Brief Motivational Intervention (BMI) on the Deprescription of Benzodiazepines and Related Substances in Adult Chronic Drug Users

Official title

Impact of Identification and Brief Motivational Intervention in Dispensing Pharmacies (BMI) on the Deprescription of Benzodiazepines and Related Substances in Adult Chronic Drug Users

Overview

We hypothesise that a short-term intervention by dispensing pharmacists is feasible and relatively easy to implement, and that it could have an impact on the deprescribing of BZD/Z in adult patients. Two primary objectives will be evaluated in a sequential hierarchical manner, with two primary endpoints analysed one after the other, without alpha risk adjustment, but the second can only be analysed if the null hypothesis is rejected for the first: 1. Evaluate the impact of brief motivational intervention (BMI) on reducing the daily dose of BZD/Z prescribed at 6 months (superiority hypothesis) compared with the usual practice of dispensing BZD/Z in pharmacies. 2. Evaluate the impact of BMI on clinical worsening at 6 months (non-inferiority hypothesis) in comparison with the usual practice of dispensing BZD/Z in pharmacies.

Detailed description

In France, the prevalence of use of benzodiazepines (BZDs) and related drugs (Z-drugs: zolpidem, zopiclone) (BZD/Z) was estimated at 13.4% in 2015, and 15% of new users had a first prescription exceeding the legal duration. The increase in prescriptions has continued to grow: in the first 4 months of 2021, an increase of 1.3 million anxiolytic treatments and 580,000 hypnotic treatments was observed, with new prescriptions for these treatments increasing by 15% for anxiolytics and 26% for hypnotics over the same year. The prevalence of long-term (\>6 months) BZD prescriptions varies from country to country between 6% and 15% in the general population, and is estimated to reach 22% to 55% in people aged ≥ 65 years. In France, recommendations and good practice guidelines recommend prescriptions limited to 4 weeks for hypnotic BZD/Z and 12 weeks for anxiolytic BZD. However, a recent study focusing solely on anxiolytic BZDs, carried out in patients covered by the general social security system (excluding special schemes such as self-employed workers, farmers, etc.), showed that 12.2% of women and 9.3% of men aged over 50 were prescribed for longer than the legal duration.

All countries agree on the need to limit the length of time these drugs are prescribed because of the rapid inversion of the benefit/risk ratio in the case of prolonged and continuous prescribing (rapid loss of efficacy due to the tolerance effect associated with the occurrence of adverse effects.

A number of public health initiatives have been taken in France to reduce the initiation or continued use of long-term BZD/Z prescriptions, including information for healthcare professionals about the risks, pictograms on drug packaging, directives from the health authorities, incentives offered by the Assurance Maladie and regulatory measures to control prescribing. Alongside these measures, various types of psychosocial intervention are specifically aimed at deprescribing, defined as a clinically supervised process of stopping or reducing the dose of drugs when they cause harm or when the potential risks outweigh the benefits. These strategies have been evaluated for several years, ranging from brief interventions in the form of letters, self-support manuals and targeted consultations, to more complex psychotherapeutic interventions such as cognitive behavioural therapy (CBT) or pharmacological interventions.

Although complex interventions such as structured educational programmes or 3rd wave CBT have been shown to be effective in reducing long-term BZD/Z use, particularly in the elderly, they are often too long and complex to be implemented on a large scale, particularly in primary care, and all the more so in a context of increasing shortage of specialists. Brief interventions, which are both more realistic and functional, have been shown to be effective in reducing and stopping long-term use of BZD/Z at 6 and 12 months post-intervention. At the same time, very few studies have involved the active participation of pharmacy professionals. Yet the involvement of pharmacists would optimise prescribing, and a simple psychoeducation action carried out in pharmacies would have an economic impact. With a view to the shift to ambulatory care centred on the structuring of care pathways, increasing the skills of local pharmacists, as part of a multiprofessional coordination strategy, is a response to the requirements of the law modernising the French healthcare system, while offering a simple and pragmatic intervention model for patients whose prescriptions need to be optimised.

In this study, the investigators propose to evaluate the impact of identification combined with a brief motivational intervention in pharmacies (BMI) targeting the deprescription of BZD/Z in adult patients with long-term prescriptions (≥ 6 months).

Interventions

• Other Brief motivational intervention
  identification followed by a brief motivational intervention in pharmacies (BMI) based on the mobilisation of patients' psychosocial skills and the integration of tools to help reduce consumption of BZD/Z prescribed over the long term (≥ 6 months).

Primary outcome measures

• Change of the Daily dose of BZD/Z drug [Time frame: 6 months]
• Worsening of the clinical symptoms of anxiety and/or sleep disorders [Time frame: 6 months]

Secondary outcome measures (9)

• change of the prescribed daily dose of BZD/Z without clinical worsening (superiority hypothesis) compared with the usual practice of dispensing BZD/Z in pharmacies [Time frame: 12 months]
• complete cessation of BZD/Z prescriptions without clinical worsening (superiority hypothesis) compared with the usual practice of dispensing BZD/Z in pharmacies [Time frame: 6 months and 12 months]
• declared consumption compared with the usual practice of dispensing BZD/Z in pharmacies [Time frame: 6 months and 12 months]
• anxiety symptoms [Time frame: 12 months]
• depressive symptoms [Time frame: 6 and 12 months]
• Worsening of severity of insomnia [Time frame: 12 months]
• transfers to other addictive products or behaviours [Time frame: 6 and 12 months]
• misuse of BZD/Z [Time frame: 6 and 12 months]
• Adverse events description [Time frame: 3, 6, 9 and 12 months]

Eligibility criteria

Inclusion criteria

• Continuous treatment (at least once daily) with BZD/Z for at least 6 months, after verification of 6 months' supply.
• Signed informed consent
• Patient able to understand the survey and complete a questionnaire in French.
• Affiliation with the French social security system

Exclusion criteria

• Concomitant treatment with:

• The following oral antipsychotics: risperidone, olanzapine, aripiprazole, quetiapine, clozapine, haloperidol, flupentixol, pimozide, chlorpromazine, sulpiride, zuclopenthixol, loxapine, cyamemazine (>100mg/D), sulpiride (>150mg/D),
• Injectable medium- and long-acting antipsychotics
• Thymoregulatory treatment with lithium
• Treatments for alcohol use disorders: baclofen, nalmefene, naltrexone, acamprosate, disulfiram
• Opiate substitution treatments: buprenorphine, methadone
• Anti-epileptic drugs
• History of convulsions or epilepsy
• History of gabaergic withdrawal accidents: delirium tremens, confusional syndrome requiring specialist treatment (hospitalisation, specialist consultation), epileptic seizures, etc.
• Patients suffering from cancer
• Persons referred to in articles L1121-5 to L1121-8 of the French Public Health Code (corresponding to all protected persons: pregnant women, women in childbirth, nursing mothers, persons deprived of their liberty by judicial or administrative decision, persons subject to a legal protection measure).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Health services research

Study locations

France · 20 centers

• Pharmacie Riffard Annonay — Annonay
• Pharmacie du Village — Auriol
• Pharmacie des Champs Dolent — Beauvais
• Pharmacie Troisgros — Cap-d'Ail
• Pharmacie des Fontanilles — Castelnaudary
• Pharmacie Dolus d'Oléron — Dolus-d'Oléron
• Pharmacie de Dommartin — Dommartin
• Pharmacie du Mont Guillaume — Embrun
• … and 12 more centers

Publications

• Victorri-Vigneau C, Laforgue EJ, Grall-Bronnec M, Guillou-Landreat M, Rousselet M, Guerlais M; FAN-Network; Feuillet F, Jolliet P. Are Seniors Dependent on Benzodiazepines? A National Clinical Survey of Substance Use Disorder. Clin Pharmacol Ther. 2021 Feb;109(2):528-535. doi: 10.1002/cpt.2025. Epub 2020 Sep 23. PMID 32860424
• Chapoutot M, Peter-Derex L, Bastuji H, Leslie W, Schoendorff B, Heinzer R, Siclari F, Nicolas A, Lemoine P, Higgins S, Bourgeois A, Vallet GT, Anders R, Ounnoughene M, Spencer J, Meloni F, Putois B. Cognitive Behavioral Therapy and Acceptance and Commitment Therapy for the Discontinuation of Long-Term Benzodiazepine Use in Insomnia and Anxiety Disorders. Int J Environ Res Public Health. 2021 Sep 2 PMID 34639523
• Cheng JS, Huang WF, Lin KM, Shih YT. Characteristics associated with benzodiazepine usage in elderly outpatients in Taiwan. Int J Geriatr Psychiatry. 2008 Jun;23(6):618-24. doi: 10.1002/gps.1950. PMID 18058834
• Kurko TA, Saastamoinen LK, Tahkapaa S, Tuulio-Henriksson A, Taiminen T, Tiihonen J, Airaksinen MS, Hietala J. Long-term use of benzodiazepines: Definitions, prevalence and usage patterns - a systematic review of register-based studies. Eur Psychiatry. 2015 Nov;30(8):1037-47. doi: 10.1016/j.eurpsy.2015.09.003. Epub 2015 Nov 4. PMID 26545257
• Preville M, Bosse C, Vasiliadis HM, Voyer P, Laurier C, Berbiche D, Perodeau G, Grenier S, Beland SG, Dionne PA, Gentil L, Moride Y. Correlates of potentially inappropriate prescriptions of benzodiazepines among older adults: results from the ESA study. Can J Aging. 2012 Sep;31(3):313-22. doi: 10.1017/S0714980812000232. Epub 2012 Jul 17. PMID 22800936
• Airagnes G, Lemogne C, Olekhnovitch R, Roquelaure Y, Hoertel N, Goldberg M, Limosin F, Zins M. Work-Related Stressors and Increased Risk of Benzodiazepine Long-Term Use: Findings From the CONSTANCES Population-Based Cohort. Am J Public Health. 2019 Jan;109(1):119-125. doi: 10.2105/AJPH.2018.304734. Epub 2018 Nov 29. PMID 30495993
• Vinkers CH, Olivier B. Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-Selective GABA(A) Receptor Modulators? Adv Pharmacol Sci. 2012;2012:416864. doi: 10.1155/2012/416864. Epub 2012 Mar 29. PMID 22536226
• Morin CM, Colecchi C, Stone J, Sood R, Brink D. Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial. JAMA. 1999 Mar 17;281(11):991-9. doi: 10.1001/jama.281.11.991. PMID 10086433

Identifiers

NCT: NCT06446349 · 38RC23.0198 · 2023-A01747-38

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗