dose as in normal renal function Introduce gradually due to dizziness and postural hypotension Withdraw treatment gradually 20-50 mL/min dose as in normal renal function <10-20 mL/min start low and titrate according to response Not included Dose as in normal renal function, but start with a low dose and increase slowly Plasma monitoring may be useful Has been used to treat pain in renal disease 20-50 mL/min dose as in normal renal function <10-20 mL/min, effects unknown, start at a low dose and monitor Dose as in normal renal function Haemolytic anaemia with renal failure has been reported. No specific dose adjustment necessary in RI. Renal impairment and renal damage have been reported rarely. 10-50 mL/min dose as in normal renal function <10 mL/min start at a low dose. Plasma level monitoring recommended at doses >100mg/day. Worsening of GFR in elderly patients has been reported. Dose as for normal renal function. Elevated urea, acute renal failure and interstitial nephritis have been reported. SSRIs Citalopram Escitalopram Available through NICE Evidence. Search at www.evidence.nhs.uk 5 Medicines Q&As Fluoxetine Paroxetine Sertraline <30 mL / min). [14] Dialysis patients given fluoxetine 20mg/day for 2 months, showed no difference in levels of fluoxetine or norfluoxetine compared to controls with no RI. [15] Increased plasma concentrations of paroxetine occur in severe RI (CrCl < 30 mL/min) Therefore, dosage should be restricted to the lower end of the dosage range [16] No dosage adjustment is necessary in patients with RI [17] 10-50ml/min dose as in normal renal function <10 mL/min decrease dose or give alternate days, Metabolites excreted renally, accumulation may occur in severe renal failure 30-50 mL/min dose as in normal renal function <10-30 mL/min start with 20mg, titrate slowly <10-50 mL/min dose as in normal renal function Used in RF at normal doses with caution reported 20-50 mL/min dose as in normal renal function <20 mL/min use a low dose or on alternate days and increase according to response 30-50 mL/min dose as in normal renal function <10-30 mL/min start with 10mg (other sources say start at 20mg) and increase according to response Rarely associated with Fanconi syndrome and acute renal failure. Dosing as for normal renal function Sertraline has been used to treat dialysis-associated hypotension; however acute renal failure has been reported so use with caution. Others Duloxetine No dosage adjustment is necessary for patients with mild or moderate renal dysfunction (CrCl 30 to 80 mL/min). [27] Contraindicated in severe RI (CrCl <30 mL/min). [27] Mirtazapine Clearance of mirtazapine may be decreased in patients with moderate to severe RI (CrCl <40 mL/min). This should be taken into account when prescribing mirtazapine in this category of patients [28] Patients with RI do not require a special dose adjustment of moclobemide [29] Moclobemide Reboxetine Venlafaxine The starting dose with renal insufficiency should be 2mg BD which can be increased based on patients’ tolerance. [30] No change in dosage is necessary for patients with GFR between 30-70 mL/minute, Caution is advised. [31] For patients with severe RI (GFR < 30 mL/min), the dose should be reduced by 50%. [31] Because of inter-individual variability in clearance in these patients, individualisation of dosage may be desirable. [31] 30-50 mL/min dose as in normal renal function, start with a low dose 10-30 mL/min start at a low dose and increase according to response <10 mL/min start at a very low dose and increase according to response 10-50 mL/min dose as in normal renal function <10 mL/min start low, monitor closely As per manufacturer information >30ml/min advise to start at a low dose and increase slowly. <30ml/min contraindicated. <10-50 mL/min dose as in normal renal function <10 -50 mL/min dose as in normal renal function An active metabolite was found to be raised in RI but was not thought to affect dosing. GFR <20ml/min 2mg BD adjust according to response Approximately 10 % is excreted unchanged in the urine Half life is prolonged as renal function decreases Dosing advice differs. 30-50 mL/min dose as in normal renal function or reduce by 50% <10-30 mL/min decrease dose by 50% and give once daily. Avoid using the XL preparations if GFR <30ml/min. Rhabdomyolysis and renal failure have been reported rarely with venlafaxine. Venlafaxine is used to treat neuropathy in dialysis patients. 20-50 mL/min dose as in normal renal function <10-20 mL/min start with 2mg BD and adjust according to response 30-50 mL/min dose as in normal renal function, <10-30 mL/min decrease dose by 50% and administer daily 10-50 mL/min dose as in normal renal function <10 mL/min start low, monitor closely Mirtazapine has been used to treat pruritus caused by renal failure but is associated with kidney calculus formation. Available through NICE Evidence. Search at www.evidence.nhs.uk 6 Medicines Q&As Acknowledgements Highly Specialist Renal Pharmacist, North Bristol NHS Trust Renal Pharmacist, Royal Devon and Exeter NHS Foundation Trust Locality Pharmacists, Avon and Wiltshire Mental Health Partnership NHS Foundation Trust References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. National Institute for Health and Clinical Excellence [NICE]. Depression: the treatment and management of depression in adults (updated edition). National Clinical Practice Guideline 90, 2010. Available from http://www.nice.org.uk/guidance/cg90/evidence/cg90-depression-in-adultsfull-guidance2 Date accessed 29/10/14. National Institute for Health and Clinical Excellence [NICE]. Depression in Adults with a Chronic Physical Health Problem: treatment and management. National Clinical Practice Guideline Number 91, 2009. Available from: http://www.nice.org.uk/guidance/cg91/evidence/cg91depression-with-a-chronic-physical-health-problem-full-guideline2 1 Date accessed 29/10/14 Hedayati SS, Yalamanchili V and Finkelstein FO. A practical approach to the treatment of depression in patients with chronic kidney disease and end-stage renal disease. Kidney Int. 2012 Feb; 81(3):247-255 Ashley C and Dunleavy A. Editors. The Renal Drug Database. Radcliffe Publishing. Available from: www.renaldrugdatabase.com Date accessed: 3/10/14 Monographs last reviewed 18/6/14 Taylor D, Paton C, Kapur S. Use of psychotropics in special patient groups: Renal Impairment. The South London and Maudsley NHS Foundation Trust, Oxleas NHS Foundation Trust (The Maudsley) Prescribing Guidelines 11th Edition. London: Informa Healthcare; 2012; pp462-473. Bazire S. Renal Impairment, Antidepressants. Psychotropic Drug Directory. Aberdeen: HealthComm UK Limited; 2014; pp314-317. Baghdady NT, Banik S, Swartz SA, McIntyre RS. Psychotropic drugs and renal failure: translating the evidence for clinical practice. Adv Ther. 2009 Apr; 26(4):404-24. http://www.ncbi.nlm.nih.gov/pubmed/19444657 Raymond CB, Wazny LDHoncharik PL. Pharmacotherapeutic options for the treatment of depression in patients with chronic kidney disease. Nephrol Nurs J. 2008 May-Jun; 35(3): 257263. http://www.ncbi.nlm.nih.gov/pubmed/18649586 Nagler EV, Webster AC, Vanholder R et al. Antidepressants for depression in stage 3-5 chronic kidney disease: a systematic review of pharmacokinetics, efficacy and safety with recommendations by European Renal Best Practice (ERBP). Nephrol Dial Transplant 2012. 0:110. Advance Access published Aug 1, 2012. Clinical Knowledge Summary. Updated 2013. Depression - Prescribing information. How should I monitor someone taking antidepressants? Accessed via: http://cks.nice.org.uk/depression#!prescribinginfosub:30 Date accessed 29/10/2014 Joint Formulary Committee. British National Formulary. 68th edition.[internet]. Antidepressant Drugs. London: British Medical Association and Royal Pharmaceutical Society; 2014. Accessed via : https://www.medicinescomplete.com/about/publications.htm on 6/11/14 Rayner L, Price A, Evans A, Valsraj K, Higginson IJ, Hotopf M. Antidepressants for depression in physically ill people. Cochrane Database of Systematic Reviews 2010, Issue 3. Art. No.: CD007503. DOI: 10.1002/14651858.CD007503.pub2. Accessed via www.cochrane.org on 6/11/2014 Summary of Product Characteristics. Cipramil Tablets. Lundbeck Ltd. Date of revision of text: 05/6/14. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Cipralex 5, 10 and 20mg film-coated tablets. Lundbeck Ltd. Date of revision of text: 5/9/13. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Prozac 20mg hard capsules, and 20mg/5ml oral liquid. Eli Lilly and Company Ltd. Date of revision of text: 9/10/14. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Available through NICE Evidence. Search at www.evidence.nhs.uk 7 Medicines Q&As 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. Summary of Product Characteristics. Seroxat 10mg, 20mg, 30mg tablets, 20mg/10ml oral suspension. GlaxoSmithKline UK. Date of revision of text: 30/7/14. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of product Characteristics. Lustral. Pfizer Ltd. Date of revision of text: 10/2014. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. DRUGDEX System: Drugdex Drug Evaluations amitriptyline, clomipramine, doxepin, imipramine lofepramine nortriptyline, trimipramine, citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, mirtazapine, moclobemide, reboxetine, venlafaxine, trazodone. monographs. In: DRUGDEX System (electronic version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at http://www.micromedexsolutions.com/home/dispatch Accessed 29/9/14 Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). http://medicine.iupui.edu/clinpharm/ddis/main-table/ Date accessed: 25/9/2014 Summary of Product Characteristics. Amitriptyline tablets 10mg. Accord Healthcare. Date of revision of text: 2/3/12. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Anafranil 75mg SR Tablets. Novartis Pharmaceuticals UK Ltd. Date of revision of text 11/6/14. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Sinepin Capsules 50mg. Marlborough Pharmaceuticals Ltd. Date of revision of text: 22/1/14. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/2014. Summary of Product Characteristics. Imipramine tablets 25mg. Actavis UK. Date of revision of text: 4/6/14. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Lofepramine 70mg Tablets (Arrow). Actavis UK. Date of revision of text: 27/3/14. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Nortriptyline. King Pharmaceuticals Ltd. Date of revision of text: Nov 2010. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Trimipramine Capsules 50mg. Zentiva. Date of revision of text: 20/09/12. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Cymbalta 30mg hard gastro-resistant capsules, Cymbalta 60mg hard gastro-resistant capsules. Eli Lilly and Company Ltd. Date of revision of text: 26/6/14. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics Mirtazapine 30mg tablets. Sandoz. Date of revision of text: 3/14. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Manerix 150mg. Meda Pharmaceuticals. Date of revision of text: 11/13. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Edronax 4mg tablets, Pfizer UK. Date of revision of text: 7/2013. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Efexor XL 150mg hard prolonged release capsules. Pfizer UK. Date of revision of text: Dec 2013. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Valdoxan. Servier Laboratories Ltd. Date of revision of text: 11/14. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Summary of Product Characteristics. Molipaxin 150mg Tablets. Sanofi-Aventis. Date of revision of text: 22/8/13. Accessed via: http://emc.medicines.org.uk. Date accessed: 25/9/14. Quality Assurance Prepared by Tiffany Barrett, based on earlier work by Nicola Greenhalgh, South West Medicines Information, University Hospitals Bristol NHS Foundation Trust Date Prepared October 2014 Available through NICE Evidence. Search at www.evidence.nhs.uk 8 Medicines Q&As Checked by Julia Kuczynska, South West Medicines Information, University Hospitals Bristol NHS Foundation Trust Date of check December 2014 Search strategy Embase (via NHS Evidence) - Search terms used: exp ANTIDEPRESSANT AGENT and (exp KIDNEY DYSFUNCTION OR exp KIDNEY DISEASE or KIDNEY FAILURE) Limit to: Human and English Language and Publication Year 2011-Current and (Human Age Groups Adult 18 to 64 years or Aged 65+ years Medline (via NHS Evidence) – Search terms used: (exp ANTIDEPRESSIVE AGENTS or exp DEPRESSIVE DISORDER) and (exp RENAL INSUFFICIENCY or exp KIDNEY DISEASES or exp ACUTE KIDNEY INJURY) [Limit to: English Language and Humans and Publication Year 2011-Current and (Age Groups Adult 19 to 44 years or Middle Age 45 to 64 years or Middle Aged 45 plus years or All Aged 65 and Over or Aged 80 and Over)];. In-house database/ resources The Renal Association: http://www.renal.org/home.aspx The Royal College of Psychiatrists: http://www.rcpsych.ac.uk/ Available through NICE Evidence. Search at www.evidence.nhs.uk 9