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Choosing the Right Antidepressant for Depression: Individual Patient Data Network Meta-Analysis








Choosing the Right Antidepressant for Depression: Individual Patient Data Network Meta-Analysis


Professor Andrea Cipriani


Department of Psychiatry, University of Oxford     Oxford Health NHS Foundation Trust






10 December 2019


1.1.   BackgroundDepression is a very common major health problem. With 350 million people affected in the world, depressive disorder is the second leading cause of global burden.1 The high direct and indirect costs for major depression are largely due to significant problems in treatment.2 There are several effective treatments for depressive disorder, but the key challenge is how best to use and deliver currently available effective treatments.3International guidelines recommend antidepressant drugs as first line treatment for adults with moderate to severe depression.4 In England alone, 64.7m prescriptions of antidepressants were dispensed in 2016, more than twice the 31m antidepressants dispensed in 2006. Many patients, however, are given antidepressants, which, for them, prove ineffective or cause intolerable side-effects. This happens because antidepressants are prescribed without a clear understanding of which drug is the most appropriate medication for each patient in terms of both efficacy (effectiveness of treatment to reduce symptoms) and tolerability (the degree to which the side effects can be tolerated by a patient). The majority of prescriptions are for less than 30 days,5 while an adequate trial of antidepressants is generally recommended to be 6-8 weeks before changing or stopping the medication. A too short duration of treatment both limits the therapeutic effect6 and increases the risk of withdrawal symptoms because antidepressants should be tapered off over a period of 4 weeks.5 This can result in patients stopping the antidepressant early because they are prescribed a drug which might work for the “average person” but has not been tailored to them individually.1.2.   Aim We aim to ultimately develop and test an evidence-based clinical decision support tool to personalise treatment in depression in the UK. We already have the knowledge which can markedly reduce these shortcomings in using the right antidepressant in treating depression. Implementing a careful analysis of existing data on antidepressants, we can better tailor the choice of a specific drug to a specific person, to increase the likelihood that the drug will be tolerable and effective. The overall aim of this project is to develop an internet-based system, which will help doctors, and patients together choose the best antidepressant for each individual with moderate to severe symptoms of depression, considering together both the efficacy and the adverse events of these drugs. This project specially aims to develop and test a novel precision medicine approach to the optimise the medical (drug) treatment of depressive disorder, which can be used in everyday clinical settings. We aim to develop a web-based platform using large and diverse datasets combining data from hundreds of thousands of patients, to inform shared decision-making at the individual patient level during the routine consultation between doctors and patients. The first phase of this project is obtaining individual patient data which will form a vital part of the dataset. 1.3.   Objectives The main objectives of this project are to:1.   Collect and summarise the best and most up-to-date scientific evidence about the effectiveness and side effects of antidepressants for major depression in adults and produce treatment recommendations;72.   Produce a tool to combine these recommendations with information from electronic patient records and clinicians and patients' preferences, to tailor treatments to individual patients;3.   Test whether use of the tool in real-world clinical settings helps patients to follow and keep to treatment, is acceptable to clinicians and patients and is economically feasible.



[{ "PostingID": 1617, "Title": "GSK-29060/785", "Description": "A double-blind, placebo-controlled, fixed-dosage study comparing the efficacy and tolerability of paroxetine CR and citalopram to placebo in the treatment of Major Depressive Disorder with anxiety" },{ "PostingID": 1623, "Title": "GSK-MY-1043/BRL-029060/115", "Description": "A multicenter, randomized, double-blind, placebo-controlled comparison of paroxetine and fluoxetine in the treatment of major depressive disorder." },{ "PostingID": 1633, "Title": "GSK-29060/448", "Description": "A Double-Blind, Placebo Controlled Trial to Evaluate the Clinical Effects of Immediate Release Paroxetine and Modified Release Paroxetine in the Treatment of Major Depression" },{ "PostingID": 1634, "Title": "GSK-29060/449", "Description": "A Double-Blind, Placebo Controlled Trial to Evaluate the Clinical Effects of Immediate Release Paroxetine and Modified Release Paroxetine in the Treatment of Major Depression" },{ "PostingID": 1638, "Title": "GSK-29060/810", "Description": "A double-blind, placebo-controlled, 3-arm, fixed-dose study of 12.5 mg/day and 25mg/day Paroxetine CR in the treatment of Major Depression." },{ "PostingID": 1639, "Title": "GSK-29060/874", "Description": "Assessment of Paxil CR, 12.5 and 25 mg/day in treating elderly patients with major depression" },{ "PostingID": 2063, "Title": "GSK-AK130939", "Description": "A Multi-Centre, Randomised, Double-Blind, Parallel-Group, Placebo- and Active-Controlled, Flexible Dose Study Evaluating the Efficacy, Safety and Tolerability of Extended-Release Bupropion Hydrochloride (150mg - 300mg once daily), Extended-Release Venlafaxine Hydrochloride (75mg - 150mg once daily) and Placebo in Subjects with Major Depressive Disorder." },{ "PostingID": 2064, "Title": "GSK-WXL101497", "Description": "A Multi-Centre, Randomised, Double-Blind, Parallel-Group, Placebo- and Active-Controlled, Flexible Dose Study Evaluating the Efficacy, Safety and Tolerability of Extended-Release Bupropion Hydrochloride (150mg - 300mg once daily), Extended-Release Venlafaxine Hydrochloride (75mg - 150mg once daily) and Placebo in Subjects with Major Depressive Disorder." },{ "PostingID": 2122, "Title": "GSK-29060/01/001", "Description": "A Phase II, Placebo-Controlled, Double-Blind Study of Paroxetine in Depressed Outpatients" },{ "PostingID": 2123, "Title": "GSK-29060/02/001", "Description": "A Double-Blind, Placebo-Controlled Study of Paroxetine in Depressed Outpatients" },{ "PostingID": 2124, "Title": "GSK-29060/03/001", "Description": "A Double-Blind, Imipramine- and Placebo-Controlled Study of Paroxetine in Depressed Outpatients" },{ "PostingID": 2125, "Title": "GSK-29060/07/001", "Description": "A Double-Blind Comparison of Paroxetine, Amitriptyline, and Placebo in Inpatients with Major Depressive Disorder with Melancholia" },{ "PostingID": 2126, "Title": "GSK-29060/009", "Description": "A Multicenter, Double-blind, Placebo-controlled Fixed-dose Evaluation of Four Doses of Paroxetine" },{ "PostingID": 2129, "Title": "GSK-29060/128", "Description": "A Multicenter, Randomized, Double-Blind, Placebo-Controlled Comparison of Paroxetine and Fluoxetine in the Treatment of Major Depressive Disorder" },{ "PostingID": 2130, "Title": "GSK-29060/251", "Description": "A Double-Blind, Randomized Trial of Paroxetine Versus Placebo In Patients With Depression Accompanied by Anxiety" },{ "PostingID": 2132, "Title": "GSK-26090/007", "Description": "A Double-Blind Placebo Controlled Study to Compare Paroxetine with Maprotiline in the Treatment of Depression" },{ "PostingID": 2133, "Title": "GSK-29060/276", "Description": "A double-blind study to investigate the efficacy, safety and tolerability of Paroxetine in the treatment of depression in comparison with placebo" },{ "PostingID": 2134, "Title": "GSK-29060/012_3", "Description": "A Study to Assess the Effectiveness and Tolerance of Paroxetine by Double-Blind Comparison with Placebo and Mianserin" },{ "PostingID": 2137, "Title": "GSK-29060/487", "Description": "A Double-Blind, Placebo Controlled Trial to Evaluate the Clinical Effects of Immediate Release Paroxetine and Controlled Release Paroxetine in the Treatment of Major Depression in Elderly Patients" },{ "PostingID": 3705, "Title": "GSK-AK1113351", "Description": "Study AK1113351, a fixed dose study of 323U66 SR in the treatment of Major Depressive Disorder (MDD) - a multi-center, placebo-controlled, randomized, double-blind, parallel-comparison study" },{ "PostingID": 4238, "Title": "GSK-PCR112810", "Description": "A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Clinical Effects of Controlled Release Paroxetine in the Treatment of Major Depressive Disorder" },{ "PostingID": 4919, "Title": "GSK-29060/274", "Description": "A study to assess the effectiveness and tolerance of paroxetine by double-blind comparison with placebo" },{ "PostingID": 20065, "Title": "GSK-PAR 29060.308 (HP/81/74A)", "Description": "Early clinical evaluation of a new antidepressant: A double-blind parallel study comparing paroxetine 30mg daily with amitriptyline 150mg daily" },{ "PostingID": 20066, "Title": "GSK-PAR 29060.309 HP/81/162A", "Description": "Early Clinical Evaluation of a New Antidepressant: A Double-Blind Parallel Study Comparing Paroxetine 30mg Daily with Amitriptyline 100mg Daily" },{ "PostingID": 20067, "Title": "GSK-PAR 29060.310 (HP 81/85A)", "Description": "Early Clinical Evaluation of a New Antidepressant: Double-Blind Parallel Study Comparing Paroxetine 30mg Daily with Amitriptyline 150mg Daily" },{ "PostingID": 20068, "Title": "GSK-PAR 29060.316 (HP/82/47A)", "Description": "Early Clinical Evaluation of a New Antidepressant: A Double-Blind Parallel Study Comparing Paroxetine 30mg Daily with Amitriptyline 150mg Daily" },{ "PostingID": 20069, "Title": "GSK-PAR 29060.314 (HP 82/134)", "Description": "Double Blind Parallel Study Comparing Paroxetine, 30mg Daily, and Amitriptyline, 150mg Daily, in Depressed Patients" },{ "PostingID": 20070, "Title": "GSK-PAR 29060/281", "Description": "A trial to assess the effectiveness and tolerance of paroxetine by double-blind comparison with amitriptyline in the treatment of depressed patients in General Practice" },{ "PostingID": 20071, "Title": "GSK-PAR 290 MDF 29060 1727 M", "Description": "A prospective, randomized, double-blind, multicentre study of the efficacy and tolerance of paroxetine versus clomipramine in the treatment of endogenous depression in the elderly" },{ "PostingID": 20072, "Title": "GSK-PAR MDED/29060/III/86/1728M291", "Description": "A Multi-Centre Double-Blind Study to Investigate the Safety and Efficacy of Paroxetine in Comparison with Clomipramine in the Treatment of Reactive Depression in Elderly Patients." },{ "PostingID": 20073, "Title": "GSK-MDF/29060/III/070/88/MC", "Description": "A multicentre, double-blind, parallel group, randomised dose study comparing the efficacy of paroxetine 20mg increasing to 30mg daily if there is insufficient response and clomipramine 60mg increasing to 75mg daily, in outpatients (age >60 years) with moderate depression according to feighner's criteria" },{ "PostingID": 20074, "Title": "GSK-MY-1001/BRL-029060/1/CPMS 069", "Description": "A Multicentre, Parallel Group Study to Compare the Efficacy and Tolerability of Paroxetine with Clomipramine in Elderly Patients." },{ "PostingID": 20075, "Title": "GSK-MY-060/BRL-029060/1.", "Description": "A multicentre, double-blind, randomised dose titration study comparing the pharmacodynamics and pharmacokinetics of paroxetine 20mg increasing to 30mg daily and amitriptyline 100mg increasing to 150mg daily in geriatric patients (age >65 years) with major depression." },{ "PostingID": 20076, "Title": "GSK-MY 1021/BRL 029060/1/CPMS/061", "Description": "A Double-blind Comparative Study Comparing Paroxetine b.d. (twice daily) with Fluoxetine b.d. (twice daily) in Geriatric Patients with Major Depression" },{ "PostingID": 20077, "Title": "GSK-PAR 29060/078", "Description": "A Multicentre Double Blind Study Comparing Paroxetine at a Dose of 20mg Increasing to 30mg Taken in the Morning and Amitriptyline 75mg Increasing to 150mg in Divided Doses in Adult Patients with Major Depressive Disorder" },{ "PostingID": 20078, "Title": "GSK-29060/063", "Description": "A double blind randomised trial comparing the effects on sleep of paroxetine 30mg daily and amitriptyline 150mg daily in patients with major depression." },{ "PostingID": 20079, "Title": "GSK-MY-1005/BRL-029060/1/CPMS-112", "Description": "A double-blind, multicentre study to compare the effectiveness and tolerance of paroxetine versus fluvoxamine in depressed patients" },{ "PostingID": 20080, "Title": "GSK-29060/064", "Description": "A Double-blind Comparative Multicentre Study Comparing Paroxetine b.d. (twice daily) with Fluoxetine b.d. (twice daily) in Depressed Patients" },{ "PostingID": 20081, "Title": "GSK-MY-1010/BRL029060/1/CPMS 079", "Description": "A double-blind comparative multicentre study comparing paroxetine b.d. (twice daily) with fluoxetine (ProzacĀ®) b.d. (twice daily) in depressed patients" },{ "PostingID": 20082, "Title": "GSK-MY-059.073/29060/1", "Description": "A Multicentre, Double-blind Randomised Dose Titration Study Comparing the Efficacy and Safety Profiles of an Increasing Dose Regimen of Oral Paroxetine and Oral Amitriptyline in Adult Patients with Major Depression" },{ "PostingID": 20083, "Title": "GSK-MY-1055/BRL-029060/1/CPMS-245 PAR 245", "Description": "A Double-Blind, Multicentre Study in Primary Care Comparing Paroxetine and Clomipramine in Patients with Depression with Associated Anxiety" },{ "PostingID": 20084, "Title": "GSK-29060/131", "Description": "A Double-Blind, Randomized, Multicentre Comparison of Paroxetine and Fluoxetine in the Treatment of Patients With Major Depression With Regard to Antidepressant Efficacy, Tolerance and Anxiolytic Effect" },{ "PostingID": 20085, "Title": "GSK-MY-1008/BRL-029060/2/CPMS-076", "Description": "The Effects of Paroxetine Versus Those of Maprotiline and Placebo on Fundamental Cognitive Functions, Perceptual-Motor Skills and Eye Movements in Depressed Patients" },{ "PostingID": 20086, "Title": "GSK-88", "Description": "Double-Blind Comparison of Bupropion and Fluoxetine in Depressed Outpatients" },{ "PostingID": 20087, "Title": "GSK-89", "Description": "Six-week, parallel, double-blind, randomized comparison of bupropion and trazodone (150-400mg/day) in outpatients" },{ "PostingID": 20088, "Title": "GSK-WELL 203", "Description": "A Multicenter Evaluation of the Safety and Efficacy of 150mg/day and 300mg/day of Bupropion HCl Sustained-Release Versus Placebo in Depressed Outpatients" },{ "PostingID": 20089, "Title": "GSK-Well 209", "Description": "The Safety and Efficacy of Wellbutrin Sustained Release and Sertraline in Depressed Outpatients" },{ "PostingID": 20090, "Title": "GSK-WELL 212", "Description": "A multicenter evaluation of the safety and efficacy of two flexible doses of WELLBUTRIN sustained-release versus placebo in depressed outpatients" },{ "PostingID": 20091, "Title": "GSK-WELL AK1A4002", "Description": "A Multicenter, Double-Blind, Placebo-Controlled Comparison of the Effects on Sexual Functioning of Wellbutrin (Bupropion HCl) Sustained Release and Sertraline in Outpatients with Moderate to Severe Recurrent Major Depression" },{ "PostingID": 20092, "Title": "GSK-WELL AK1A4001", "Description": "A Multicenter, Double-Blind, Placebo-Controlled Comparison of the Effects on Sexual Functioning of Wellbutrin (Bupropion HCI) Sustained Release and Sertraline in Outpatients with Moderate to Severe Recurrent Major Depression" },{ "PostingID": 20093, "Title": "GSK-WELL AK1A4007", "Description": "A Multicenter, Double-Blind, Placebo-Controlled Comparison of the Safety and Efficacy and Effects on Sexual Functioning of Wellbutrin (Bupropion HCl) Sustained Release (SR) and Fluoxetine in Outpatients with Moderate to Severe Recurrent Major Depression" },{ "PostingID": 20094, "Title": "GSK-WELL 205", "Description": "A multicenter dose-response evaluation of the safety and efficacy of bupropion HCI sustained-release versus placebo in depressed outpatients" },{ "PostingID": 20095, "Title": "GSK-WELL AK1A4006", "Description": "A Multicenter, Double-Blind, Placebo-Controlled Comparison of the Safety and Efficacy and Effects on Sexual Functioning of Wellbutrin (Bupropion HCl) Sustained Release (SR) and Fluoxetine in Outpatients with Moderate to Severe Recurrent Major Depression" },{ "PostingID": 20096, "Title": "GSK-AK1102365", "Description": "Clinical evaluation of 323U66 SR in patients with depression - Placebo-controlled, double-blind, comparative study in patients with depression who did not respond sufficiently to selective serotonin re-uptake inhibitors" }]

Statistical Analysis Plan