Add-on benzodiazepine treatment in patients with major depressive disorder – results from a European cross-sectional multicenter study

Markus Dold, Lucie Bartova, Gernot Fugger, Marleen Margret Mignon Mitschek, Alexander Kautzky, Richard Frey, Stuart Montgomery, Joseph Zohar, Julien Mendlewicz, Daniel Souery, Chiara Fabbri, Alessandro Serretti, Siegfried Kasper

Research output: Contribution to journalArticlepeer-review


Since many patients with major depressive disorder (MDD) do not satisfactorily respond to initial antidepressant monotherapy, add-on treatment strategies with other psychiatric compounds are often established. The present European multicenter cross-sectional study comprising 1410 MDD in- and outpatients investigated the prescription pattern of benzodiazepines as add-on treatment in the psychopharmacotherapy of MDD. Analyses of variance, chi-squared tests, and logistic regression analyses were conducted to examine differences in socio-demographic, clinical, and treatment characteristics between benzodiazepine users and non-users. The prescription rate for adjunctive benzodiazepine treatment amounted to 31.35%. The most often administered benzodiazepines were lorazepam (11.13%), clonazepam (6.74%), and alprazolam (6.60%). Benzodiazepine users exhibited more severe depressive symptoms expressed by a higher mean Montgomery and Åsberg Depression Rating Scale total score at study entry (26.92 ± 11.07 vs 23.55 ± 11.23, p<.0001) and at the beginning of the current major depressive episode (35.74 ± 8.08 vs 33.31 ± 7.40, p<.0001). Furthermore, they were characterized by a higher proportion of patients receiving additional augmentation/combination medications with antidepressants (40.95% vs 24.28%, p<.0001), antipsychotics (41.63% vs 18.39%, p<.0001), and low-potency antipsychotics (10.18% vs 4.75%, p<.0001). Moreover, benzodiazepine prescription was associated with older age, unemployment, inpatient treatment, suicide risk, psychotic and melancholic features, comorbid panic disorder, agoraphobia, social phobia, and obsessive-compulsive disorder. Taken together, our findings indicate that benzodiazepine augmentation in MDD is first of all established in severe/difficult-to-treat conditions and serves as predictor for the use of additional augmentation/combination treatment strategies.

Original languageEnglish
Pages (from-to)70-80
Number of pages11
JournalEuropean Neuropsychopharmacology
StatePublished - Dec 2020
Externally publishedYes


  • Antidepressants
  • Augmentation/combination treatment
  • Benzodiazepines
  • Major depressive disorder
  • Treatment resistant depression
  • Treatment response


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