Proton pump inhibitor deprescription: A rapid review

Imparato, Renata Rodriguez; Toma, Tereza Setsuko

doi:10.1590/s2175-97902022e19989

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Brazilian Journal of Pharmaceutical Sciences

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Article • Braz. J. Pharm. Sci. 58 • 2022 • https://doi.org/10.1590/s2175-97902022e19989 copy

Proton pump inhibitor deprescription: A rapid review

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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

BASE	DATE	STRATEGY	NUMBER OF ARTICLES
LILACS	07/07/2019	(Desprescrições OR Deprescriptions OR Deprescripciones OR Deprescrição OR Deprescrições OR Desprescrição) AND (“Inibidores da Bomba de Prótons” OR “Proton Pump Inhibitors” OR “Inhibidores de la Bomba de Protones”)	0
PUBMED	07/07/2019	((("Proton Pump Inhibitors"[Mesh] OR Inhibitors, Proton Pump)) OR ("Omeprazole"[Mesh] OR Prilosec OR Omeprazole Sodium OR Sodium, Omeprazole OR H 168-68 OR H 168 68 OR H 16868 OR Omeprazole Magnesium OR Magnesium, Omeprazole)) AND ("Deprescriptions"[Mesh] OR Deprescription OR Deprescribing)	43
EMBASE	07/07/2019	('proton pump inhibitor'/exp OR 'omeprazole'/exp) AND 'deprescription'/exp AND [embase]/lim	42
NICE evidence	07/07/2019	(deprescription OR deprescribing) AND ("proton pump inhibitors" OR omeprazole)	33
TOTAL			118

Systematic Review	Deprescribing versus continuation of chronic proton pump	Effectiveness of interventions to deprescribe inappropriate proton pump inhibitors in older adults	Patient barriers to and enablers of deprescribing: A systematic review	Deprescribing medications for chronic diseases management in primary care settings: A systematic review of randomized controlled trials
Study designs and quantity	Prospective open multicenter randomized trial (n = 4).	Randomized controlled trials (n = 6) (one specific for PPI), prospective uncontrolled cohort (n = 8), interrupted time series (n = 2), pre and post-intervention audits (n = 3), retrospective uncontrolled cohort (n = 1), multicenter prospective cohort without control (n = 1).	Qualitative: Semi-structured interview (n = 11). -Focus group (n = 2).	Randomized clinical trials (n = 58).
	Prospective randomized doubleblind multicenter trial (n = 2).		Qualitative (mixed): - Open answers (n = 1), semistructured interview (n = 5), open and closed answers (n = 1).
			Quantitative: - Research (n = 1).
Latest search date	November 2016	January 2017	August 2011	December 2016
AMSTAR 2	Methodological quality assessment: high	Methodological quality assessment: moderate	Methodological quality assessment: moderate	Methodological quality assessment: moderate
Intervention in detail Deprescription: - On demand regarding the continuous use of PPI in outpatients (average 48	Deprescription: - On demand regarding the continuous use of PPI in outpatients (average 48 to 57 years) with moderate GERD and mild esophagitis. Abrupt compared to continued use of PPI in outpatients (age> 18 years /average 73 years) with mild to moderate esophagitis	Discharge counseling (n = 1), outpatient clinics with focus on deprescription (n = 2), education for doctors and pharmacists (n = 5), academic detailing (n = 2), geriatrician management (n = 5) or revision of ME (n = 6).	Semi - structured interview, focus group, questionnaire survey.	To refine the amount of ME:
		-Deprescription of PPI:	Boath and Blenkinsopp (1997) n = 20 and Grime et al. (2001) n = 82: Qualitative research with semi - structured interviews in the United Kingdom report barriers and enablers for PPI deprescription.	Educational interventions: Training of health professionals
		a) Evidence-based educational material (leaflets) provided to physicians, pharmacists and patients.		-Specific interventions: Educative targeted at highrisk patients individually on the management of chronic diseases and the inappropriate use of ME in an inpatient, outpatient and long term care settings.
		b) Academic detailing: teaching sessions.		- Mixed intervention (prescriptive and patient specific).
		c) Deprescription by a geriatrician.		PPI deprescription: mixed educational interventions.
Participants	Participants (n = 1758) between 48 and 57 years old. One study (Pilotto 2003) included participants aged 65 old and older (average age 73 years old). All participants were outpatient and had non-erosive reflux disease or milder degrees of esophagitis (LA grade A or B).	Participants with a median age of 65 years old on inadequate PPI use.	Participants (n = 1310) in use or recently suspended use of ME.	Non-terminal adults 18 years old and older
Place	Morgan 2007: 23 canadian locations. Pilotto 2003: 16 italian centers. Van der Velden 2010: 23 general practices of the central and eastern Netherlands. Bour 2005: 41 french hospitals (exact undisclosed locations). Janssen 2005: 58 centers (29 in Germany, 12 in France, 11 in Switzerland and 6 in Hungary). Bayerdörffer 2016: 61 sites (Austria, France, Germany, South Africa and Spain).	Hospitals and community or elderly care facilities.	Not informed.	Ambulatory, assisted living environments and nursing home.
Countries	Canada, Italy, the Netherlands, France, Germany, Switzerland, Hungary, Austria, South Africa and Spain.	Australia, New Zealand, USA, England, Wales, Scotland, Ireland, France, Switzerland, Germany, Netherlands and Israel.	United States, United Kingdom, Australia, Israel, Netherlands, Sweden.	Finland, Spain, United States, New Zealand, Canada, Sweden, Belgium, Germany, Australia, Israel, United Kingdom, France, Ireland, Norway, Netherlands, Denmark, Brazil.
Outcomes and Results	Primary outcomes: lack of symptom control = return of symptoms or inadequate relief, use of ME (including PPI) and cost (no report). Secondary outcome: Positive result (no report), all negative results or adverse withdrawal event (exception: gastrointestinal symptoms) and participant satisfaction. The six studies measured the lack of symptom control and analyzed data separately for on demand deprescription and abrupt discontinuation.	Studies with effective interventions (n = 6). Inconclusive studies (n = 11), ineffective studies (n = 4). Effective interventions for PPI: Roughead et al. and Pratt et al.: PPI specific with educational material for physicians, pharmacists and patients: a) Increase of 0.6%/month in the low dose prescription rate and increase to 0.9% per month after 20 months (p = 0.007). b) Decrease of 8.47% in the prescription rate (95% CI -13.72 to -3.21%) compared to the rate without intervention. c) Increase of 1.57% in the rate of use of low dose PPI (95% CI 0.71-2.44%). - Clyne et al. 2015 and 2016 reported the intervention of “scholarly detailing “: Pharmacist visit to clinics to discuss potentially inappropriate prescriptions, ME review, and the algorithm. The adjusted OR of continuing to receive an inadequate PPI in the intervention group compared to the group increased from 0.3 at six months to 0.4 after one year of study.	Barriers reported by patients: Disagreement with deprescription, deprescription process, negative influencers, fear and others. Enablers: Agreement to discontinue the medication, deprescription process, positive influencers, antipathy to ME, others.	Primary outcome: Successful deprescription. Statistically significant reduction in ME burden between the intervention group (IG) and the control group (CG). More than 50% of patients tolerated drug deprescription compared with the control.
	1) On demand prescription vs. PPI continuous therapy: Bour 2005 and Janssen 2005 evaluated treatment failure. Bayerdörffer 2016; Morgan 2007; Van der Velden 2010 assessed inadequate symptom relief: 16.3% of participants in the on demand prescription group experienced lack of symptom control versus 9.2% in continuous treatment (RR 1.71, 95% CI 1.31 to 2.21). Bayerdörffer 2016; Bour 2005; Janssen 2005 evaluated the number of PPI tablets: Reduction of use of 3.79 PPI tablets/week (95% CI -4.73 to -2.84). Bayerdorffer 2016 assessed adverse withdrawal events: 15 participants (5%) developed esophagitis with on demand deprescription compared to none with continued use of PPI. Bayerdörffer 2016; Bour 2005; Janssen 2005; Morgan 2007; Morgan 2007; Van der Velden 2010) assessed participant satisfaction (unwillingness to continue and inadequate symptom relief). Participants using on demand PPI showed greater dissatisfaction compared to participants using continuous PPI (15.8% with demand versus 8.8% with continuous; RR 1.82, 95% CI 1.26 to 2.65).		Influence of the pharmacological class.	Secondary outcome: Adverse effects related to the drug or chronic condition.
	2) Abrupt desprescription vs. continuous PPI therapy: Pilotto 2003 assessed treatment failure: Abrupt deprescription has been associated with an increased risk of return of gastrointestinal symptoms. Pilotto 2003 evaluated adverse withdrawal events: 69.6% of participants with a history of esophagitis relapsed with abrupt discontinuation compared with 20.4% with continuous treatment (RR 3.41, 95% CI 1.91, 6.09).	Michalek et al. and Wehling et al. reported deprescription by geriatricians and use of FORTA to guide prescribing.	- Barriers to the deprescription of PPI: 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 bad experienc es with previous deprescriptions.
			- Enablers for the deprescription of PPI: Fear of adverse effects, possibility of restarting medication use, influence of primary care physician, and cost of medication.	- Deprescription of PPI:
				a) Zwisler et al. 2015 (n = 171), randomized, double-blind, placebo-controlled study: Highest deprescription rate was 27% of participants.
				b) Clyne et al. 2015: Successful deprescribing (dose reduction to maintenance level in 50% of patients) with patient-specific pharmacist-related educational intervention for prescribers, related to potentially inappropriate medication (PIM) 20% of cases: suspension of use.
				Indication of alternative therapy: 11% unchanged behaviour: 20%.
Implementation barriers	Abrupt deprescription was associated with an increased risk of symptom recurrence.	Deprescription processes without involvement between physician and patient.	Need for drug: - Belief in the benefit of ME for the clinical condition (PPI and others), hope for future benefits, psychological wellbeing, unwillingness to try alternatives (PPI and others), desire to increase the dose of the drug, skepticism in the suspension recommendation.	Adverse results, worsening clinical condition and exacerbation of chronic diseases. Interventions can be costly, intensive and ongoing.
			- Fear: Return of clinical condition, return of symptoms (PPI and others), withdrawal effects, non-specific fears (PPI and others).
			- In the process of deprescription: Lack of support, unknown or conflicting information, need for adequate time.
			- Influences: From primary care physician, relatives and friends, bad experiences with previous withdrawals (PPI and others).
			- Other: Pragmatism, resistance to change, habit, unwillingness.
Implementation enablers	Possible reduction in the number of tablets if on demand deprescription is tolerated.	Evidence-based educational interventions, “scholarly detailing” involving pharmacist visits and geriatricianled deprescriptions.	Need for medication: - Presence of adverse effects, fear of adverse effects (PPI and others), belief that medication is not necessary, finding of ineffectiveness, fear of dependence, acceptance of alternative treatment option, uncertainty about need of treatment continuity, insecurity about the doctor who started the treatment.	Pharmacist’s intervention in the educative actions with the doctor and the patient, and in the specific recommendations in patient’s treatment.
			- Deprescription process: Possibility of restarting the use of medication (PPI and others), monitoring of primary care physician and other services, family support, factors related to cessation of stress.
			- Influences: Primary care physician (PPI and others), other influences.
			- Dislike: Psychological benefits, aversion to drug use, inconvenience, including cost (PPI and others), ME are unnatural, stigma.
			- Other: Absence of fear.
Knowledge Gaps	Best strategy for deprescription: Inconclusive.	Overcome knowledge barriers regarding inadequate PPI prescribing.	Proposal of deprescription for specific age groups, studies of deprescription with other classes of ME, evaluation of results regarding patientcentered deprescription.	Not informed
	Comparison of continuous therapy deprescription methods in populations with other gastrointestinal disorders (results limited to people with gastroesophageal reflux disease (GERD) presenting with NERD or mild esophagitis), broadening of population characteristics and extension of the mean followup after one year, cost-benefit analysis of adverse events of ME withdrawal and positive events of ME withdrawal and comparison of deprescribing outcomes in people with high-grade EE (erosive esophagitis).	Uncertainty whether PPI deprescription translates into better clinical outcomes. Discussion of strategies for deprescription (abrupt discontinuation, dose reduction, gradual reduction or use on demand).

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

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[1] *Correspondence: Renata Rodriguez Imparato. Instituto de Saúde. Rua Santo Antônio, 590. CEP: 01314-000, São Paulo, Brasil. Phone: 55 11 98297-1238. E-mail: reimparato@hotmail.com. ORCID: 0000-0001-6820-02936.