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Proton pump inhibitor deprescription: A rapid review

Abstract

Proton pump inhibitors (PPI) are drugs that suppress gastric acid secretion. Its use, without support from scientific evidence, can contribute to polypharmacy, lead to drug interactions and, in the long term, cause serious adverse reactions. Studies advise physicians to deprescribe PPI. A quick review of scientific evidence, also called a rapid systematic review, on the deprescribing of PPI was performed. Evidence searches were performed in the LILACS, Embase, PubMed and NICE evidence databases with the terms “omeprazole”, “proton pump inhibitors”, “deprescription”, “deprescribing”. At LILACS these descriptors were also used in Portuguese and Spanish. Of 118 studies identified, four systematic reviews were selected for analysis. Abrupt deprescribing was associated with an increased risk of symptom recurrence. Fear of symptom recurrence is one of the major barriers to patient-related deprescribing. Educational interventions directed at prescribers, pharmacists, and patients are effective strategies in the deprescribing of PPI. Deprescribing process showed to be feasible in different contexts, with different strategies. The process is most effective through actions with educational and guidance materials directed to health professionals and patients, and with the involvement or leadership of the pharmacist.

Keywords:
Proton pump inhibitors; Deprescription; Polypharmacy; Drug-related side effects and adverse reactions; Drug interactions

INTRODUCTION

Proton pump inhibitors (PPI) are drugs that suppress gastric acid secretion by inhibiting the enzyme H+/K+-ATPase, indicated for the treatment of gastric and duodenal ulcers, erosive esophagitis, eradication of H. pylori in combination with antibiotics, prophylaxis of ulcers associated with non-steroidal anti-inflammatory drugs and hypersecretory conditions such as Zollinger-Ellison syndrome. There is no evidence as to the benefit of using PPI for non-ulcer dyspepsia (Wallace, Sharkey, 2012Wallace JL, Sharkey KA. Farmacoterapia da acidez gástrica, úlceras pépticas e doença do refluxo gastroesofágico. In: Brunton LL, Chabiner BA, Knollmann BC, organizadores. As Bases Farmacológicas da Terapêutica de Goodman & Gilman - 12a edição. Porto Alegre. AMGH Editora LTDA. 2012. p. 1309-22. ).

For most acid secretion-related illnesses, the duration of PPI treatment varies from two to twelve weeks, but the efficacy, safety profile and tolerability of the drug stimulate long-term use without timely re-evaluation to determine the need for the drug maintenance (Boghossian et al., 2017Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas-Fernandez C, et al. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev. 2017;3:CD011969.).

Prolonged use is justified only in the treatment of complications of gastroesophageal reflux disease such as Barrett's esophagus, under hypersecretory conditions such as Zollinger-Ellison syndrome and in patients with erosive esophagitis (Wilsdon et al., 2017Wilsdon TD, Hendrix I, Thynne TR, Mangoni AA. Effectiveness of Interventions to Deprescribe Inappropriate Proton Pump Inhibitors in Older Adults. Drugs Aging. 2017;34(4):265-287.). However, according to Reimer et al. (2009Reimer C, Søndergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009;137(1):80-7.) the prevalence of long-term treatment is increasing and up to 70% of patients with chronic acid suppression do not have an indication for PPI treatment. The use of PPI has increased over the past decade, with no new indications being added to their use (Haastrup et al., 2014Haastrup P, Paulsen MS, Zwisler JE, Begtrup LM, Hansen JM, Rasmussen S, et al. Rapidly increasing prescribing of proton pump inhibitors in primary care despite interventions: a nationwide observational study. Eur J Gen Pract. 2014;20(4):290-3.), according to studies conducted in Denmark and the United Kingdom that reveal this increase after 1990 (Pottegård et al., 2016Pottegård A, Broe A, Hallas J, Muckadell OBS, Lassen AT, Lødrup AB. Use of proton-pump inhibitors among adults: a Danish nationwide drug utilization study. Therap Adv Gastroenterol. 2016;9(5):671-678.; Othman, Card, Crooks, 2016Othman F, Card TR, Crooks CJ. Proton pump inhibitor prescribing patterns in the UK: a primary care database study. Pharmacoepidemiol Drug Saf. 2016;25(9):1079-87.).

Patient safety is a relevant topic in the health policy agenda, and it is mandatory to consider it even before the effectiveness of medicines. Primary adverse effects associated with short-term use of PPI include headache, diarrhea, constipation, rash and nausea. Prolonged use may trigger drug interactions, such as reducing the antiplatelet effect of clopidogrel, as well as serious adverse effects such as pneumonia, hypomagnesemia, vitamin B12 deficiency, C. difficile infection, bone fractures, polyp formation (Fohl, Regal, 2011Fohl AL, Regal RE. Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all? World J Gastrointest Pharmacol Ther. 2011;2(3):17-26.; Ament, Dicola, James, 2012Ament PW, Dicola DB, James ME. Reducing adverse effects of proton pump inhibitors. Am Fam Physician. 2012;86(1):66-70.; Chubineh, Birk, 2012Chubineh S, Birk J. Proton Pump Inhibitors: The Good, the Bad and the Unwanted. South Med J. 2012;105(11):613-18. ), chronic and acute kidney disease, iron deficiency anemia, dementia (Gomm et al., 2010Gomm W, von Holt K, Thomé F, Broich K, Maier W, Fink A, et al. Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis. JAMA Neurol. 2016;73(4):410-6. ; Schoenfeld, Grady, 2016Schoenfeld AJ, Grady D. Adverse Effects Associated With Proton Pump Inhibitors. JAMA Intern Med. 2016;176(2):172-4.; Wilsdon et al., 2017Wilsdon TD, Hendrix I, Thynne TR, Mangoni AA. Effectiveness of Interventions to Deprescribe Inappropriate Proton Pump Inhibitors in Older Adults. Drugs Aging. 2017;34(4):265-287.; Guedes et al., 2020Guedes JVM, Aquino JA, Castro TLB, Morais FA, Baldoni AO, Belo VS, et al. Omeprazole use and risk of chronic kidney disease evolution. PLoS One. 2020;15(3):e0229344. Published 2020 Mar 4.).

Adverse effects may be confused with new diseases, leading to the prescription of other medications (Anthierens et al., 2010Anthierens S, Tansens A, Petrovic M, Christiaens T. Qualitative insights into general practitioners views on polypharmacy. BMC Fam Pract. 2010;11:65.). The chronic use of PPI, as a consequence, contributes to the increase in unnecessary costs for health systems and polypharmacy (Hasstrup et al., 2014; Boghossian et al., 2017Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas-Fernandez C, et al. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev. 2017;3:CD011969.). The increase in prevalence of chronic diseases, multidisciplinary prescriptions and pharmacological choices for health intervention contribute to polypharmacy and expose the elderly population to prescription of potentially inappropriate drugs, with the risk of adverse reactions outweighing the clinical benefits (Gomes et al. , 2019Gomes MS, Amorim WW, Morais RS, Gama RS, Graia LT, Queiroga HM, et al. Polypharmacy in older patients at primary care units in Brazil. Int J Clin Pharm. 2019;41(2):516-524., Oliveira et al., 2012Oliveira MG, Amorim WW, de Jesus SR, Rodrigues VA, Passos LC. Factors associated with potentially inappropriate medication use by the elderly in the Brazilian primary care setting. Int J Clin Pharm . 2012;34(4):626-632.).

This practice is common in the elderly and may be beneficial for treating various diseases, but is associated with increased risks of drug interactions, adverse reactions, falls, iatrogenesis, hospitalizations and mortality (Hilmer, Gnjidic, 2009Hilmer SN, Gnjidic D. The effects of polypharmacy in older adults. Clin Pharmacol Ther. 2009;85(1):86-8.; Gnjidic et al., 2012Gnjidic D, Le Couteur DG, Kouladjian L, Hilmer SN. Deprescribing trials: methods to reduce polypharmacy and the impact on prescribing and clinical outcomes. Clin Geriatr Med. 2012;28(2):237-53. ; Dills et al., 2018Dills H, Shah K, Messinger-Rapport B, Bradford K, Syed Q. Deprescribing Medications for Chronic Diseases Management in Primary Care Settings: A Systematic Review of Randomized Controlled Trials. J Am Med Dir Assoc. 2018;19(11):923-935.; Machado et al., 2017Machado-Alba JE, Gaviria-Mendoza A, Machado-Duque ME, Chica L. Deprescribing: a new goal focused on the patient. Expert Opin Drug Saf. 2017;16(2):111-112.; Motter et al., 2018Motter FR, Fritzen JS, Hilmer SN, Paniz ÉV, Paniz VMV. Potentially inappropriate medication in the elderly: a systematic review of validated explicit criteria. Eur J Clin Pharm. 2018;74(6):679-700. e Santos et al., 2019Santos NS, Marengo LL, Moraes FS, Barberato-Filho S. Interventions to reduce the prescription of inappropriate medicines in older patients. Rev Saude Publica. 2019;53:7.).

A population-based study, conducted in primary care in Brazil, observed a 47.4% prevalence of clinically important drug interactions in elderly patients (Obreli et al., 2012Obreli Neto PR, Nobili A, Marusic S, Pilger D, Guidoni CM, Baldoni AO, et al. Prevalence and predictors of potential drug-drug interactions in the elderly: a cross-sectional study in the brazilian primary public health system. J Pharm Pharm Sci. 2012;15(2):344-354.).

In recent years, the need to reduce over prescription of drugs through an approach called deprescription has been discussed. The term "deprescription" was first mentioned in 2003 in the article“Deprescribing: Achieving Better Health Outcomes for Older People Through Reducing Medications”. It is a process planned and supervised by a healthcare professional to reduce, replace or discontinue inappropriate medications to control polypharmacy (Woodward, 2003Woodward MC. Deprescribing: Achieving Better Health Outcomes for Older People Through Reducing Medications. J Pharm Pract Res. 2003;33(4):323-28.; Reeve et al., 2015Reeve E, Gnjidic D, Long J, Hilmer S. A systematic review of the emerging definition of 'deprescribing' with network analysis: implications for future research and clinical practice. Br J Clin Pharmacol . 2015;80(6):1254-68.). Scott et al. (2015Scott IA, Hilmer SN, Reeve E, Potter K, Le Couteur D, Rigby D, et al. Reducing inappropriate polypharmacy: the process of deprescribing. JAMA Intern Med . 2015;175(5):827-34., p. 827) define deprescription as “the systematic process of identifying and discontinuing drugs in cases where existing or potential harm outweighs existing or potential benefits (...)”. Considers the same principles as starting a prescribed therapy, ie, it is a patient-centered process with shared decision making and monitoring of effects.

Planning this process involves recognizing polypharmacy and knowing the list of drugs used by the patient and their indications, identifying inappropriate drugs, evaluating each one and setting priorities for deprescribing, implementing the strategy, and monitoring withdrawal syndrome, rebound effect, recurrence of the disease and patient´s quality of life (Couteur et al., 2011Couteur DL, Banks E, Gnjidic D, McLachlan A. Deprescribing. Australian Prescriber. 2011;34(6):182-85. ; Reeve et al., 2013Reeve E, To J, Hendrix I, Shakib S, Roberts MS, Wiese MD. Patient barriers to and enablers of deprescribing: a systematic review. Drugs Aging. 2013;30(10):793-807.; Machado et al., 2017Machado-Alba JE, Gaviria-Mendoza A, Machado-Duque ME, Chica L. Deprescribing: a new goal focused on the patient. Expert Opin Drug Saf. 2017;16(2):111-112.; Santos et al., 2019Santos NS, Marengo LL, Moraes FS, Barberato-Filho S. Interventions to reduce the prescription of inappropriate medicines in older patients. Rev Saude Publica. 2019;53:7.).

The beneficial consequences of deprescription include the cessation of adverse reactions and drug interactions. It includes also the minimization of future risks, reduced patient and health care costs, improved treatment adherence and patient´s quality of life, and a decreased medication associated errors (Couteur et al., 2011Couteur DL, Banks E, Gnjidic D, McLachlan A. Deprescribing. Australian Prescriber. 2011;34(6):182-85. ).

MATERIAL AND METHODS

A quick review of the scientific literature on PPI was conducted, with emphasis on deprescription. The quick review, also called the systematic rapid review, is a secondary study design that has been increasingly used to inform health policies, especially useful for managers and decision makers (Bortoli et al., 2017Bortoli MC, Setti C, Lima FJS, Dalenogare GV. Mecanismos e programas de revisão rápida. In: Toma TS, Pereira TV, Vanni T, Barreto JOM, organizadores. Avaliação de Tecnologias de Saúde & Políticas Informadas por Evidências. São Paulo, Imprensa Oficial do Estado S/A - IMESP. 2017;105-108).

The search for scientific evidence was performed in the LILACS, Embase, PubMed and NICE evidence databases on July 7, 2019, without the use of filters. The terms extracted from the Descriptors in Health Sciences - DeHS and the Medical Subject Headings (MeSH) were used. In Embase, PubMed and Nice Evidence, the terms “omeprazole”, “proton pump inhibitors”, “deprescription” and “deprescribing” were used. The same search strategy was employed in LILACS, however, including also the descriptors in Portuguese and Spanish. The details of the search strategy are in Table I.

TABLE I
Search strategies in scientific literature databases

The article selection process was performed by the author and discussed with the co-author, starting with reading the titles, followed by reading the abstracts and later the full articles. Inclusion criteria were: Systematic reviews, published in English, Spanish and Portuguese. The selected systematic reviews were evaluated for methodological quality through the Assessment of Multiple Systematic Reviews - AMSTAR 2 instrument (Shea et al., 2017Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008.), being applied by the author, followed by discussion with the co-author. The SR were classified as high (13-16/16), moderate (9-12/16), low (5-8/16) and critically low (0-4/16) methodological quality. The data were extracted from the SR by the author in an Excel spreadsheet, containing the following information: author/year, objective, quantity and study designs included, most recent search date, AMSTAR 2 score, intervention studied, participant characteristics, location and countries of achievement, outcomes, barriers to implementation, facilitators of implementation and knowledge gaps (Table II).

TABLE II
Characteristics of the included studies

RESULTS

The searches allowed to identify 118 studies, of which six SR were considered eligible and four were selected, according to the selection process presented in Figure 1.

FIGURE 1
Study selection flow chart

The systematic reviews of Page et al., 2016Page AT, Clifford RM, Potter K, Schwartz D, Etherton-Beer CD. The feasibility and effect of deprescribing in older adults on mortality and health: a systematic review and meta-analysis. Br J Clin Pharmacol. 2016;82(3):583-623. and Malhotra et al., 2018Malhotra K, Katsanos AH, Bilal M, Ishfaq MF, Goyal N, Tsivgoulis G. Cerebrovascular outcomes with proton pump inhibitors and thienopyridines: A systematic review and meta-analysis. Stroke. 2018;49(2):312-318. were excluded because they did not contemplate the objectives of this study. Of the four SR included, one is of high methodological quality and the others of moderate quality.

Two of the included systematic reviews specifically address PPI (Boghossian et al., 2017Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas-Fernandez C, et al. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev. 2017;3:CD011969.; Wilsdon et al., 2017Wilsdon TD, Hendrix I, Thynne TR, Mangoni AA. Effectiveness of Interventions to Deprescribe Inappropriate Proton Pump Inhibitors in Older Adults. Drugs Aging. 2017;34(4):265-287.) to determine the effects (Boghossian et al., 2017Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas-Fernandez C, et al. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev. 2017;3:CD011969.) and effectiveness of interventions (Wilsdon et al., 2017Wilsdon TD, Hendrix I, Thynne TR, Mangoni AA. Effectiveness of Interventions to Deprescribe Inappropriate Proton Pump Inhibitors in Older Adults. Drugs Aging. 2017;34(4):265-287.) associated with deprescribing. The third analyzed barriers and facilitators that influence the patient in the decision to deprescribe (Reeve et al., 2013Reeve E, To J, Hendrix I, Shakib S, Roberts MS, Wiese MD. Patient barriers to and enablers of deprescribing: a systematic review. Drugs Aging. 2013;30(10):793-807.) and the fourth evaluated the result of deprescription in reducing the amount of medication and controlling medical conditions (Dills et al., 2018Dills H, Shah K, Messinger-Rapport B, Bradford K, Syed Q. Deprescribing Medications for Chronic Diseases Management in Primary Care Settings: A Systematic Review of Randomized Controlled Trials. J Am Med Dir Assoc. 2018;19(11):923-935.).

Boghossian et al. (2017Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas-Fernandez C, et al. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev. 2017;3:CD011969.) analyzed the effects of two strategies (n=1758): on demand PPI deprescription in patients aged 48 to 57 years old with moderate gastroesophageal reflux disease and mild esophagitis, and abrupt deprescription in patients ≥ 65 years old with mild to moderate esophagitis compared to continuous use (28 days or more). In the on-demand deprescription, 16.3% of participants had return of gastrointestinal symptoms or inadequate relief versus 9.2% in continuous use (RR 1.71; 95% CI 1.31 to 2.21). Fifteen participants in the intervention group developed esophagitis compared to none in the control group. There was a reduction in use on average, of 3.79 tablets of PPI/week (95% CI -4.73 to -2.84). The use of PPI on demand caused greater dissatisfaction among participants compared to the control group, respectively 15.8% and 8.8% (RR 1.82; 95% CI 1.26 to 2.65). Abrupt deprescription was associated with an increased risk of symptom recurrence, with relapse in 69.6% of participants with a history of esophagitis compared with 20.4% of those with continuous PPI use (RR 3.41; 95% CI 1.91 to 6.09).

Wilsdon et al. (2017Wilsdon TD, Hendrix I, Thynne TR, Mangoni AA. Effectiveness of Interventions to Deprescribe Inappropriate Proton Pump Inhibitors in Older Adults. Drugs Aging. 2017;34(4):265-287.) reported effective and targeted interventions to promote high-dose-reduced PPI deprescription through educational material (leaflets) prepared on the basis of scientific evidence directed to physicians, pharmacists and patients who were in different programs and periods in Australia. The number of low-dose prescriptions increased by 0.6% per month and after 20 months increased to 0.9% per month (p = 0.007). In one of the studies reviewed, these interventions were rated as useful or very useful by 81% of physicians, 95% of pharmacists and 72% of patients.

Reeve et al. (2013Reeve E, To J, Hendrix I, Shakib S, Roberts MS, Wiese MD. Patient barriers to and enablers of deprescribing: a systematic review. Drugs Aging. 2013;30(10):793-807.) studied 1310 participants who were taking or recently discontinuing use of drugs, in order to identify barriers and facilitators that may influence the patient's decision to deprescribe. Two qualitative studies analyzed were conducted in the United Kingdom and cite as barriers to PPI deprescription: Belief in the benefit of the drug for the clinical condition, unwillingness to try alternatives, fear of the return of the clinical condition or the return of symptoms and poor experiences with previous deprescription. On the other hand, the fear of adverse effects, the possibility of restarting the use of the medication, the influence of the primary care physician and the cost of the medication were cited as facilitators of the PPI deprescription.

Dills et al. (2018Dills H, Shah K, Messinger-Rapport B, Bradford K, Syed Q. Deprescribing Medications for Chronic Diseases Management in Primary Care Settings: A Systematic Review of Randomized Controlled Trials. J Am Med Dir Assoc. 2018;19(11):923-935.) included adult participants over 18 years old to evaluate the outcome of deprescribing in reducing the amount of medication and in controlling medical conditions. Pharmacist-led educational interventions on symptom management and prescription, directed at prescribers and patient-directed educational interventions on inappropriate drug use resulted in a reduction in PPI dose to maintenance dose in 50% of patients.

DISCUSSION

This review has limitations inherent in the design of a quick review, such as fewer databases searched, selection processes and data extraction not performed independently, focusing on systematic reviews. On the other hand, this type of review has the advantage of providing timely answers to the demands of managers in the daily routine of health services.

Deprescription is a process that begins prior to the formal act of prescribing a change in conduct. For the deprescription process to be developed effectively and safely, barriers must be considered by both doctors and patients. Confidence in drug therapy for cure or remission of symptoms, limited time for consultation with the healthcare professional, fear of discontinuation of therapy initiated by another prescriber, market influences, lack of communication between prescribers, disagreement between professionals and patients regarding the strategy for deprescription, lack of knowledge in the management of deprescription are barriers experienced by prescribers. In addition, patient resistance to discontinuation or replacement of therapy for fear of symptom recurrence, reporting of unsuccessful experiences of others and pressure from family and community to continue drug use should be considered (Reeve et al., 2013Reeve E, To J, Hendrix I, Shakib S, Roberts MS, Wiese MD. Patient barriers to and enablers of deprescribing: a systematic review. Drugs Aging. 2013;30(10):793-807.; Boghossian et al., 2017Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas-Fernandez C, et al. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev. 2017;3:CD011969.; Wilsdon et al., 2017Wilsdon TD, Hendrix I, Thynne TR, Mangoni AA. Effectiveness of Interventions to Deprescribe Inappropriate Proton Pump Inhibitors in Older Adults. Drugs Aging. 2017;34(4):265-287.; Dills et al., 2018Dills H, Shah K, Messinger-Rapport B, Bradford K, Syed Q. Deprescribing Medications for Chronic Diseases Management in Primary Care Settings: A Systematic Review of Randomized Controlled Trials. J Am Med Dir Assoc. 2018;19(11):923-935.). Patient education about the risks and benefits of drug therapy, a structured process of drug withdrawal, monitoring and support facilitate deprescription (Dills et al., 2018Dills H, Shah K, Messinger-Rapport B, Bradford K, Syed Q. Deprescribing Medications for Chronic Diseases Management in Primary Care Settings: A Systematic Review of Randomized Controlled Trials. J Am Med Dir Assoc. 2018;19(11):923-935.).

Boghossian et al. (2017Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas-Fernandez C, et al. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev. 2017;3:CD011969.) demonstrated that abrupt deprescription was associated with an increased risk of recurrence of gastric symptoms. In the case of PPI, deprescription may be performed with abrupt discontinuation, use on demand until relief of gastric symptoms, use of a lower dose or alternative therapy such as histamine-2 receptor antagonists (Thompson et al., 2018Thompson W, Black C, Welch V, Farrell B, Bjerre LM, Tugwell P. Patient Values and Preferences Surrounding Proton Pump Inhibitor Use: A Scoping Review. Patient. 2018;11(1):17-28.). Despite gaps in the scientific literature regarding agreement on the best strategy for deprescription, considering the clinical effects, the gradual on demand or dose-reduction process of PPI is more effective in controlling the recurrence of gastric symptoms compared to an abruptly withdrawal. (Katz, Gerson, Vela, 2013Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308-28.; Haastrup et al., 2014Haastrup P, Paulsen MS, Zwisler JE, Begtrup LM, Hansen JM, Rasmussen S, et al. Rapidly increasing prescribing of proton pump inhibitors in primary care despite interventions: a nationwide observational study. Eur J Gen Pract. 2014;20(4):290-3.; Farrell et al., 2017Farrell B, Pottie K, Thompson W, Boghossian T, Pizzola L, Rashid FJ, et al. Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline. Can Fam Physician. 2017;63(5):354-364.). According to Reimer et al. (2009Reimer C, Søndergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009;137(1):80-7.) abrupt withdrawal of PPI after 8 weeks of treatment may cause rebound acid hypersecretion in healthy adults. In a qualitative study, patients reported that they would use PPI at low or on demand doses (Grime, Pollock, 2002Grime JC, Pollock K. How do younger patients view long-term treatment with proton pump inhibitors? J R Soc Promot Health. 2002;122(1):43-9.).

It is very important to take these findings into account, as the fear of recurrence of gastric symptoms, associated with an increased risk of abrupt withdrawal, is one of the main barriers to deprescription, in addition to the belief in the benefit of the drug, unwillingness to try alternatives, bad experiences with previous deprescriptions processes and costs. Patients consider the use of PPI for clinical treatment necessary, value the control of gastric symptoms and the quality of life provided by their use and point this class of drugs as the most effective for this purpose (Spijker-Huiges, Winters, Meyboom-De Jong, 2006Spijker-Huiges A, Winters JC, Meyboom-De Jong B. Patients' views on dyspepsia and acid suppressant drug therapy in general practice. Eur J Gen Pract . 2006;12(1):10-4. ; Farrell et al., 2017Farrell B, Pottie K, Thompson W, Boghossian T, Pizzola L, Rashid FJ, et al. Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline. Can Fam Physician. 2017;63(5):354-364.; Thompson et al., 2018Thompson W, Black C, Welch V, Farrell B, Bjerre LM, Tugwell P. Patient Values and Preferences Surrounding Proton Pump Inhibitor Use: A Scoping Review. Patient. 2018;11(1):17-28.). In the study by Spijker-Huiges, Winters, Meyboom-De Jong (2006Spijker-Huiges A, Winters JC, Meyboom-De Jong B. Patients' views on dyspepsia and acid suppressant drug therapy in general practice. Eur J Gen Pract . 2006;12(1):10-4. ) 68% of patients reported that they would not accept the return of any symptoms after deprescription.

Systematic reviews by Wilsdon et al. (2017Wilsdon TD, Hendrix I, Thynne TR, Mangoni AA. Effectiveness of Interventions to Deprescribe Inappropriate Proton Pump Inhibitors in Older Adults. Drugs Aging. 2017;34(4):265-287.) and Dills et al. (2018Dills H, Shah K, Messinger-Rapport B, Bradford K, Syed Q. Deprescribing Medications for Chronic Diseases Management in Primary Care Settings: A Systematic Review of Randomized Controlled Trials. J Am Med Dir Assoc. 2018;19(11):923-935.) showed that information directed to physicians, pharmacists and patients through educational actions involving teaching materials and explanatory content on the promotion of rational use of medicines, as well as guides and algorithms, guide the conduct in the deprescription process. Based on the awareness of health professionals about prescribing and symptom management, the deprescription process can be relied on through the use of tools for guidance (Walsh et al., 2016Walsh K, Kwan D, Marr P, Papoushek C, Lyon WK. Deprescribing in a family health team: a study of chronic proton pump inhibitor use. J Prim Health Care. 2016;8(2):164-71.; Farrell et al., 2017Farrell B, Pottie K, Thompson W, Boghossian T, Pizzola L, Rashid FJ, et al. Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline. Can Fam Physician. 2017;63(5):354-364.).

In partnership with groups from other countries, Brazilian investigators performed the translation and cultural adaptation of deprescribing algorithms developed by the Canadian Deprescribing Network (Caden) for various drugs, including PPI (Sbrafh, 2020Sbrafh - Sociedade Brasileira de Farmácia Hospitalar e Serviços de Saúde [citad 2020 jul 1]. Disponível em: Disponível em: http://www.sbrafh.org.br/inicial/desprescricao/
http://www.sbrafh.org.br/inicial/despres...
).

According to Thompson et al. (2018Thompson W, Black C, Welch V, Farrell B, Bjerre LM, Tugwell P. Patient Values and Preferences Surrounding Proton Pump Inhibitor Use: A Scoping Review. Patient. 2018;11(1):17-28.) physicians are also afraid of the return of adverse effects in the face of deprescribing, so a strategy to guide deprescribing should include the identification, evaluation and prioritization of drugs in relation to the potential for risk, in a shared way between doctors and pharmacists. The time limitation on primary care physicians imposed by the routine of the service, however, implies the lack of reevaluation of continuous use medications (Thompson et al., 2018Thompson W, Black C, Welch V, Farrell B, Bjerre LM, Tugwell P. Patient Values and Preferences Surrounding Proton Pump Inhibitor Use: A Scoping Review. Patient. 2018;11(1):17-28.).

In the midst of a process that involves technical knowledge, established care routines and patients' anxieties, the experiences and expectations should be considered and discussed as a component for the shared development of the best strategy for deprescribing. The adverse effects of long-term PPI use worry patients in inverse proportion to the degree of satisfaction with symptom control and the costs incurred to maintain treatment (Chey, Mody, Izat, 2010Chey WD, Mody RR, Izat E. Patient and Physician Satisfaction with Proton Pump Inhibitors (PPIs): Are There Opportunities for Improvement? Dig Dis Sci. 2010;55(12):3415-22. ). According to studies (Farrell et al., 2017Farrell B, Pottie K, Thompson W, Boghossian T, Pizzola L, Rashid FJ, et al. Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline. Can Fam Physician. 2017;63(5):354-364.; Thompson et al., 2018Thompson W, Black C, Welch V, Farrell B, Bjerre LM, Tugwell P. Patient Values and Preferences Surrounding Proton Pump Inhibitor Use: A Scoping Review. Patient. 2018;11(1):17-28.), patients agree to discuss over prescription, are willing to decrease PPI use, and information exchange is important in this process. The patient is interested in understanding what is, how effective is, what actions and options are considered in view of the different outcomes, especially the occurrence of symptom recurrence and the possibility of resumption of PPI treatment. In the study by Smeets et al. (2009Smeets HM, De Wit NJ, Delnoij DM, Hoes AW. Patient attitudes towards and experiences with an intervention programme to reduce chronic acid-suppressing drug intake in primary care. Eur J Gen Pract . 2009;15(4):219-25.), patients considered the clarification of their involvement, the reasons for the deprescription, and the possibility of symptom recurrence to be of greater importance in the deprescription process.

In this sense, the inclusion of the pharmacist in health teams and their involvement in actions related to the promotion of rational use of medicines, educational actions to provide patient education and review of the list of medicines used, becomes increasingly relevant. This includes also monitoring symptoms in a shared and complementary manner to the physician (Farrell et al., 2017Farrell B, Pottie K, Thompson W, Boghossian T, Pizzola L, Rashid FJ, et al. Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline. Can Fam Physician. 2017;63(5):354-364.); and reducing indiscriminate drug use and health system costs (Bundeff, Zaiken, 2013Bundeff AW, Zaiken K. Impact of clinical pharmacists' recommendations on a proton pump inhibitor taper protocol in an ambulatory care practice. J Manag Care Pharm. 2013;19(4):325-33).

The studies included in this review were conducted in Europe, the United States and the Middle East and show that deprescription is feasible in different contexts with different strategies. The findings of the systematic reviews indicate that the process is most effective through actions with educational and guiding materials directed to health professionals and patients, with the involvement or leadership of the pharmacist. There were no studies conducted in Brazil on PPI deprescription, however, at the care level, the factors implicated in greater effectiveness and the actors involved are generally common to health systems, yet adaptations may be necessary to adapt to the local reality.

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Publication Dates

  • Publication in this collection
    18 July 2022
  • Date of issue
    2022

History

  • Received
    26 Nov 2019
  • Accepted
    16 Aug 2020
Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br