• Maike Scherf-ClavelEmail author
Living reference work entry


Fatal outcomes related to the use of drugs in the past, for example, most prominently, the thalidomide tragedy, has caused the development of systematic, structured and regulated pharmacovigilance system in the 1960s. Pharmacovigilance includes processes for monitoring and evaluating adverse drug effects with the aim to improve the safety of a drug therapy. Core functions of pharmacovigilance are case management, signal management, and benefit-risk management. They cover the early stages in a drug’s life cycle, but also, as it is impossible to identify all safety concerns during clinical trials, post-marketing observational analyses. In later stages of a drug’s life cycle safety monitoring is based on spontaneous reporting of ADEs. In the EU and the USA, good pharmacovigilance systems are established; however, in some middle- and low-income countries, pharmacovigilance is still at its beginning or not available.

This chapter focusses on pharmacovigilance, describing how it works, what methods are used, describing more or less advanced pharmacovigilance systems in different countries, what an adverse drug effect and an adverse drug event is, and how to prevent and to manage adverse drug effects, especially in the field of neuropsychopharmacology.


  1. Ables AZ, Nagubilli R. Prevention, recognition, and management of serotonin syndrome. Am Fam Physician. 2010;81:1139–42.PubMedGoogle Scholar
  2. Alshammari TM, Mendi N, Alenzi KA, Alsowaida Y. Pharmacovigilance systems in Arab countries: overview of 22 Arab countries. Drug Saf. 2019;42:849–68.PubMedCrossRefGoogle Scholar
  3. Awada Z, Zgheib NK. Pharmacogenovigilance: a pharmacogenomics pharmacovigilance program. Pharmacogenomics. 2014;15:845–56.PubMedCrossRefGoogle Scholar
  4. Baumann P. Pharmacovigilance in psychiatry: pharmacogenetic tests and therapeutic drug monitoring are promising tools. Expert Rev Clin Pharmacol. 2008;1:183–5.PubMedCrossRefGoogle Scholar
  5. Beninger P. Pharmacovigilance: an overview. Clin Ther. 2018;40:1991–2004.PubMedCrossRefGoogle Scholar
  6. Bigi C, Bocci G. The key role of clinical and community health nurses in pharmacovigilance. Eur J Clin Pharmacol. 2017;73:1379–87.PubMedCrossRefGoogle Scholar
  7. Biswas P. Pharmacovigilance in Asia. J Pharmacol Pharmacother. 2013;4:S7–s19.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Brandl EJ, Kennedy JL, Muller DJ. Pharmacogenetics of antipsychotics. Can J Psychiatr. 2014;59:76–88.CrossRefGoogle Scholar
  9. Brouillette J, Nattel S. A practical approach to avoiding cardiovascular adverse effects of psychoactive medications. Can J Cardiol. 2017;33:1577–86.PubMedCrossRefGoogle Scholar
  10. Cantudo Cuenca M, Munoz Cejudo B, Mora Mora M, Fernandez Martinez G, Cantal Sanchez M. Applying different scales for calculating the anticholinergic burden in older patients. European Association of Hospital Pharmacists. Accessed 16 Dec 2019.
  11. Coleman JJ, Pontefract SK. Adverse drug reactions. Clin Med (Lond). 2016;16:481–5.CrossRefGoogle Scholar
  12. Collamati A, Martone AM, Poscia A, Brandi V, Celi M, Marzetti E, Cherubini A, Landi F. Anticholinergic drugs and negative outcomes in the older population: from biological plausibility to clinical evidence. Aging Clin Exp Res. 2016;28:25–35.PubMedCrossRefGoogle Scholar
  13. Dean L. Clozapine therapy and CYP2D6, CYP1A2, and CYP3A4 genotypes. In: Pratt V, McLeod H, Rubinstein W, Dean L, Kattman B, Malheiro A, editors. Medical genetics summaries. Bethesda: National Center for Biotechnology Information (US); 2012.Google Scholar
  14. Dodd S, Mitchell PB, Bauer M, Yatham L, Young AH, Kennedy SH, Williams L, Suppes T, Lopez Jaramillo C, Trivedi MH, Fava M, Rush AJ, McIntyre RS, Thase ME, Lam RW, Severus E, Kasper S, Berk M. Monitoring for antidepressant-associated adverse events in the treatment of patients with major depressive disorder: an international consensus statement. World J Biol Psychiatry. 2018;19:330–48.PubMedCrossRefGoogle Scholar
  15. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet. 2000;356:1255–9.PubMedCrossRefGoogle Scholar
  16. FDA. Guidance for industry – good pharmacovigilance practices and pharmacoepidemiologic assessment. Food and Drug Administration. 2005. Accessed 21 Nov 2019.
  17. Fornasier G, Francescon S, Leone R, Baldo P. An historical overview over pharmacovigilance. Int J Clin Pharm. 2018;40:744–7.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Gaitatzis A, Sander JW. The long-term safety of antiepileptic drugs. CNS Drugs. 2013;27:435–55.PubMedCrossRefGoogle Scholar
  19. Garon SL, Pavlos RK, White KD, Brown NJ, Stone CA Jr, Phillips EJ. Pharmacogenomics of off-target adverse drug reactions. Br J Clin Pharmacol. 2017;83:1896–911.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Gentry CA, Rodvold KA. How important is therapeutic drug monitoring in the prediction and avoidance of adverse reactions? Drug Saf. 1995;12:359–63.PubMedCrossRefGoogle Scholar
  21. Gerlach M, Egberts K, Dang SY, Plener P, Taurines R, Mehler-Wex C, Romanos M. Therapeutic drug monitoring as a measure of proactive pharmacovigilance in child and adolescent psychiatry. Expert Opin Drug Saf. 2016;15:1477–82.PubMedCrossRefGoogle Scholar
  22. Guerrini R, Perucca E. Genetic testing to prevent adverse reactions to antiepileptic drugs: Primum non nocere. Neurology. 2018;90:155–6.PubMedCrossRefGoogle Scholar
  23. Hadi MA, Neoh CF, Zin RM, Elrggal ME, Cheema E. Pharmacovigilance: pharmacists' perspective on spontaneous adverse drug reaction reporting. Int Pharm Res Pract. 2017;6:91–8.Google Scholar
  24. Haen E. Therapeutic drug monitoring in pharmacovigilance and pharmacotherapy safety. Pharmacopsychiatry. 2011;44:254–8.PubMedCrossRefGoogle Scholar
  25. Harmark L, van Grootheest AC. Pharmacovigilance: methods, recent developments and future perspectives. Eur J Clin Pharmacol. 2008;64:743–52.PubMedCrossRefGoogle Scholar
  26. Hiemke C, Bergemann N, Clement HW, Conca A, Deckert J, Domschke K, Eckermann G, Egberts K, Gerlach M, Greiner C, Grunder G, Haen E, Havemann-Reinecke U, Hefner G, Helmer R, Janssen G, Jaquenoud E, Laux G, Messer T, Mossner R, Muller MJ, Paulzen M, Pfuhlmann B, Riederer P, Saria A, Schoppek B, Schoretsanitis G, Schwarz M, Gracia MS, Stegmann B, Steimer W, Stingl JC, Uhr M, Ulrich S, Unterecker S, Waschgler R, Zernig G, Zurek G, Baumann P. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017. Pharmacopsychiatry. 2018;51:9–62.PubMedCrossRefGoogle Scholar
  27. Huhn M, Nikolakopoulou A, Schneider-Thoma J, Krause M, Samara M, Peter N, Arndt T, Backers L, Rothe P, Cipriani A, Davis J, Salanti G, Leucht S. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet. 2019;394:939–51.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Inacio P, Cavaco A, Airaksinen M. The value of patient reporting to the pharmacovigilance system: a systematic review. Br J Clin Pharmacol. 2017;83:227–46.PubMedCrossRefGoogle Scholar
  29. Jaquenoud Sirot E, van der Velden JW, Rentsch K, Eap CB, Baumann P. Therapeutic drug monitoring and pharmacogenetic tests as tools in pharmacovigilance. Drug Saf. 2006;29:735–68.PubMedCrossRefGoogle Scholar
  30. Lader M. Some adverse effects of antipsychotics: prevention and treatment. J Clin Psychiatry. 1999;60(Suppl 12):18–21.PubMedGoogle Scholar
  31. Lai EC, Pratt N, Hsieh CY, Lin SJ, Pottegard A, Roughead EE, Kao Yang YH, Hallas J. Sequence symmetry analysis in pharmacovigilance and pharmacoepidemiologic studies. Eur J Epidemiol. 2017;32:567–82.PubMedCrossRefGoogle Scholar
  32. Martin LG, Hanssens Y, Paudyal V. Overview of this issue: pharmacovigilance, what is new? Int J Clin Pharm. 2018;40:737–9.PubMedCrossRefGoogle Scholar
  33. Meyboom RH, Egberts AC, Gribnau FW, Hekster YA. Pharmacovigilance in perspective. Drug Saf. 1999;21:429–47.PubMedCrossRefGoogle Scholar
  34. Moore TJ, Cohen MR, Furberg CD. Serious adverse drug events reported to the food and drug administration, 1998-2005. Arch Intern Med. 2007;167:1752–9.PubMedCrossRefGoogle Scholar
  35. Olsson S, Pal SN, Dodoo A. Pharmacovigilance in resource-limited countries. Expert Rev Clin Pharmacol. 2015;8:449–60.PubMedCrossRefGoogle Scholar
  36. Osanlou O, Pirmohamed M, Daly AK. Pharmacogenetics of adverse drug reactions. Adv Pharmacol. 2018;83:155–90.PubMedCrossRefGoogle Scholar
  37. Perroud N. Suicidal ideation during antidepressant treatment: do genetic predictors exist? CNS Drugs. 2011;25:459–71.PubMedCrossRefGoogle Scholar
  38. Pitts PJ, Louet HL, Moride Y, Conti RM. 21st century pharmacovigilance: efforts, roles, and responsibilities. Lancet Oncol. 2016;17:e486–e92.PubMedCrossRefGoogle Scholar
  39. Potts J, Genov G, Segec A, Raine J, Straus S, Arlett P. Improving the safety of medicines in the EU: from signals to action. Clin Pharmacol Ther. 2019;107(3):521–9.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Rajkumar RP, Melvin G. Pharmacovigilance for psychiatrists: an introduction. Indian J Psychiatry. 2014;56:176–81.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Ralph EI. Causality assessment in pharmacovigilance: still a challenge. Drug Saf. 2017;40:365–72.CrossRefGoogle Scholar
  42. Schütze G, Schwarz MJ. Therapeutic drug monitoring for individualised risk reduction in psychopharmacotherapy. TrAC Trends Anal Chem. 2016;84:14–22.CrossRefGoogle Scholar
  43. Toledano R, Gil-Nagel A. Adverse effects of antiepileptic drugs. Semin Neurol. 2008;28:317–27.PubMedCrossRefGoogle Scholar
  44. Vargesson N. Thalidomide-induced teratogenesis: history and mechanisms. Birth Defects Res C Embryo Today. 2015;105:140–56.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Verheijen RB, Yu H, Schellens JHM, Beijnen JH, Steeghs N, Huitema ADR. Practical recommendations for therapeutic drug monitoring of kinase inhibitors in oncology. Clin Pharmacol Ther. 2017;102:765–76.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Villalba-Moreno AM, Alfaro-Lara ER, Perez-Guerrero MC, Nieto-Martin MD, Santos-Ramos B. Systematic review on the use of anticholinergic scales in poly pathological patients. Arch Gerontol Geriatr. 2016;62:1–8.PubMedCrossRefGoogle Scholar
  47. Westerdijk K, Desar IME, Steeghs N, van der Graaf WTA, van Erp NP. Imatinib, sunitinib and pazopanib: from flat-fixed dosing towards a pharmacokinetically guided personalized dose. Br J Clin Pharmacol. 2019;86(2):258–73.CrossRefGoogle Scholar
  48. WHO-UMC. The use of the WHO-UMC system for standardised case causality assessment. World Health Organisation – the Uppsala Monitoring Centre. Accessed 13 Dec 2019.
  49. WHO. Pharmacovigilance: ensuring the safe use of medicines. Geneva: World Health Organization; 2004. Accessed 22 Nov 2019Google Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Psychiatry, Psychosomatics and PsychotherapyUniversity Hospital of WürzburgWürzburgGermany

Section editors and affiliations

  • Peter Riederer
    • 1
  1. 1.Center of Mental HealthDepartment of Psychiatry, Psychosomatics and Psychotherapy, University Hospital WürzburgWürzburgGermany

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