Monitoring for antidepressant-associated adverse events in the treatment of patients with major depressive disorder: An international consensus statement

Abstract

Objectives: These recommendations were designed to ensure safety for patients with major depressive disorder (MDD) and to aid monitoring and management of adverse effects during treatment with approved antidepressant medications. The recommendations aim to inform prescribers about both the risks associated with these treatments and approaches for mitigating such risks.

Methods: Expert contributors were sought internationally by contacting representatives of key stakeholder professional societies in the treatment of MDD (ASBDD, CANMAT, WFSBP and ISAD). The manuscript was drafted through iterative editing to ensure consensus.

Results: Adequate risk assessment prior to commencing pharmacotherapy, and safety monitoring during pharmacotherapy are essential to mitigate adverse events, optimise the benefits of treatment, and detect and assess adverse events when they occur. Risk factors for pharmacotherapy vary with individual patient characteristics and medication regimens. Risk factors for each patient need to be carefully assessed prior to initiating pharmacotherapy, and appropriate individualised treatment choices need to be selected. Some antidepressants are associated with specific safety concerns which were addressed.

Conclusions: Risks of adverse outcomes with antidepressant treatment can be managed through appropriate assessment and monitoring to improve the risk benefit ratio and improve clinical outcomes.

Keywords:

• Antidepressants
• adverse effects
• major depressive disorder
• evidence-based guidelines
• pharmacotherapy

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Corrigendum

Acknowledgements

None.

Statement of interest

The authors wish to declare the following conflicts of interest. Dr Dodd has received research support from Stanley Medical Research Institute, NHMRC, Beyond Blue, ARHRF, BioAdvantex, Simons Foundation, Geelong Medical Research Foundation, Fondation FondaMental, Eli Lilly, Glaxo SmithKline, Organon, Mayne Pharma and Servier, speaker’s fees from Eli Lilly, advisory board fees from Eli Lilly and Novartis and conference travel support from Servier. Dr Bauer has received research support from Bundesministerium für Bildung und Forschung (BMBF), honoraria from AstraZeneca, Ferrer Internacional, Lilly, Lundbeck, Otsuka, Pfizer and Servier, and has been a speaker or advisory board member for Allergan, Ferrer Internacional, Janssen, Lilly, Lundbeck, Neurapharm, Otsuka, and Servier. Dr Yatham has been on speaker/advisory boards for, or has received research support from Alkermes, AstraZeneca, CANMAT, CIHR, Dainippon Sumitomo Pharma, Lundbeck, Otsuka, Servier, Sunovion and Teve. Dr Young has been on speaker/advisory boards for AstraZeneca, Eli Lilly, Janssen, Lundbeck, Sunovion, Livanova Servier, and has received research support from NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK). He has been a Lead Investigator for Embolden Study (AZ), BCI Neuroplasticity study and Aripiprazole Mania Study and has conducted Investigator initiated studies from AZ, Eli Lilly, Lundbeck, Wyeth. SHK has received research funding or honoraria from Allergan, AstraZeneca, BMS, Brain Canada, Canadian Institutes for Health Research (CIHR), Eli Lilly, Janssen, Lundbeck, Lundbeck Institute, OMHF, Ontario Brain Institute, Ontario Research Fund (ORF), Pfizer, Servier, St. Jude Medical, Sunovion and Xian-Janssen. Dr Suppes has been on speaker/advisory boards for, or has received research support from Jones and Bartlett, NIMH, VA, CSP, Pathway Genomics, Stanley Medical Research Institute, Elan Pharma International, Sunovion, Global Medication Education, CMEology, Merck, Lundbeck. Dr Trivedi has been on speaker/advisory boards for, or has received research support from the Agency for Healthcare Reseacrh and Quality, Cyberonics Inc, National Alliance for Research in Schizophrenia and Depression, NIMH, NIDA, NIDDK, Johnson & Johnson, Abbott, Akzo, Allergan, Alkermes, Arcadia, AstraZenecea, Axon Advisors, Brintellix, BMS, Cephalon, Cerecor, Eli Lilly, Evotec, Fabre Kramer, Forest, GSK, Global Medical Education, Health Research Associates, Lundbeck, MedAvante, Medscape, Medtronic, Merck, Mitsubishi Tanabe, MSI Methylation Sciences, Nestle Health Science – PamLab, Naurex, Neuronetics, One Carbon Therapeutics, Otsuka, Parke-Davis, Pfizer, PgxHealth, Phoenix Marketing Solutions, Rexahn, Ridge Diagnostics, Roche, Sepracor, SHIRE Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Trancept, VantagePoint, Vivus, and Wyeth-Ayerst, and has received royalties from Janssen. Dr Fava has been on speaker/advisory boards for, or has received research support from Abbott, Adamed, Advanced Meeting Partners, Arcadia, Affectis, AstraZenecea, Alkermes, Amarin, American Psychairic Association, American Society of Clinical Psychopharmacology, American Cyanamid, Aspect Medical Systems, Auspex, Avanir, AXSOME Therapeutics, Bayer, Belvoir Media Group, Best Practice Project Management, Biogen, BioMarin, Biovail, BioResearch, BrainCells, BMS, CeNeRx BioPharma, Beohringer-Ingelheim, Cephalon, Cerecor, CME Institute, CNS response, Compellis, Cypress, DiagnoSearch Life Sciences, Covance, Covidien, Dinippon Sumitomo, Dov, Edgemont, Eli Lilly, Eisai, ePharmasolutions, EPIX, EnVivo, Euthymics Bioscience, Fabre-Kramer, Forest, FORUM, GenOmind, Ganeden Biotech, GSK, Grunenthal, Harvard Clinical Research Institute, Hoffman-LaRoche, Icon Clinical Research, Imedex, i3Innovus/Ingenix, Indivior, Intracellular, Janssen, Jed Foundation, Jazz, Johnson & Johnson, Knoll, Labopharm, Lichtwer, Lorex, Lundbeck, Marinus, MedAvante, Merck, Methylation Sciences, MGH Psychiatry Academy, NARSAD, NCCAM, NiiCM, NIDA, NIMH, Neuralstem, NeuroRx, Novartis, Naurex, Nestle Health Sciences, Neuronetics, NextWave, Nutrition 21, Orexigen, Osmotica Organon, PamLab, Otsuka, Pfizer, Pharmacia-Upjohn, Pharmaceutical Research Associates, Pharmastar, Precision Human Biobaloratory, Prexa, PPD, Puretech Ventures, Pharmavite, PhamoRx, Photothera, PsychoGenics, Psylin Neurosciences, Reckitt Benckiser, Roche, RCT logic, Rexahn, Ridge Diagnostics, Sanofic-Adventis, Sepracor, Servier, Schering-Plough, Shenox, Somaxon, Somerset, Sunovoin, Supernus, Shire, Solvay, Stanley MRI, Synthelabo, Taisho, Takeda, Tal Medical, Tetragenex, Teva, TransForm, Transcept, United BioSource, Vanda, VistaGen, Wyeth-Ayerst, equity holdings with Compellis and PsyBrain, patents for SPCD and depression treatment with folate, a patent application for ketamine plus scopolamine for MDD and holds copyright for the CPFQ, SFI, ATRQ, DESS, SDQ and SAFER. Dr Rush has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: Asia-Pacific Economic Cooperation, AstraZeneca, BC Leading Edge Foundation, Brain Canada, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Janssen, Lundbeck, Lundbeck Institute, Medscape, Pfizer, St. Jude Medical, Takeda, University Health Network Foundation, Vancouver Coastal Health Research Institute, and VGH Foundation. Dr McIntyre has received grant/speaker fees from Lundbeck, Otsuka, Pfizer, Shire, Purdue, Takeda, Allergan, Bristol-Myers Squibb, AstraZeneca, Eli Lilly, Janssen Ortho. Dr Thase has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: Acadia, Alkermes, Allergan (Forest, Naurex), AstraZeneca, Cerecor, Eli Lilly, Fabre-Kramer Pharmaceuticals, Inc., Gerson Lehrman Group, Guidepoint Global, Johnson & Johnson (Janssen, Ortho-McNeil), Lundbeck, MedAvante, Inc., Merck, Moksha8, Nestlé (PamLab), Novartis, Otsuka, Pfizer, Shire, Sunovion, Takeda, Agency for Healthcare Research and Quality, AssureRx, Avanir, Forest Pharmaceuticals, Janssen, Intracellular, National Institute of Mental Health, Otsuka Pharmaceuticals, has equity holdings in MedAvante, receives royalties from the American Psychiatric Foundation, Guilford Publications, Herald House, and W.W. Norton & Company, and his spouse is employed by Peloton Advantage. Dr Lam has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: AstraZeneca, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Lundbeck, Lundbeck Institute, Otsuka, Allergan, Asia-Pacific Economic Cooperation, Bristol Myers Squibb, Canadian Depression Research and Intervention Network, Janssen, Medscape, Pfizer, Takeda, BC Leading Edge Foundation, Brain Canada, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Movember Foundation, St. Jude Medical, University Health Network Foundation, Vancouver Coastal Health Research Institute, VGH Foundation, hold a copyright for the Lam Employment Absence and Productivity Scale (LEAPS) and receives royalties from Cambridge University Press, Informa Press, Oxford University Press. Dr Severus has received honoraria for ad hoc speaking or advising/consulting from Servier and Lunbeck. Dr Kasper has within the last three years received honoraria for advising/consulting or research funds from Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre, Schwabe and Servier. Dr Berk has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: Stanley Medical Research Foundation, MBF, NHMRC, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, MBF, Rotary Health, Meat and Livestock Board, Woolworths, BeyondBlue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis, Mayne Pharma, Servier, Astra Zeneca, Lundbeck, Pfizer, Sanofi Synthelabo, and is a co-inventor of two provisional patents regarding the use of NAC and related compounds for psychiatric indications, which, while assigned to the Mental Health Research Institute, could lead to personal remuneration upon a commercialisation event.

Dr Berk is supported by a NHMRC Senior Principal Research Fellowship (1059660). Dr Williams is supported by a NHMRC Career Development Fellowship (1064272).