Strategies for discontinuation of proton pump inhibitors (PPIs) in patients with long-term PPI administration: a randomized controlled trial

Background Proton pump inhibitors (PPIs), including potassium ion-competitive acid blocker, are widely used worldwide and are often used for long periods of time. However, in recent years, potential side effects associated with long-term PPI use have been reported. Many patients take PPI for a long period of time, even though it is unnecessary, and it is necessary to discontinue PPI administration in such patients. However, sudden discontinuation may cause symptoms to recur and discontinuation may be unsuccessful. A strategy for safe and secure PPI discontinuation has not yet been established. The purpose of this study is to determine whether PPI can be safely discontinued by tapering the PPI dose or by abrupt discontinuation of PPI, and to establish a strategy for safe and secure PPI discontinuation. Methods The evaluation will be conducted as a multicenter, randomized, parallel-group clinical trial with five assessment points at the start of the study and 2 weeks, 4 weeks, 6 months, and 12 months after the start of the study. One intervention group is the group in which PPI administration is abruptly discontinued (Group A), and the second group is the group in which the PPI dose is gradually tapered and then PPI administration is discontinued (Group B). The primary outcome and secondary outcome are the proportion of patients who successfully discontinued the PPI at 6 months and at 12 months after the start of the study in groups A and B, respectively. Discussion We predict that the proportion of patients who successfully discontinue PPI will be higher in the group in which PPI administration was gradually tapered than in the group in which PPI administration was abruptly discontinued. On the other hand, we expect that many participants will succeed in discontinuing PPI regardless of the discontinuation strategy due to the explanation that discontinuation is necessary. Trial registration Japan Registry of Clinical Trials, jRCT1031180383. Registered 20 March 2019, https://jrct.niph.go.jp/latest-detail/jRCT1031180383.

Domperidone Withdrawal in a Nursing Female with Pre-existing Psychiatric Illness: Case Report

Background: In this report, we describe a case of domperidone withdrawal in a woman with a history of major depressive disorder and obsessive-compulsive disorder (OCD) who experienced a recurrence of these disorders after stopping domperidone. Case presentation: The symptoms improved after the restarting of domperidone and disappeared gradually as the drug was tapered and discontinued. Clinicians should consider domperidone withdrawal a differential diagnosis in women with a history of depression or anxiety who present with an acute onset of these symptoms following the abrupt discontinuation of domperidone. Conclusion: A gradual taper off of the drug may be effective in minimizing withdrawal symptoms and obviate the need for psychotropic drug use.

Philadelphia-Negative Chronic Myeloproliferative Neoplasms during the COVID-19 Pandemic: Challenges and Future Scenarios

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) started in December 2019 in China and then become pandemic in February 2020. Several publications investigated the possible increased rate of COVID-19 infection in hematological malignancies. Based on the published data, strategies for the management of chronic Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are provided. The risk of severe COVID-19 seems high in MPN, particularly in patients with essential thrombocythemia, but not negligible in myelofibrosis. MPN patients are at high risk of both thrombotic and hemorrhagic complications and this must be accounted in the case of COVID-19 deciding on a case-by-case basis. There are currently no data to suggest that hydroxyurea or interferon may influence the risk or severity of COVID-19 infection. Conversely, while the immunosuppressive activity of ruxolitinib might pose increased risk of infection, its abrupt discontinuation during COVID-19 syndrome is associated with worse outcome. All MPN patients should receive vaccine against COVID-19; reassuring data are available on efficacy of mRNA vaccines in MPNs.

348 Absence of Withdrawal Symptoms and Rebound Insomnia Upon Discontinuation of Daridorexant in Patients with Insomnia

Introduction Abrupt discontinuation of sleep medications in patients with insomnia often causes withdrawal symptoms and rebound insomnia. In a Phase 3 program evaluating efficacy and safety of daridorexant on sleep and daytime functioning in patients with insomnia during 3 months of treatment, the risks of withdrawal symptoms and rebound insomnia were evaluated at treatment cessation. Methods In two randomized, double-blind, 3-month trials, adult (18–64 years) and elderly (≥65) patients with insomnia were assigned (1:1:1) to receive oral daridorexant 25mg, 50mg or placebo (Trial-1, NCT03545191) or 10mg, 25mg or placebo (Trial-2, NCT03575104) every evening. Each trial included a 7-day, single-blind, placebo run-out period following double-blind treatment to evaluate withdrawal symptoms and rebound insomnia. Withdrawal effects were assessed by the change in Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ) total score, from last assessment on double-blind treatment to end of placebo run-out, and occurrence of relevant adverse events (AEs). Rebound insomnia was assessed objectively by change in wake-after-sleep-onset (WASO) and latency-to-persistent sleep (LPS), from baseline to first night of placebo run-out, and by subjective total-sleep-time (sTST), from baseline to end of run-out (mean of 7-days). Analyses included all patients who received ≥1 dose of placebo run-out treatment (Trial-1: N=852; Trial-2: N=851). Results No increase in mean BSWQ score from last assessment on double-blind treatment to end of placebo run-out was reported (Trial-1: 25mg, -0.6±2.3; 50mg, -0.6±2.3; placebo, -0.7±2.3; Trial-2: 10mg, -0.5±2.6; 25mg, -0.4±1.9; placebo, -0.4±1.4). No patients had a BWSQ score >20 at end of run-out. No AEs suggestive of withdrawal symptoms were reported. Mean WASO and LPS values (min) decreased from baseline to placebo run-out (WASO Trial-1: 25mg, -8.6±55.5; 50mg, -2.5±52.4; placebo, -20.4±45.8; Trial-2: 10mg, -11.6±58.3; 25mg, -5.1±57.9; placebo, -26.2±53.5; LPS Trial-1: 25mg, -17.2±56.7; 50mg, -15.0±55.8; placebo, -27.8±47.2; Trial-2: 10mg, -17.3±67.2; 25mg, -10.3±67.3; placebo, -18.3±63.8) while sTST values (min) increased (Trial-1: 25mg, 43.3±53.8; 50mg, 42.9±59.6; placebo, 42.3±52.7; Trial-2: 10mg, 43.3±52.9; 25mg, 46.8±55.4; placebo, 42.3±53.8) indicating absence of rebound effects. Conclusion Treatment with daridorexant for up to 3-months was not associated with any evidence of drug withdrawal or rebound insomnia upon abrupt discontinuation, indicating no safety concerns for patients should treatment be stopped. Support (if any) Funded by Idorsia Pharmaceuticals Ltd.

Avoiding Adverse Drug Withdrawal Events When Stopping Unnecessary Medications According to the STOPPFrail Criteria

OBJECTIVE: To provide clinicians with information about avoiding adverse drug withdrawal events (ADWEs) when discontinuing unnecessary medications as per the STOPPFrail criteria. DATA SOURCES: Searches of MEDLINE (1970-June 2020), the Cochrane Database of Systematic Reviews (through June 2020), Google Scholar (through June 2020). STUDY SELECTiON: Reviews and original studies of ADWEs. DATA EXTRACTiON: Tapering protocols for specific drugs/ classes from randomized controlled deprescribing trials. DATA SYNTHESiS: Six drug classes were identified as being high risk for physiological ADWEs. CONCLUSiON: The occurrence of ADWEs is rare in comparison to adverse drug reactions in older adults. Few drugs/classes have been reported to have physiological ADWEs with abrupt discontinuation. For these we provide information about tapering protocols and symptom monitoring to avoid ADWEs.