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. 2025 Mar 18:15:100325.
doi: 10.1016/j.dadr.2025.100325. eCollection 2025 Jun.

Influence of SSRI and SNRI co-prescription on benzodiazepine prescription trajectories

Kerry L Kinney  1 , Eliseu da Cruz Moreira-Junior  2 , Laís F Berro  2 , Matthew C Morris  2   3 , James K Rowlett  2
Affiliations

Influence of SSRI and SNRI co-prescription on benzodiazepine prescription trajectories

Kerry L Kinney et al. Drug Alcohol Depend Rep. .

Abstract

Purpose: This study examined whether co-prescription of selective serotonin reuptake inhibitors (SSRIs) or serotonin or norepinephrine reuptake inhibitors (SNRI)s with benzodiazepines is associated with differences in benzodiazepine prescriptions both within individual patients over time and between patients.

Methods: We analyzed deidentified electronic health records of patients prescribed a benzodiazepine between 2020 and 2022 (N = 847). Patients were categorized into three groups: those co-prescribed an SSRI, those co-prescribed an SNRI, and those not co-prescribed an SSRI or SNRI.

Results: Individuals co-prescribed an SSRI (M=6.63) or an SNRI (M=8.31) had more benzodiazepine prescription encounters than those who were not co-prescribed an SSRI/SNRI (M=5.08). Individuals co-prescribed an SSRI or SNRI also received a higher maximum benzodiazepine dosage than those who were not co-prescribed an SSRI/SNRI (SSRI M=2.41; SNRI M=2.30; No SSRI/SNRI M=1.91 diazepam milligram equivalent defined daily doses). Multilevel models indicated the SSRI co-prescription group received a higher initial benzodiazepine dosage (b=0.394), but showed no significant change in benzodiazepine dosage over time. When controlling for demographic and clinical correlates of benzodiazepine prescriptions, those who were not co-prescribed an SSRI showed an increase in benzodiazepine dose over time (b=0.075). Multilevel models revealed no relationship between SNRI co-prescription and starting benzodiazepine dosage or change in benzodiazepine dosage over time. An anxiety disorder diagnosis, younger age, and non-Black/African American race were associated with higher benzodiazepine dose.

Conclusions: Individuals who are co-prescribed an SSRI/SNRI may be vulnerable to longer treatment durations and higher prescribed doses of benzodiazepines, raising concerns about risk for dependence among individuals receiving combined benzodiazepine and SSRI/SNRI treatment.

Keywords: Benzodiazepine; Prescribing practices; Prescription; Selective serotonin reuptake inhibitor; Serotonin and norepinephrine reuptake inhibitor.

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Conflict of interest statement

The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Encounter flow diagram.
Fig. 2
Fig. 2
a) Number of benzodiazepine prescriptions, including refills, for patients prescribed a selective serotonin reuptake inhibitor (SSRI) plus a benzodiazepine (“SSRI” group), prescribed a serotonin and norepinephrine reuptake inhibitor (SNRI) plus a benzodiazepine (“SNRI” group), or benzodiazepine alone (“No SSRI/SNRI” group). b) Maximum benzodiazepine dosage for patients in the SSRI, SNRI, or no SSRI/SNRI group. Maximum dose is expressed as the diazepam milligram equivalent defined daily doses (DMEDDD) +  SEM. Data were analyzed with independent t-tests.
Fig. 3
Fig. 3
This figure illustrates a simple slope analysis of benzodiazepine (BZD) dosage (expressed as diazepam milligram equivalent defined daily dose, DMEDDD) across encounters in individuals prescribed a selective serotonin reuptake inhibitor (SSRI and individuals who were not prescribed an SSRI or SNRI.
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