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Off-label prescription of benzodiazepines: a retrospective cohort study of prescribing prevalence in primary care.

2025· preprint· en· W4407628895 on OpenAlexaffabout
Kevin Trimm, M Moraga, Bärbel Knaüper, Elham Rahme, Emily G. McDonald, Robyn Tamblyn

Bibliographic record

Venuenot available
Typepreprint
Languageen
FieldPsychology
TopicSleep and related disorders
Canadian institutionsMcGill University
Fundersnot available
KeywordsMedical prescriptionMedicinePrimary careRetrospective cohort studyCohortEmergency medicineCohort studyFamily medicineInternal medicinePharmacology

Abstract

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Background Benzodiazepines are commonly prescribed medications approved for and used in the treatment of anxiolytic and sleep disorders, as well as for seizures, and alcohol withdrawal. However, benzodiazepines are also controlled substances (schedule IV in Canada) because of their potential for abuse and personal harms, which are especially prevalent among older people. It is therefore important to understand how benzodiazepines are being prescribed, and the prevalence of off-label benzodiazepine prescribing, of which very little is known due to challenges in documenting treatment indication. Methods Data from the MOXXI (Medical Office of the XXIst century) electronic health record system in Quebec Canada was used, where specifying the treatment indication for each prescription is required, to estimate the prevalence of off-label prescribing and indications for off-label use of benzodiazepines. Each drug indication was retrospectively classified as either on-label or off-label according to the Health Canada drug database. Off-label prescriptions were further classified as having class evidence supporting their prescription if another benzodiazepine had been approved for the indication by Health Canada. Results There were 20,125 (17.0%) adult patients prescribed benzodiazepines out of the 118,227 patients enrolled in the MOXXI system. The patients were predominantly female (65.6%), and tended to be older with an average age of 60.14 years (standard deviation = 15.68) at the time of the first benzodiazepine prescription. A total of 101,583 unique prescriptions were written for 14 different benzodiazepines to these patients. An approximately equal number of benzodiazepines were prescribed on and off-label (49.3% on-label, 49.2% off-label), with clonazepam having the highest prevalence of off-label prescription (99.5%). Most off-label prescription indications were classified as having class evidence (95.2%). The most common off-label indication was insomnia; 31.6% of all off-label benzodiazepine prescriptions were for insomnia. Conclusions We found that benzodiazepines were frequently prescribed in the province of Quebec and were prescribed off-label approximately half of the time. When prescribed off-label we found that the majority of these prescriptions were for indications that were approved for at least one benzodiazepine. These findings indicate the importance of reminding physicians on the important differences between benzodiazepines that can substantially impact patient outcomes, particularly in older people.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.319
Threshold uncertainty score0.634

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.003
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.296
Teacher spread0.277 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes2
Has abstractyes

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