A nationwide register-based cohort study from Finland including 48 124 incident benzodiazepines and related drug (BZDR) users aged 18–65 years who initiated use in 2006 and were not dispensed BZDRs during 2004–2005. The follow-up was 5 years or until death, whichever occurred first.

To investigate sociodemographic and clinical factors associated with high-dose use of BZDRs (i.e. Z-drugs) among new BZDR users.

The temporal BZDR dose was calculated as a point estimate every 6 months after initiation as defined daily doses (DDDs) per day, based on the PRE2DUP method (an approach based on mathematical modelling of personal drug purchasing behaviours). Sociodemographic and clinical factors associated with dose categories were studied using multinomial logistic regression.

During the 5-year follow-up, very high-dose BZDR use was observed in 7.4% (n = 3557) and medium high-dose use in 25.5% (n = 12 266) of the users (corresponding to ≥30 mg and 10–29 mg in diazepam equivalents, respectively). Very high-dose use was more common among men compared with women (10.9% versus 4.6%). Very high-dose use patterns were especially observed in younger age groups (18- to 25-year-olds). Compared with oxazepam, initiating BZDR use with clonazepam (adjusted odds ratio 3.86, 95% CI 3.24–4.60), diazepam (2.05, 1.78–2.36) or alprazolam (1.76, 1.52–2.03) was associated with increased odds for very high-dose use. Both medium high-dose and very high-dose BZDR use were associated with a lower level of education. In all, 58% of very high-dose use occurred in BZDR users who received their first prescription from general practitioners.

Clinicians should be aware of the dose escalation risk especially when prescribing diazepam, alprazolam or clonazepam for psychiatric indications. If BZDRs are needed, our findings suggest favouring oxazepam.

Benzodiazepines (BZDs) and related drugs (BZRDs) are widely used to reduce agitation, anxiety and sleep disturbances in the elderly, despite concerns raised about their modest efficacy for such indications and risk of severe adverse effects, including acute consequences on cognition. Recently, some studies have also raised concerns about the long-term effect of BZDs, suggesting their association with an increased risk of cognitive decline and dementia.

To review published synthesis studies on the risk of dementia development due to BZDs/BZRDs use.

An electronic search was conducted in PubMed. Meta-analysis, systematic and non-systematic reviews examining the association between BZDs/BZRDs and subsequent dementia were included. No language nor publication date restrictions were applied. Search results other than synthesis studies were excluded. Studies were screened for relevance based on predefined inclusion and exclusion criteria.

Overall, 246 results were obtained. After initial screening, nine studies were included. From these, three were systematic reviews with meta-analysis of observational studies (cohort and/or case-control), one was a systematic review from observational studies and five were non-systematic reviews. Most studies found an association between BZDs/BZRDs and subsequent dementia, with meta-analysis studies reporting an increased risk (OR) between 1,38 and 1,78, even after controlling for protopathic bias. However, difficulties in establishing a causal relationship are reported due to the considerable clinical and methodological heterogeneity of the primary studies.

Most studies suggest an association between the use of BZDs/BZRDs and dementia risk, highlighting that their prescription should be cautious, prevented or reduced to attenuate this risk.